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A Study Of PF-05212384 Plus Irinotecan Vs Cetuximab Plus Irinotecan In Patients With KRAS And NRAS Wild Type Metastatic Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT01925274
Recruitment Status : Terminated (Enrollment to the study was terminated on 11Nvo2014 due to slow recruitment. There were no safety or efficacy issues that contributed to this decision.)
First Posted : August 19, 2013
Results First Posted : April 27, 2017
Last Update Posted : January 8, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Colorectal Cancer
Interventions Drug: PF-05212384
Drug: irinotecan
Drug: Cetuximab
Drug: Irinotecan
Enrollment 19
Recruitment Details  
Pre-assignment Details  
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%). Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities. PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Period Title: Overall Study
Started 7 6 6
Completed 0 0 0
Not Completed 7 6 6
Reason Not Completed
Death             1             0             0
Lost to Follow-up             0             1             0
Withdrawal by Subject             1             2             0
Study terminated by sponsor             4             0             0
Protocol amendment             1             3             6
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC) Total
Hide Arm/Group Description PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%). Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities. PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%). Total of all reporting groups
Overall Number of Baseline Participants 7 6 6 19
Hide Baseline Analysis Population Description
The baseline analysis population included all enrolled participants who received the study drug.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 7 participants 6 participants 6 participants 19 participants
<18 years 0 0 0 0
18-64 years 5 4 4 13
>=65 years 2 2 2 6
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 6 participants 6 participants 19 participants
Female
4
  57.1%
3
  50.0%
4
  66.7%
11
  57.9%
Male
3
  42.9%
3
  50.0%
2
  33.3%
8
  42.1%
1.Primary Outcome
Title Progression Free Survival (PFS) as Assessed by Investigators
Hide Description Progression-free survival (PFS) was the time from the first dose of study treatment to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Objective progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. Median PFS was estimated based on the Kaplan-Meier method.
Time Frame From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized, with KRAS (Kirsten ras oncogene) and NRAS (neuroblastoma ras viral oncogene homolog) wild type status confirmed by central lab, and with treatment arm assignment designated according to randomization. As pre-specified in the protocol, this outcome measure was not analyzed for Japanese Lead-In Cohort.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
Overall Number of Participants Analyzed 4 3
Median (95% Confidence Interval)
Unit of Measure: months
3.7
(1.5 to 7.4)
NA [1] 
(NA to NA)
[1]
Less than 50% of the population experienced an event, therefore, median and 95% confidence interval were not calculated. The only individual value was 16.6 months.
2.Secondary Outcome
Title Number of Participants With Unacceptable Toxicity in Cycle 1 (Japanese LIC Only)
Hide Description Unacceptable toxicity (according to Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0) was any of the following occurrences: (1) Grade 4 neutropenia >7 days, or febrile neutropenia, or Grade 4 thrombocytopenia; (2) Grade >=3 nausea/vomiting despite optimal antiemetic treatment, or Grade >=3 diarrhea despite optimal anti diarrheal treatment; (3) unmanageable Grade >=3 hyperglycemia; (4) mean QTc interval (time from electrocardiogram [ECG] Q wave to the end of the T wave corresponding to electrical systole, corrected for heart rate) >501 msec in triplicate 12-lead ECG, or myocardial infarction, or ventricular arrhythmia; (5) Grade >=3 non-hematologic toxicity; (6) treatment delay of >=2 weeks due to study drug related toxicity; (7) persistent, intolerable toxicities which resulted in failure to deliver at least 75% of doses of both PF-05212384 and irinotecan during Cycle 1; (8) Grade >=2 respiratory toxicities.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants enrolled into Japanese LIC. As pre-specified in protocol, this outcome measure was not analyzed for reporting arms: “PF-05212384 + Irinotecan: Arm A” and “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: participants
0
3.Secondary Outcome
Title Percentage of Participants With Objective Response
Hide Description Percentage of participants with objective response was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1. Confirmed PR was defined as disappearance of all target lesions. Confirmed PR was defined as >=30% decrease in sum of the longest dimensions of the target lesions taking the baseline sum as a reference. Confirmed responses were those that persisted on repeat imaging study >=4 weeks after initial documentation of response.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Response evaluable analysis set was used for the analysis of objective response, and it included all participants in the full analysis set (all participants who were randomized, with treatment arm assignment designated according to randomization) who had an adequate baseline assessment of disease and measurable disease.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6 6
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
14.3
(0.4 to 57.9)
50.0
(11.8 to 88.2)
0
(0.0 to 45.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-05212384 + Irinotecan: Arm A, Cetuximab + Irinotecan: Arm B
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -35.71
Confidence Interval (2-Sided) 95%
-83.4 to 12.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Duration of Response
Hide Description For participants with an objective response (CR or PR), duration of response was defined as the time from first documentation of CR or PR to date of first documentation of objective progression or death. Date of first documentation of progression and date of first documentation of CR or PR were based on Investigator's assessment of response.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who achieved CR or PR in Arm A and Arm B. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm “PF 05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
Overall Number of Participants Analyzed 1 3
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [2] 
(NA to NA)
[1]
Only 1 participant achieved CR or PR, therefore, median and 95% confidence interval were not calculated. The only individual value was 5.6 months.
[2]
Less than 50% of the population experienced subsequent progression or death, therefore, median and 95% confidence interval were not calculated. The only individual value was 14.8 months.
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival (OS) was defined as the duration from enrollment to death. Participants last known to be alive were censored at date of last contact.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol analysis set, i.e. all participants who were randomized, with KRAS and NRAS wild type status confirmed by central lab and with treatment arm assignment designated according to randomization. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm “PF 05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
Overall Number of Participants Analyzed 4 3
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(3.3 to NA)
NA [2] 
(NA to NA)
[1]
Median was not calculated, since less than 50% of population died.
[2]
No death occurred in this arm.
6.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Hide Description An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE was defined as any untoward occurrence at any dose that resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. AEs included both serious and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study drug.
Time Frame Administration of the first dose of study drug through 28 calendar days after the last administration of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study treatment, with treatment arm assignment designated according to actual study treatment received.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6 6
Measure Type: Number
Unit of Measure: participants
AEs 7 6 6
SAEs 3 1 1
7.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Common Terminology Criteria for Adverse Events (CTCAE) Grade
Hide Description TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. CTCAE version 4.0 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE.
Time Frame Administration of the first dose of study drug through 28 calendar days after the last administration of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study treatment, with treatment arm assignment designated according to actual study treatment received.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6 6
Measure Type: Number
Unit of Measure: participants
Grade 1 1 2 2
Grade 2 1 1 0
Grade 3 3 2 4
Grade 4 2 0 0
Grade 5 0 1 0
8.Secondary Outcome
Title Number of Participants With Laboratory Test (Hematology) Abnormalities
Hide Description The following hematology parameters were evaluated in this study: hemoglobin, white blood cells (WBC) with differential, and platelets.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study treatment, with treatment arm assignment designated according to actual study treatment received.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6 6
Measure Type: Number
Unit of Measure: participants
Anemia 6 6 6
Hemoglobin increased 0 0 0
Lymphocyte count increased 0 2 0
Lymphopenia 5 4 5
Neutrophils (absolute) 4 3 5
Platelets 0 3 1
White blood cells 4 4 5
9.Secondary Outcome
Title Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hide Description The following chemistry parameters were evaluated in this study: sodium, potassium, magnesium, chloride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, albumin, blood urea nitrogen (BUN) or urea, creatinine, total calcium, glycosylated hemoglobin (HbA1c), glucose, uric acid, phosphorus or phosphate, insulin, and C-peptide.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study treatment, with treatment arm assignment designated according to actual study treatment received.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6 6
Measure Type: Number
Unit of Measure: participants
ALT 2 1 1
Alkaline phosphatase 3 4 4
AST 2 1 1
Total bilirubin 0 1 0
Creatitine 4 3 6
Hypercalcemia 1 0 0
Hyperglycemia 6 4 4
Hyperkalemia 1 0 0
Hypermagnesemia 0 0 0
Hypernatremia 1 0 1
Hypoalbuminemia 2 4 4
Hypocalcemia 2 3 3
Hypoglycemia 0 1 0
Hypokalemia 2 2 3
Hypomagnesemia 3 4 1
Hyponatremia 2 1 0
Hypophosphatemia 2 1 0
10.Secondary Outcome
Title Number of Participants With Laboratory Test (Urinalysis) Abnormalities
Hide Description Urinalysis included urine dipstick for protein and blood: if positive, perform a microscopic analysis. Number of participants with urine protein tested positive is presented.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study treatment, with treatment arm assignment designated according to actual study treatment received.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6 6
Measure Type: Number
Unit of Measure: participants
3 1 4
11.Secondary Outcome
Title Number of Participants With Laboratory Test (Coagulation) Abnormalities
Hide Description Coagulation analysis included partial thromboplastin time (PTT) and international normalized ratio (INR) or prothrombin time (PT).
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study treatment, with treatment arm assignment designated according to actual study treatment received.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6 6
Measure Type: Number
Unit of Measure: participants
PTT (number of participants =7, 6, 5) 2 4 0
PT (number of participants =7, 5, 6) 3 3 1
PT INR 1 2 2
12.Secondary Outcome
Title Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
Hide Description The number of participants with ECG post-baseline maximum absolute values meeting the following criteria was reported: (1) maximum QTc interval ranged from 450 to 480 msec; >480-500 msec; >500 msec; (2) maximum QTcB (QT corrected for heart rate using Bazett’s formula) interval ranged from 450 to 480 msec; >480-500 msec; >500 msec; (3) maximum QTcF (QT corrected for heart rate using Fridericia’s formula) interval ranged from 450 to 480 msec; >480-500 msec; >500 msec.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
QTc analysis set included all participants in the safety analysis set who had at least one ECG assessment after receiving study treatment.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 6 3 6
Measure Type: Number
Unit of Measure: participants
Maximum QTc interval: 450-480 msec 2 1 1
Maximum QTc interval: >480-500 msec 0 0 0
Maximum QTc interval: >500 msec 0 0 0
Maximum QTcB interval: 450-480 msec 3 1 0
Maximum QTcB interval: >480-500 msec 0 0 0
Maximum QTcB interval: >500 msec 0 0 0
Maximum QTcF interval: >450-480 msec 1 0 0
Maximum QTcF interval: >480-500 msec 0 0 0
Maximum QTcF interval: >500 msec 0 0 0
13.Secondary Outcome
Title Number of Participants With ECG Maximum Increase From Baseline Meeting Pre-defined Criteria
Hide Description

The number of participants with ECG maximum increase from baseline meeting the following criteria was reported:

Criterion A: maximum QTc interval increase from baseline >30 msec and ≤60 msec; criterion B: maximum QTc interval increase from baseline >60 msec; criterion C: maximum QTcB interval increase from baseline >30 msec and ≤60 msec; criterion D: maximum QTcB interval increase from baseline >60 msec; criterion E: maximum QTcF interval increase from baseline >30 msec and ≤60 msec; criterion F: maximum QTcF interval increase from baseline >60 msec.

Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
QTc analysis set included all participants in the safety analysis set who had at least one ECG assessment after receiving study treatment.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 6 3 6
Measure Type: Number
Unit of Measure: participants
Criterion A 1 1 0
Criterion B 0 0 0
Criterion C 0 1 0
Criterion D 0 0 0
Criterion E 0 0 0
Criterion F 0 0 0
14.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of PF-05212384
Hide Description Cmax of PF-05212384 was observed directly from data.
Time Frame Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9 and Cycle 1 Day 16.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic concentration analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one time point with a concentration measurement recorded. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1 Day 9
8345
(19%)
8534
(10%)
Cycle 1 Day 16 (number of participants =5, 6)
10120
(27%)
9670
(26%)
15.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Irinotecan
Hide Description Cmax of irinotecan was observed directly from data.
Time Frame Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic concentration analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one time point with a concentration measurement recorded. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1 Day 1
2283
(30%)
2123
(18%)
Cycle 2 Day 1 (number of participants =4, 5)
1620
(41%)
1999
(13%)
16.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of SN-38
Hide Description SN-38 is an irinotecan metabolite. Cmax of SN-38 was observed directly from data.
Time Frame Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic concentration analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one time point with a concentration measurement recorded. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1 Day 1
23.51
(32%)
24.25
(50%)
Cycle 2 Day 1 (number of participants =4, 5)
22.81
(67%)
28.04
(33%)
17.Secondary Outcome
Title Time for Maximum Plasma Concentration (Tmax) of PF-05212384
Hide Description Tmax of PF-05212384 was observed directly from data as time of first occurrence.
Time Frame Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9 and Cycle 1 Day 16.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 6 6
Median (Full Range)
Unit of Measure: hours
Cycle 1 Day 9
0.483
(0.467 to 0.517)
0.483
(0.467 to 0.500)
Cycle 1 Day 16 (number of participants =5, 6)
0.500
(0.467 to 0.517)
0.500
(0.483 to 0.517)
18.Secondary Outcome
Title Time for Maximum Plasma Concentration (Tmax) of Irinotecan
Hide Description Tmax of irinotecan was observed directly from data as time of first occurrence.
Time Frame Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6
Median (Full Range)
Unit of Measure: hours
Cycle 1 Day 1
1.50
(1.47 to 1.62)
1.53
(1.48 to 1.58)
Cycle 2 Day 1 (number of participants =4, 5)
1.55
(1.50 to 2.05)
1.53
(1.50 to 1.57)
19.Secondary Outcome
Title Time for Maximum Plasma Concentration (Tmax) of SN-38
Hide Description SN-38 is an irinotecan metabolite. Tmax of SN-38 was observed directly from data as time of first occurrence.
Time Frame Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6
Median (Full Range)
Unit of Measure: hours
Cycle 1 Day 1
2.00
(1.50 to 2.18)
1.98
(1.48 to 2.08)
Cycle 2 Day 1 (number of participants =4, 5)
2.03
(1.53 to 3.98)
1.93
(1.90 to 2.00)
20.Secondary Outcome
Title Terminal Elimination Half Life (t½) of PF-05212384
Hide Description T½ was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Time Frame Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9 and Cycle 1 Day 16.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 6 6
Mean (Standard Deviation)
Unit of Measure: hours
Cycle 1 Day 9 37.65  (4.55) 37.78  (3.61)
Cycle 1 Day 16 (number of participants =4, 6) 35.10  (6.90) 36.07  (4.56)
21.Secondary Outcome
Title Terminal Elimination Half Life (t½) of Irinotecan
Hide Description T½ was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Time Frame Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6
Mean (Standard Deviation)
Unit of Measure: hours
Cycle 1 Day 1 5.547  (0.562) 5.255  (0.420)
Cycle 2 Day 1 (number of participants =4, 5) 5.293  (0.488) 5.344  (0.719)
22.Secondary Outcome
Title Terminal Elimination Half Life (t½) of SN-38
Hide Description T½ was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Time Frame Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 2 4
Mean (Standard Deviation)
Unit of Measure: hours
Cycle 1 Day 1 (number of participants =2, 3) NA [1]   (NA) 9.890  (0.811)
Cycle 2 Day 1 NA [2]   (NA) 8.840  (1.091)
[1]
These summary statistics were not calculated, as the number of participants being analyzed was fewer than 3, considered as non-reliable for analysis. The individual values of these two participants were 8.05 and 8.56 hours, respectively.
[2]
These summary statistics were not calculated, as the number of participants being analyzed was fewer than 3, considered as non-reliable for analysis. The individual values of these two participants were 8.44 and 8.74 hours, respectively.
23.Secondary Outcome
Title Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of PF-05212384
Hide Description AUClast refers to the area under plasma concentration time profile from time zero to the time for the last quantifiable concentration. AUClast of PF-05212384 was determined using linear/log trapezoidal method.
Time Frame Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
11530
(15%)
13390
(17%)
24.Secondary Outcome
Title Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of Irinotecan
Hide Description AUClast refers to the area under plasma concentration time profile from time zero to the time for the last quantifiable concentration. AUClast of irinotecan was determined using linear/log trapezoidal method.
Time Frame Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cycle 1 Day 1
11860
(23%)
11030
(29%)
Cycle 2 Day 1 (number of participants =4, 5)
8776
(62%)
10380
(29%)
25.Secondary Outcome
Title Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of SN-38
Hide Description AUClast refers to the area under plasma concentration time profile from time zero to the time for the last quantifiable concentration. AUClast of SN-38 (an irinotecan metabolite) was determined using linear/log trapezoidal method.
Time Frame Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cycle 1 Day 1
217.0
(29%)
217.9
(38%)
Cycle 2 Day 1 (number of participants =4, 5)
182.4
(43%)
228.5
(38%)
26.Secondary Outcome
Title Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05212384
Hide Description AUCinf refers to the area under plasma concentration time profile from time zero extrapolated to infinite time. AUCinf of PF-05212384 was calculated using the formula: AUCinf = AUClast + (Clast*/kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Time Frame Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
11700
(15%)
13580
(17%)
27.Secondary Outcome
Title Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Irinotecan
Hide Description AUCinf refers to the area under plasma concentration time profile from time zero extrapolated to infinite time. AUCinf of irinotecan was calculated using the formula: AUCinf = AUClast + (Clast*/kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Time Frame Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cycle 1 Day 1
12480
(23%)
11570
(30%)
Cycle 2 Day 1 (number of participants =4, 5)
9216
(63%)
10950
(31%)
28.Secondary Outcome
Title Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of SN-38
Hide Description AUCinf refers to the area under plasma concentration time profile from time zero extrapolated to infinite time. AUCinf of SN-38 (an irinotecan metabolite) was calculated using the formula: AUCinf = AUClast + (Clast*/kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Time Frame Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre specified in protocol, this outcome measure was not analyzed for reporting arm: “Cetuximab + Irinotecan: Arm B”.
Arm/Group Title PF-05212384 + Irinotecan: Arm A PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 2 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cycle 1 Day 1 (number of participants =2, 3)
NA [1] 
(NA%)
230.4
(13%)
Cycle 2 Day 1
NA [2] 
(NA%)
279.7
(45%)
[1]
These summary statistics were not calculated, as the number of participants being analyzed was fewer than 3, considered as non-reliable for analysis. The individual values of these two participants were 218 and 218 ng*hr/mL, respectively.
[2]
These summary statistics were not calculated, as the number of participants being analyzed was fewer than 3, considered as non-reliable for analysis. The individual values of these two participants were 120 and 215 ng*hr/mL, respectively.
29.Secondary Outcome
Title Levels of Signaling Proteins in Paired and Single Tumor Biopsies
Hide Description Pre defined signaling proteins included Akt (protein kinase B), p-Akt (phosphorylated Akt), p-S6 (phosphorylated ribosomal protein S6), p-Met (phosphorylated Met, a receptor tyrosine kinase), p-mTOR (phosphorylated mammalian target of rapamycin), EGFR (epithelial growth factor receptor), and p-EGFR (phosphorylated EGFR).
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Data for this outcome measure were not collected due to early termination of this study.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
30.Secondary Outcome
Title Number of Participants With Expression of Pre-defined Gene Sequences in Biopsied Tumor Tissues
Hide Description Pre-defined gene sequences were those related to EGFR, PI3K (phosphoinositide-3 kinase) and other oncogenic pathways; examples included but were not limited to PIK3CA (this gene encodes the catalytic subunit of PI3K), PIK3R1 (this gene encodes the regulatory subunit of PI3K), KRAS, NRAS and BRAF (this gene encodes serine/threonine-protein kinase B-Raf) sequences and PIK3CA gene amplification. Due to early termination of this study, these pre-defined gene sequences were not analyzed, except for KRAS and NRAS. Number of participants who had KRAS and NRAS wild type status confirmed by the central laboratory is presented.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants for whom at least one of these pre-defined gene sequences was analyzed were included.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Overall Number of Participants Analyzed 7 6 6
Measure Type: Number
Unit of Measure: participants
Confirmed wild type KRAS 4 3 6
Confirmed wild type NRAS 4 3 3
31.Secondary Outcome
Title Change From Baseline in Functional Assessment of Cancer Therapy-Colorectal (FACT-C)
Hide Description Functional Assessment of Cancer Therapy-Colorectal (FACT-C) was used in this study to assess Health-Related Quality of Life (HRQoL) and CRC-related symptoms in participants enrolled to the randomized portion of the study. The FACT-C is part of the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system, a comprehensive and extensive set of self-reported instruments for the assessment of health-related quality of life in participants with cancer or other chronic illnesses.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Data for this outcome measure were no longer collected after approval of protocol amendment 4, and data previously collected were insufficient to perform any analysis.
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B
Hide Arm/Group Description:
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Hide Arm/Group Description PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%). Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m^2 on Cycle 1 Day 1 followed by 250 mg/m^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities. PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28 day cycle) at a dose level of 180 mg/m^2. Both the dose levels of PF 05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
All-Cause Mortality
PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/7 (42.86%)   1/6 (16.67%)   1/6 (16.67%) 
Gastrointestinal disorders       
Colitis * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
General disorders       
Disease progression * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Infections and infestations       
Urinary tract infection * 1  0/7 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Nervous system disorders       
Transient ischaemic attack * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pneumothorax * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PF-05212384 + Irinotecan: Arm A Cetuximab + Irinotecan: Arm B PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/7 (100.00%)   6/6 (100.00%)   6/6 (100.00%) 
Blood and lymphatic system disorders       
Anaemia * 1  2/7 (28.57%)  3/6 (50.00%)  0/6 (0.00%) 
Leukopenia * 1  0/7 (0.00%)  0/6 (0.00%)  2/6 (33.33%) 
Neutropenia * 1  2/7 (28.57%)  1/6 (16.67%)  3/6 (50.00%) 
Cardiac disorders       
Sinus bradycardia * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Tachycardia * 1  1/7 (14.29%)  1/6 (16.67%)  0/6 (0.00%) 
Eye disorders       
Conjunctivitis allergic * 1  0/7 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Gastrointestinal disorders       
Abdominal discomfort * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Abdominal distension * 1  1/7 (14.29%)  1/6 (16.67%)  0/6 (0.00%) 
Abdominal pain * 1  3/7 (42.86%)  0/6 (0.00%)  0/6 (0.00%) 
Abdominal pain lower * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Abdominal pain upper * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Ascites * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Colitis * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Colonic fistula * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Constipation * 1  3/7 (42.86%)  3/6 (50.00%)  0/6 (0.00%) 
Diarrhoea * 1  5/7 (71.43%)  3/6 (50.00%)  3/6 (50.00%) 
Dry mouth * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Dyspepsia * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Anal incontinence * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Gingival bleeding * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Haemorrhoidal haemorrhage * 1  1/7 (14.29%)  1/6 (16.67%)  0/6 (0.00%) 
Haemorrhoids * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Nausea * 1  6/7 (85.71%)  3/6 (50.00%)  3/6 (50.00%) 
Stomatitis * 1  5/7 (71.43%)  1/6 (16.67%)  4/6 (66.67%) 
Vomiting * 1  4/7 (57.14%)  1/6 (16.67%)  2/6 (33.33%) 
General disorders       
Asthenia * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Chest pain * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Fatigue * 1  4/7 (57.14%)  2/6 (33.33%)  1/6 (16.67%) 
Influenza like illness * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Malaise * 1  0/7 (0.00%)  0/6 (0.00%)  2/6 (33.33%) 
Mucosal inflammation * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Oedema peripheral * 1  2/7 (28.57%)  1/6 (16.67%)  1/6 (16.67%) 
Pyrexia * 1  0/7 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Infections and infestations       
Anorectal infection * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Eye infection * 1  0/7 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Paronychia * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Rash pustular * 1  0/7 (0.00%)  2/6 (33.33%)  0/6 (0.00%) 
Upper respiratory tract infection * 1  1/7 (14.29%)  1/6 (16.67%)  0/6 (0.00%) 
Urinary tract infection * 1  1/7 (14.29%)  0/6 (0.00%)  1/6 (16.67%) 
Pneumonia * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Injury, poisoning and procedural complications       
Fall * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Laceration * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Skin abrasion * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Thermal burn * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Investigations       
Activated partial thromboplastin time prolonged * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Haemoglobin decreased * 1  0/7 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Neutrophil count decreased * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Weight decreased * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Blood alkaline phosphatase increased * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Platelet count decreased * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  3/7 (42.86%)  2/6 (33.33%)  3/6 (50.00%) 
Dehydration * 1  1/7 (14.29%)  1/6 (16.67%)  0/6 (0.00%) 
Diabetes mellitus * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Hyperglycaemia * 1  2/7 (28.57%)  0/6 (0.00%)  0/6 (0.00%) 
Hyperuricaemia * 1  2/7 (28.57%)  0/6 (0.00%)  0/6 (0.00%) 
Hypoalbuminaemia * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Hypocalcaemia * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Hypomagnesaemia * 1  1/7 (14.29%)  2/6 (33.33%)  0/6 (0.00%) 
Hypophosphataemia * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Hypokalaemia * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Back pain * 1  3/7 (42.86%)  1/6 (16.67%)  0/6 (0.00%) 
Muscle spasms * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Musculoskeletal chest pain * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Pain in extremity * 1  1/7 (14.29%)  0/6 (0.00%)  1/6 (16.67%) 
Nervous system disorders       
Dizziness * 1  3/7 (42.86%)  0/6 (0.00%)  0/6 (0.00%) 
Dysgeusia * 1  1/7 (14.29%)  1/6 (16.67%)  0/6 (0.00%) 
Headache * 1  3/7 (42.86%)  1/6 (16.67%)  0/6 (0.00%) 
Lethargy * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Neuropathy peripheral * 1  1/7 (14.29%)  1/6 (16.67%)  0/6 (0.00%) 
Psychiatric disorders       
Depression * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Insomnia * 1  0/7 (0.00%)  2/6 (33.33%)  1/6 (16.67%) 
Renal and urinary disorders       
Haematuria * 1  0/7 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Pollakiuria * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Renal failure * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Reproductive system and breast disorders       
Pelvic pain * 1  2/7 (28.57%)  0/6 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  1/7 (14.29%)  1/6 (16.67%)  0/6 (0.00%) 
Dry throat * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Dyspnoea * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Epistaxis * 1  1/7 (14.29%)  1/6 (16.67%)  1/6 (16.67%) 
Hiccups * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Hypoxia * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Oropharyngeal pain * 1  1/7 (14.29%)  0/6 (0.00%)  1/6 (16.67%) 
Pulmonary embolism * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Rhinitis allergic * 1  0/7 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Sinus congestion * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1  3/7 (42.86%)  2/6 (33.33%)  1/6 (16.67%) 
Dermatitis * 1  0/7 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Dermatitis acneiform * 1  0/7 (0.00%)  2/6 (33.33%)  0/6 (0.00%) 
Dry skin * 1  0/7 (0.00%)  2/6 (33.33%)  0/6 (0.00%) 
Nail disorder * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Pruritus * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Rash * 1  2/7 (28.57%)  1/6 (16.67%)  2/6 (33.33%) 
Rash pruritic * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Skin fissures * 1  0/7 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Vascular disorders       
Hypertension * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
Hypotension * 1  1/7 (14.29%)  0/6 (0.00%)  0/6 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 19.0
This study was terminated by sponsor due to strategic reasons and not due to any safety or efficacy concerns with treatment of PF-05212384.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01925274     History of Changes
Other Study ID Numbers: B2151005
2013-002095-40 ( EudraCT Number )
First Submitted: August 15, 2013
First Posted: August 19, 2013
Results First Submitted: January 9, 2017
Results First Posted: April 27, 2017
Last Update Posted: January 8, 2019