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Study of IMC-1121B in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT01005355
Recruitment Status : Completed
First Posted : October 30, 2009
Results First Posted : June 18, 2014
Last Update Posted : June 18, 2014
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Advanced Solid Tumors
Intervention Biological: IMC-1121B
Enrollment 15
Recruitment Details  
Pre-assignment Details A participant was considered to have completed the study if he or she completed the initial 6-week treatment period (Cycle 1) or if he or she discontinued therapy because of an IMC-1121B (ramucirumab)-related toxicity during Cycle 1.
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2) IMC-1121B 10 mg/kg (Cohort 3)
Hide Arm/Group Description

6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 3 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Period Title: Overall Study
Started 3 6 6
Received at Least 1 Dose of Study Drug 3 6 6
Completed 3 6 6
Not Completed 0 0 0
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2) IMC-1121B 10 mg/kg (Cohort 3) Total
Hide Arm/Group Description

6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 3 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Total of all reporting groups
Overall Number of Baseline Participants 3 6 6 15
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of study drug.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 6 participants 6 participants 15 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
3
 100.0%
6
 100.0%
4
  66.7%
13
  86.7%
>=65 years
0
   0.0%
0
   0.0%
2
  33.3%
2
  13.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 6 participants 6 participants 15 participants
Female
1
  33.3%
5
  83.3%
3
  50.0%
9
  60.0%
Male
2
  66.7%
1
  16.7%
3
  50.0%
6
  40.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Asian Number Analyzed 3 participants 6 participants 6 participants 15 participants
3 6 6 15
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 3 participants 6 participants 6 participants 15 participants
3 6 6 15
1.Primary Outcome
Title Number of Participants With Drug-Related Adverse Events
Hide Description Data presented are the number of participants who experienced adverse events (AE) of any grade, AE of Grade ≥3 based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v 3.0), serious adverse events (SAE) and AE resulting in death that was considered to be related to IMC-1121B (ramucirumab). A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Time Frame Baseline to study completion up to 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug.
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2) IMC-1121B 10 mg/kg (Cohort 3)
Hide Arm/Group Description:

6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 3 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 3 6 6
Measure Type: Number
Unit of Measure: participants
AE of any grade 3 6 6
AE of Grade ≥3 0 0 1
SAE 0 0 1
AE resulting in death 0 0 0
2.Primary Outcome
Title IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 1 and 2
Hide Description [Not Specified]
Time Frame Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Cohorts 1 and 2 who received study drug and had sufficient pharmacokinetics data to calculate Cmax for Cycles 1 and 2.
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2)
Hide Arm/Group Description:

6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 3 6
Mean (Standard Deviation)
Unit of Measure: micrograms/milliliter (mcg/mL)
Cycle 1 284  (63.7) 371  (113)
Cycle 2 (n=1, 2) 352 [1]   (NA) 694  (123)
[1]
Only 1 participant included in the analysis, therefore standard deviation is not calculable.
3.Primary Outcome
Title IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 3 to 5
Hide Description Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated.
Time Frame Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2)
Hide Arm/Group Description:

6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Primary Outcome
Title IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) Versus Time Curve - Cohorts 1 and 2 During Cycles 1 and 2
Hide Description AUC for Cycle 1 is AUC from time zero to infinity [AUC(0-∞)] and for Cycle 2 is AUC over a dosing interval (AUCτ).
Time Frame Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Cohorts 1 and 2 who received study drug and had sufficient pharmacokinetics data to calculate AUC(0-∞) for Cycle 1 and AUCτ for Cycle 2.
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2)
Hide Arm/Group Description:

6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 1 2
Mean (Standard Deviation)
Unit of Measure: micrograms*hour/milliliter (mcg*h/mL)
Cycle 1 - AUC(0-∞) (n=1, 1) 36900 [1]   (NA) 73800 [1]   (NA)
Cycle 2 - AUCτ (n=1, 2) 56400 [1]   (NA) 102000  (10400)
[1]
Only 1 participant included in the analysis, therefore standard deviation is not calculable.
5.Primary Outcome
Title IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohorts 1 and 2 During Cycles 3 to 5
Hide Description Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated.
Time Frame Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2)
Hide Arm/Group Description:

6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Primary Outcome
Title IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2
Hide Description [Not Specified]
Time Frame Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Cohorts 1 and 2 who received study drug and had sufficient pharmacokinetics data to calculate t1/2 for Cycles 1 and 2.
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2)
Hide Arm/Group Description:

6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 3 2
Median (Full Range)
Unit of Measure: hours
Cycle 1
158
(129 to 166)
165
(140 to 191)
Cycle 2 (n=0, 0)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Zero participants were analyzed due to the sparse pharmacokinetic sampling schedule.
7.Primary Outcome
Title IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohorts 1 and 2 During Cycles 3 to 5
Hide Description Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated.
Time Frame Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2)
Hide Arm/Group Description:

6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Primary Outcome
Title IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 1 and 2
Hide Description [Not Specified]
Time Frame Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Cohorts 1 and 2 who received study drug and had sufficient pharmacokinetics data to calculate Vss for Cycle 1. Vss is not calculated for multiple doses, therefore zero participants were analyzed for Cycle 2.
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2)
Hide Arm/Group Description:

6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 1 1
Mean (Standard Deviation)
Unit of Measure: milliliters/kilogram (mL/kg)
Cycle 1 25.0 [1]   (NA) 21.4 [1]   (NA)
Cycle 2 (n=0, 0) NA [2]   (NA) NA [2]   (NA)
[1]
Only 1 participant included in the analysis, therefore standard deviation is not calculable.
[2]
Vss is not calculated for multiple doses.
9.Primary Outcome
Title IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 3 to 5
Hide Description Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated.
Time Frame Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2)
Hide Arm/Group Description:

6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Primary Outcome
Title IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 1 and 2
Hide Description [Not Specified]
Time Frame Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Cohort 3 who received study drug and had sufficient pharmacokinetics data to calculate Cmax for Cycles 1 and 2.
Arm/Group Title IMC-1121B 10 mg/kg (Cohort 3)
Hide Arm/Group Description:

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 3 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: micrograms/milliliter (mcg/mL)
Cycle 1 493  (122)
Cycle 2 (n=2) 793  (367)
11.Primary Outcome
Title IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 3 to 5
Hide Description Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated.
Time Frame Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Arm/Group Title IMC-1121B 10 mg/kg (Cohort 3)
Hide Arm/Group Description:

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 3 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
12.Primary Outcome
Title IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohort 3 During Cycles 1 and 2
Hide Description AUC for Cycle 1 is AUC from time zero to infinity [AUC(0-∞)] and for Cycle 2 is AUC over a dosing interval (AUCτ).
Time Frame Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Cohort 3 who received study drug and had sufficient pharmacokinetics data to calculate AUC(0-∞) for Cycle 1 and AUCτ for Cycle 2.
Arm/Group Title IMC-1121B 10 mg/kg (Cohort 3)
Hide Arm/Group Description:

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 3 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: micrograms*hour/milliliter (mcg*h/mL)
Cycle 1 - AUC(0-∞) 61600  (17100)
Cycle 2 - AUCτ 103000  (26200)
13.Primary Outcome
Title IMC-1121B Pharmacokinetics - Area Under the Concentration (AUC) - Cohort 3 During Cycles 3 to 5
Hide Description Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated.
Time Frame Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Arm/Group Title IMC-1121B 10 mg/kg (Cohort 3)
Hide Arm/Group Description:

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 3 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
14.Primary Outcome
Title IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohort 3 During Cycles 1 and 2
Hide Description [Not Specified]
Time Frame Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Cohort 3 who received study drug and had sufficient pharmacokinetics data to calculate t1/2 for Cycles 1 and 2.
Arm/Group Title IMC-1121B 10 mg/kg (Cohort 3)
Hide Arm/Group Description:

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 3
Median (Full Range)
Unit of Measure: hours
Cycle 1
234
(166 to 241)
Cycle 2 (n=1)
329
(329 to 329)
15.Primary Outcome
Title IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohort 3 During Cycles 3 to 5
Hide Description Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated.
Time Frame Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Arm/Group Title IMC-1121B 10 mg/kg (Cohort 3)
Hide Arm/Group Description:

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 3 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
16.Primary Outcome
Title IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 1 and 2
Hide Description [Not Specified]
Time Frame Day 1 and Day 22 of Cycles 1 and 2 of a 6-week cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Cohort 3 who received study drug and had sufficient pharmacokinetics data to calculate Vss for Cycle 1. Vss is not calculated for multiple doses, therefore zero participants were analyzed for Cycle 2.
Arm/Group Title IMC-1121B 10 mg/kg (Cohort 3)
Hide Arm/Group Description:

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: milliliters/kilogram (mL/kg)
Cycle 1 40.7  (1.22)
Cycle 2 (n=0) NA [1]   (NA)
[1]
Vss is not calculated for multiple doses.
17.Primary Outcome
Title IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 3 to 5
Hide Description Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated.
Time Frame Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Arm/Group Title IMC-1121B 10 mg/kg
Hide Arm/Group Description:

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 3 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
18.Secondary Outcome
Title Screen for the Development of Circulating Antibodies Against IMC-1121B (Immunogenicity)
Hide Description Data presented are the number of participants with treatment emergent antibody positive.
Time Frame Baseline to study completion up to 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug.
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2) IMC-1121B 10 mg/kg (Cohort 3)
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6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 3 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

Overall Number of Participants Analyzed 3 6 6
Measure Type: Number
Unit of Measure: participants
0 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2) IMC-1121B 10 mg/kg (Cohort 3)
Hide Arm/Group Description

6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 3 weeks for 6 weeks (1 cycle).

After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met.

All-Cause Mortality
IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2) IMC-1121B 10 mg/kg (Cohort 3)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2) IMC-1121B 10 mg/kg (Cohort 3)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/3 (33.33%)      2/6 (33.33%)      2/6 (33.33%)    
Nervous system disorders       
Syncope  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Surgical and medical procedures       
Hospitalisation  1  1/3 (33.33%)  1 2/6 (33.33%)  2 1/6 (16.67%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
IMC-1121B 6 mg/kg (Cohort 1) IMC-1121B 8 mg/kg (Cohort 2) IMC-1121B 10 mg/kg (Cohort 3)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      6/6 (100.00%)      6/6 (100.00%)    
Blood and lymphatic system disorders       
Leukopenia  1  1/3 (33.33%)  1 1/6 (16.67%)  1 1/6 (16.67%)  1
Neutropenia  1  0/3 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Cardiac disorders       
Pericardial effusion  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Eye disorders       
Conjunctival haemorrhage  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Eyelid oedema  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Myodesopsia  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain upper  1  2/3 (66.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Anal haemorrhage  1  1/3 (33.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Constipation  1  1/3 (33.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Diarrhoea  1  2/3 (66.67%)  4 2/6 (33.33%)  2 1/6 (16.67%)  1
Gastritis  1  1/3 (33.33%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1
Gingival bleeding  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Gingivitis  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Nausea  1  0/3 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Stomatitis  1  1/3 (33.33%)  1 0/6 (0.00%)  0 1/6 (16.67%)  2
Vomiting  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
General disorders       
Chills  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Face oedema  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Fatigue  1  1/3 (33.33%)  1 1/6 (16.67%)  1 3/6 (50.00%)  5
Injection site pain  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Injection site rash  1  1/3 (33.33%)  5 1/6 (16.67%)  1 3/6 (50.00%)  3
Oedema peripheral  1  0/3 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Pyrexia  1  1/3 (33.33%)  1 2/6 (33.33%)  2 4/6 (66.67%)  4
Infections and infestations       
Abscess oral  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Nasopharyngitis  1  0/3 (0.00%)  0 3/6 (50.00%)  3 0/6 (0.00%)  0
Oral herpes  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Pharyngitis  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Injury, poisoning and procedural complications       
Contusion  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Fall  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Investigations       
Alanine aminotransferase increased  1  1/3 (33.33%)  1 2/6 (33.33%)  2 2/6 (33.33%)  2
Aspartate aminotransferase increased  1  2/3 (66.67%)  2 2/6 (33.33%)  2 2/6 (33.33%)  2
Blood albumin decreased  1  0/3 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0
Blood alkaline phosphatase increased  1  0/3 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Blood amylase increased  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Blood urine present  1  0/3 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Electrocardiogram T wave amplitude decreased  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Weight decreased  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Weight increased  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Metabolism and nutrition disorders       
Anorexia  1  1/3 (33.33%)  1 0/6 (0.00%)  0 2/6 (33.33%)  3
Dehydration  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Hyperkalaemia  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Hypoalbuminaemia  1  0/3 (0.00%)  0 1/6 (16.67%)  1 2/6 (33.33%)  3
Hyponatraemia  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Hypovolaemia  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Back pain  1  1/3 (33.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Musculoskeletal pain  1  1/3 (33.33%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Neck pain  1  1/3 (33.33%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Lymphangiosis carcinomatosa  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Nervous system disorders       
Dizziness  1  2/3 (66.67%)  2 1/6 (16.67%)  2 0/6 (0.00%)  0
Headache  1  1/3 (33.33%)  1 4/6 (66.67%)  5 5/6 (83.33%)  10
Peripheral sensory neuropathy  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Psychiatric disorders       
Insomnia  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Renal and urinary disorders       
Proteinuria  1  0/3 (0.00%)  0 3/6 (50.00%)  4 0/6 (0.00%)  0
Reproductive system and breast disorders       
Breast haemorrhage  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Vaginal haemorrhage  1  1/1 (100.00%)  3 0/5 (0.00%)  0 0/3 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Dysphonia  1  0/3 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2
Epistaxis  1  0/3 (0.00%)  0 2/6 (33.33%)  2 1/6 (16.67%)  1
Oropharyngeal discomfort  1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Oropharyngeal pain  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Skin and subcutaneous tissue disorders       
Acne  1  2/3 (66.67%)  3 1/6 (16.67%)  1 1/6 (16.67%)  2
Dry skin  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Haemorrhage subcutaneous  1  1/3 (33.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Palmar-plantar erythrodysaesthesia syndrome  1  2/3 (66.67%)  2 1/6 (16.67%)  1 0/6 (0.00%)  0
Pruritus  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2
Purpura  1  0/3 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Rash  1  1/3 (33.33%)  1 0/6 (0.00%)  0 2/6 (33.33%)  3
Skin exfoliation  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Urticaria  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Vascular disorders       
Hypertension  1  1/3 (33.33%)  1 3/6 (50.00%)  9 2/6 (33.33%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
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.
Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01005355     History of Changes
Other Study ID Numbers: 13898
CP12-0816 ( Other Identifier: ImClone Systems )
I4T-IE-JVBI ( Other Identifier: Eli Lilly and Company )
First Submitted: October 5, 2009
First Posted: October 30, 2009
Results First Submitted: May 16, 2014
Results First Posted: June 18, 2014
Last Update Posted: June 18, 2014