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A Comparative Study Of PF-06439535 Plus Paclitaxel-Carboplatin And Bevacizumab Plus Paclitaxel-Carboplatin Patients With Advanced Non-Squamous NSCLC

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ClinicalTrials.gov Identifier: NCT02364999
Recruitment Status : Completed
First Posted : February 18, 2015
Results First Posted : June 27, 2018
Last Update Posted : February 7, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Non-Small Cell Lung Cancer
Interventions Drug: Bevacizumab-Pfizer
Drug: Bevacizumab-EU
Drug: Paclitaxel
Drug: Carboplatin
Enrollment 719
Recruitment Details  
Pre-assignment Details A total of 719 participants were enrolled in this study, and 5 of them did not receive any therapy. One (1) additional participant received only chemotherapy, and did not receive blinded bevacizumab.
Arm/Group Title PF-06439535 Bevacizumab-EU
Hide Arm/Group Description Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin. Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Period Title: Overall Study
Started 358 361
Received Treatment 356 358
Completed 193 188
Not Completed 165 173
Reason Not Completed
Death             136             138
Lost to Follow-up             10             15
Protocol Violation             3             2
Withdrawal by Subject             14             14
Other             0             1
Randomized but did not receive treatment             2             3
Arm/Group Title PF-06439535 Bevacizumab-EU Total
Hide Arm/Group Description Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin. Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin. Total of all reporting groups
Overall Number of Baseline Participants 358 361 719
Hide Baseline Analysis Population Description
Baseline analysis population is the Intent-to-Treat (ITT) population and it included all participants who were randomized to study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 358 participants 361 participants 719 participants
61.7  (9.5) 60.9  (8.9) 61.3  (9.2)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 358 participants 361 participants 719 participants
18-44 years
19
   5.3%
17
   4.7%
36
   5.0%
45-64 years
198
  55.3%
222
  61.5%
420
  58.4%
>= 65 years
141
  39.4%
122
  33.8%
263
  36.6%
Sex/Gender, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 358 participants 361 participants 719 participants
Female
121
  33.8%
131
  36.3%
252
  35.0%
Male
237
  66.2%
230
  63.7%
467
  65.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 358 participants 361 participants 719 participants
WHITE
319
  89.1%
319
  88.4%
638
  88.7%
BLACK
3
   0.8%
1
   0.3%
4
   0.6%
ASIAN
36
  10.1%
40
  11.1%
76
  10.6%
OTHER
0
   0.0%
1
   0.3%
1
   0.1%
1.Primary Outcome
Title Objective Response Rate (ORR) by Week 19
Hide Description ORR refers to percentage of participants who achieved complete response (CR) or partial response (PR) by Week 19 of the study in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 which was subsequently confirmed by Week 25. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved PR if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits.
Time Frame 25 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population was used for analysis of ORR, and it included all participants who were randomized to study treatment.
Arm/Group Title PF-06439535 Bevacizumab-EU
Hide Arm/Group Description:
Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed 358 361
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
45.3
(40.01 to 50.57)
44.6
(39.40 to 49.89)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-06439535, Bevacizumab-EU
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments Calculated based on 2-sided Miettinen and Nurminen method without strata for risk difference for confirmed response. EU equivalence margins (95% CI in -13% to 13%).
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.6531
Confidence Interval (2-Sided) 95%
-6.6080 to 7.9082
Estimation Comments PF-06439535 vs Bevacizumab-EU
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-06439535, Bevacizumab-EU
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments Calculated based on 2-sided Miettinen and Nurminen method without strata for risk ratio for confirmed response. US equivalence margins (90% CI in 0.73 to 1.37).
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.0146
Confidence Interval (2-Sided) 90%
0.8856 to 1.1625
Estimation Comments PF-06439535 vs Bevacizumab-EU
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-06439535, Bevacizumab-EU
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments Calculated based on 2-sided Miettinen and Nurminen method without strata for risk ratio for confirmed response. Japan equivalence margins (95% CI in 0.729 to 1.371).
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.0146
Confidence Interval (2-Sided) 95%
0.8628 to 1.1933
Estimation Comments PF-06439535 vs Bevacizumab-EU
2.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events
Hide Description AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time Frame 55 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who were randomized and received at least 1 dose of study treatment.
Arm/Group Title PF-06439535 Bevacizumab-EU
Hide Arm/Group Description:
Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed 356 358
Measure Type: Count of Participants
Unit of Measure: Participants
All-causality AE
344
  96.6%
347
  96.9%
All-causality SAE
81
  22.8%
80
  22.3%
Bevacizumab-related AE
190
  53.4%
199
  55.6%
Bevacizumab-related SAE
23
   6.5%
17
   4.7%
Grade 1 all-causality AE
32
   9.0%
41
  11.5%
Grade 2 all-causality AE
141
  39.6%
134
  37.4%
Grade 3 all-causality AE
125
  35.1%
104
  29.1%
Grade 4 all-causality AE
25
   7.0%
44
  12.3%
Grade 5 all-causality AE
21
   5.9%
24
   6.7%
3.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Hide Description Laboratory evaluation included hematology (hemoglobin, white blood cells, platelets and absolute neutrophil count), blood chemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, serum or plasma creatinine, sodium, potassium, total calcium, magnesium, blood urea nitrogen or urea, and albumin ), coagulation (international normalized ratio for prothrombin time and activated partial thromboplastin time) and urinalysis (dipstick followed by a quantitative urine protein analysis for results of 2+ or greater).
Time Frame 55 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who were randomized and received at least 1 dose of study treatment, and had laboratory evaluation done.
Arm/Group Title PF-06439535 Bevacizumab-EU
Hide Arm/Group Description:
Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed 342 348
Measure Type: Count of Participants
Unit of Measure: Participants
303
  88.6%
304
  87.4%
4.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of PD or to death due to any cause in the absence of documented PD. DOR was based on the Brookmeyer and Crowley method.
Time Frame 55 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants in ITT population (all participants who were randomized to study treatment) who had a confirmed objective response achieved by Week 19.
Arm/Group Title PF-06439535 Bevacizumab-EU
Hide Arm/Group Description:
Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed 162 161
Median (95% Confidence Interval)
Unit of Measure: weeks
36.3
(31.6 to 43.6)
28.7
(27.0 to 36.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-06439535, Bevacizumab-EU
Comments [Not Specified]
Type of Statistical Test Other
Comments Hazard ratio of PF-06439535 versus Bevacizumab-EU; a hazard ratio =1 indicated no difference in progressive disease(PD)/death between 2 reporting groups; >1 indicated an increase in PD/death in PF-06439535; <1 indicated an increase in PD/death in bevacizumab-EU.
Statistical Test of Hypothesis P-Value 0.1077
Comments [Not Specified]
Method Log Rank
Comments Stratified by smoking, sex and region.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.800
Confidence Interval (2-Sided) 95%
0.608 to 1.051
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Progression Free Survival Rate at 55 Weeks
Hide Description This outcome measure refers to the possibility of being progression free at 55 weeks since start of study treatment, estimated from the Kaplan-Meier curve using the product-limit method.
Time Frame 55 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was used for analysis, and it included all participants who were randomized to study treatment.
Arm/Group Title PF-06439535 Bevacizumab-EU
Hide Arm/Group Description:
Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed 358 361
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
32.3
(26.9 to 37.8)
30.5
(25.3 to 35.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-06439535, Bevacizumab-EU
Comments [Not Specified]
Type of Statistical Test Other
Comments Hazard ratio of PF-06439535 versus Bevacizumab-EU; a hazard ratio =1 indicated no difference in progressive disease(PD)/death between 2 reporting groups; >1 indicated an increase in PD/death in PF-06439535; <1 indicated an increase in PD/death in bevacizumab-EU.
Statistical Test of Hypothesis P-Value 0.4492
Comments [Not Specified]
Method Log Rank
Comments Stratified by smoking, sex and region.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.931
Confidence Interval 95%
0.777 to 1.116
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Survival Rate at 55 Weeks
Hide Description This outcome measure refers to the possibility of being alive at 55 weeks since start of study treatment, estimated from the Kaplan-Meier curve using the product-limit method.
Time Frame 55 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was used for analysis, and it included all participants who were randomized to study treatment.
Arm/Group Title PF-06439535 Bevacizumab-EU
Hide Arm/Group Description:
Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed 358 361
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
65.8
(60.5 to 70.6)
64.1
(58.6 to 69.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-06439535, Bevacizumab-EU
Comments [Not Specified]
Type of Statistical Test Other
Comments Hazard ratio of PF-06439535 versus Bevacizumab-EU; a hazard ratio =1 indicated no difference in progressive disease(PD)/death between 2 reporting groups; >1 indicated an increase in PD/death in PF-06439535; <1 indicated an increase in PD/death in bevacizumab-EU.
Statistical Test of Hypothesis P-Value 0.4726
Comments [Not Specified]
Method Log Rank
Comments Stratified by smoking, sex and region.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.918
Confidence Interval (2-Sided) 95%
0.729 to 1.157
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Serum Concentration of Bevacizumab up to 1 Year
Hide Description [Not Specified]
Time Frame Pre-dose from Cycle 1 to Cycle 17, 2.5 hours post-dose in Cycle 1, and 1.5 hours post-dose in Cycle 5
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants in the per-protocol population (all participants who were randomized and received study treatment as planned and had no major protocol deviations) who had at least 1 drug concentration measurement after administration of study treatment.
Arm/Group Title PF-06439535 Bevacizumab-EU
Hide Arm/Group Description:
Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed 351 354
Mean (Standard Deviation)
Unit of Measure: ng/mL
Pre-dose in Cycle 1 Number Analyzed 333 participants 338 participants
68.08  (705.53) 116.4  (1032.1)
2.5 hours post-dose in Cycle 1 Number Analyzed 319 participants 326 participants
280000  (103260) 302200  (100360)
Pre-dose in Cycle 2 Number Analyzed 310 participants 326 participants
54350  (44479) 58930  (49452)
Pre-dose in Cycle 3 Number Analyzed 206 participants 211 participants
81090  (48671) 83350  (32384)
Pre-dose in Cycle 4 Number Analyzed 277 participants 299 participants
100900  (54979) 99750  (50531)
Pre-dose in Cycle 5 Number Analyzed 257 participants 271 participants
105300  (48469) 110000  (65416)
1.5 hours post-dose in Cycle 5 Number Analyzed 192 participants 201 participants
360700  (131170) 377200  (142250)
Pre-dose in Cycle 6 Number Analyzed 244 participants 268 participants
112000  (40825) 116700  (53844)
Pre-dose in Cycle 7 Number Analyzed 192 participants 214 participants
117300  (53844) 122100  (47793)
Pre-dose in Cycle 8 Number Analyzed 195 participants 208 participants
123600  (48893) 126400  (52985)
Pre-dose in Cycle 9 Number Analyzed 184 participants 193 participants
127200  (46200) 140900  (62548)
Pre-dose in Cycle 10 Number Analyzed 170 participants 179 participants
125700  (50769) 135900  (53975)
Pre-dose in Cycle 11 Number Analyzed 170 participants 169 participants
129500  (61329) 135600  (54531)
Pre-dose in Cycle 12 Number Analyzed 141 participants 138 participants
135200  (64560) 136300  (51312)
Pre-dose in Cycle 13 Number Analyzed 136 participants 121 participants
130900  (58093) 139700  (53750)
Pre-dose in Cycle 14 Number Analyzed 131 participants 117 participants
128000  (50840) 136200  (53439)
Pre-dose in Cycle 15 Number Analyzed 103 participants 104 participants
134000  (55933) 134000  (49663)
Pre-dose in Cycle 16 Number Analyzed 92 participants 95 participants
137000  (54813) 128600  (49742)
Pre-dose in Cycle 17 Number Analyzed 90 participants 92 participants
134800  (86847) 127500  (52784)
8.Secondary Outcome
Title Number of Participants With Anti-Drug Antibody (ADA)
Hide Description ADA assay was performed using a sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) method, which used biotinylated- and ruthenium-labeled PF-06439535 as reagents. Samples with ADA titer greater than or equal to (>=) 2.29 were considered positive.
Time Frame 55 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who were randomized and received at least 1 dose of study treatment.
Arm/Group Title PF-06439535 Bevacizumab-EU
Hide Arm/Group Description:
Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed 356 358
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle 1 pre-dose Number Analyzed 351 participants 353 participants
1
   0.3%
3
   0.8%
Overall (post-treatment) Number Analyzed 339 participants 350 participants
5
   1.5%
5
   1.4%
9.Secondary Outcome
Title Number of Participants With Neutralizing Antibody (NAb)
Hide Description Only samples that were confirmed positive for ADA were further tested for NAb. The NAb analysis was conducted using a single validated quasi-quantitative enzyme-linked immunosorbent assay (ELISA) that utilized PF-06439535 as a reagent. Samples with NAb titer >=1.70 were considered positive.
Time Frame 55 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who had positive ADA results at any time point.
Arm/Group Title PF-06439535 Bevacizumab-EU
Hide Arm/Group Description:
Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
Overall Number of Participants Analyzed 6 7
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle 1 pre-dose Number Analyzed 1 participants 3 participants
1
 100.0%
0
   0.0%
Overall (post-treatment) Number Analyzed 5 participants 5 participants
0
   0.0%
3
  60.0%
Time Frame 55 weeks
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
 
Arm/Group Title PF-06439535 Bevacizumab-EU Total
Hide Arm/Group Description Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin. Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant’s pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin. This reporting group include all participants who received at least 1 dose of study treatment from PF-06439535 and Bevacizumab-EU groups.
All-Cause Mortality
PF-06439535 Bevacizumab-EU Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   144/356 (40.45%)      149/358 (41.62%)      293/714 (41.04%)    
Show Serious Adverse Events Hide Serious Adverse Events
PF-06439535 Bevacizumab-EU Total
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   81/356 (22.75%)      80/358 (22.35%)      161/714 (22.55%)    
Blood and lymphatic system disorders       
Anaemia * 1  2/356 (0.56%)  4 5/358 (1.40%)  6 7/714 (0.98%)  10
Febrile neutropenia * 1  5/356 (1.40%)  7 7/358 (1.96%)  7 12/714 (1.68%)  14
Leukopenia * 1  2/356 (0.56%)  3 0/358 (0.00%)  0 2/714 (0.28%)  3
Neutropenia * 1  4/356 (1.12%)  5 6/358 (1.68%)  8 10/714 (1.40%)  13
Pancytopenia * 1  1/356 (0.28%)  2 1/358 (0.28%)  1 2/714 (0.28%)  3
Thrombocytopenia * 1  3/356 (0.84%)  5 3/358 (0.84%)  3 6/714 (0.84%)  8
Cardiac disorders       
Acute coronary syndrome * 1  1/356 (0.28%)  1 1/358 (0.28%)  1 2/714 (0.28%)  2
Acute myocardial infarction * 1  1/356 (0.28%)  1 1/358 (0.28%)  1 2/714 (0.28%)  2
Angina unstable * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Cardiac arrest * 1  1/356 (0.28%)  1 1/358 (0.28%)  1 2/714 (0.28%)  2
Cardiac failure * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Cardio-respiratory arrest * 1  0/356 (0.00%)  0 2/358 (0.56%)  2 2/714 (0.28%)  2
Cardiovascular insufficiency * 1  1/356 (0.28%)  1 1/358 (0.28%)  1 2/714 (0.28%)  2
Myocardial infarction * 1  1/356 (0.28%)  1 1/358 (0.28%)  1 2/714 (0.28%)  2
Right ventricular failure * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Gastrointestinal disorders       
Abdominal pain * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Colitis * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Colitis ischaemic * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Constipation * 1  0/356 (0.00%)  0 2/358 (0.56%)  2 2/714 (0.28%)  2
Diarrhoea * 1  2/356 (0.56%)  3 2/358 (0.56%)  3 4/714 (0.56%)  6
Enterocolitis * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Faecaloma * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Gastritis * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Haemorrhoidal haemorrhage * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Ileus * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Intestinal obstruction * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Nausea * 1  0/356 (0.00%)  0 2/358 (0.56%)  2 2/714 (0.28%)  2
Neutropenic colitis * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Peptic ulcer * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Rectal haemorrhage * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Small intestinal perforation * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Subileus * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Vomiting * 1  1/356 (0.28%)  1 1/358 (0.28%)  1 2/714 (0.28%)  2
General disorders       
Asthenia * 1  4/356 (1.12%)  5 1/358 (0.28%)  1 5/714 (0.70%)  6
Chest pain * 1  1/356 (0.28%)  1 1/358 (0.28%)  1 2/714 (0.28%)  2
Death * 1  2/356 (0.56%)  2 3/358 (0.84%)  3 5/714 (0.70%)  5
Disease progression * 1  4/356 (1.12%)  4 5/358 (1.40%)  5 9/714 (1.26%)  9
General physical health deterioration * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Pain * 1  2/356 (0.56%)  2 1/358 (0.28%)  1 3/714 (0.42%)  3
Hepatobiliary disorders       
Cholangitis acute * 1  2/356 (0.56%)  2 0/358 (0.00%)  0 2/714 (0.28%)  2
Cholelithiasis * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Immune system disorders       
Anaphylactic reaction * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Infections and infestations       
Anal infection * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Appendicitis perforated * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Bacteraemia * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Disseminated tuberculosis * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Enterocolitis infectious * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Febrile infection * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Gastroenteritis * 1  4/356 (1.12%)  4 0/358 (0.00%)  0 4/714 (0.56%)  4
Infection * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Infectious pleural effusion * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Lower respiratory tract infection * 1  1/356 (0.28%)  1 2/358 (0.56%)  2 3/714 (0.42%)  3
Lung abscess * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Lung infection * 1  1/356 (0.28%)  1 1/358 (0.28%)  1 2/714 (0.28%)  2
Oral fungal infection * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Pleural infection * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Pneumonia * 1  8/356 (2.25%)  11 6/358 (1.68%)  6 14/714 (1.96%)  17
Respiratory tract infection * 1  2/356 (0.56%)  2 0/358 (0.00%)  0 2/714 (0.28%)  2
Sepsis * 1  0/356 (0.00%)  0 2/358 (0.56%)  2 2/714 (0.28%)  2
Septic shock * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Sinusitis * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Soft tissue infection * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Urinary tract infection * 1  1/356 (0.28%)  1 2/358 (0.56%)  3 3/714 (0.42%)  4
Injury, poisoning and procedural complications       
Femur fracture * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Fracture * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Infusion related reaction * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Subarachnoid haemorrhage * 1  0/356 (0.00%)  0 1/358 (0.28%)  2 1/714 (0.14%)  2
Investigations       
Alanine aminotransferase increased * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Blood bilirubin increased * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Neutrophil count decreased * 1  1/356 (0.28%)  1 1/358 (0.28%)  1 2/714 (0.28%)  2
Metabolism and nutrition disorders       
Decreased appetite * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Dehydration * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Hypercalcaemia * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Hyperkalaemia * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Hyponatraemia * 1  4/356 (1.12%)  5 0/358 (0.00%)  0 4/714 (0.56%)  5
Musculoskeletal and connective tissue disorders       
Bone pain * 1  0/356 (0.00%)  0 2/358 (0.56%)  2 2/714 (0.28%)  2
Myalgia * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Bone cancer metastatic * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Neoplasm progression * 1  2/356 (0.56%)  3 2/358 (0.56%)  2 4/714 (0.56%)  5
Tumour necrosis * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Nervous system disorders       
Cerebral haemorrhage * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Cerebral ischaemia * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Dizziness * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Haemorrhagic stroke * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Headache * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Ischaemic stroke * 1  0/356 (0.00%)  0 3/358 (0.84%)  4 3/714 (0.42%)  4
Mononeuropathy * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Paraesthesia * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Renal and urinary disorders       
Proteinuria * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Renal cyst * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Urinary retention * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Chronic obstructive pulmonary disease * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Cough * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Dyspnoea * 1  2/356 (0.56%)  2 2/358 (0.56%)  2 4/714 (0.56%)  4
Epistaxis * 1  2/356 (0.56%)  2 1/358 (0.28%)  2 3/714 (0.42%)  4
Haemoptysis * 1  2/356 (0.56%)  2 2/358 (0.56%)  3 4/714 (0.56%)  5
Pneumonitis * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Pneumothorax * 1  2/356 (0.56%)  2 1/358 (0.28%)  1 3/714 (0.42%)  3
Pulmonary embolism * 1  7/356 (1.97%)  7 2/358 (0.56%)  2 9/714 (1.26%)  9
Pulmonary haemorrhage * 1  3/356 (0.84%)  3 3/358 (0.84%)  3 6/714 (0.84%)  6
Pulmonary oedema * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Respiratory failure * 1  1/356 (0.28%)  2 0/358 (0.00%)  0 1/714 (0.14%)  2
Vascular disorders       
Brachiocephalic vein thrombosis * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Embolism arterial * 1  1/356 (0.28%)  1 1/358 (0.28%)  1 2/714 (0.28%)  2
Haemorrhage * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Hypertensive crisis * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Ischaemia * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
Shock haemorrhagic * 1  0/356 (0.00%)  0 1/358 (0.28%)  1 1/714 (0.14%)  1
Subgaleal haematoma * 1  1/356 (0.28%)  1 0/358 (0.00%)  0 1/714 (0.14%)  1
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PF-06439535 Bevacizumab-EU Total
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   328/356 (92.13%)      333/358 (93.02%)      661/714 (92.58%)    
Blood and lymphatic system disorders       
Leukopenia * 1  26/356 (7.30%)  44 30/358 (8.38%)  56 56/714 (7.84%)  100
Neutropenia * 1  59/356 (16.57%)  130 66/358 (18.44%)  144 125/714 (17.51%)  274
Thrombocytopenia * 1  55/356 (15.45%)  122 66/358 (18.44%)  125 121/714 (16.95%)  247
Anaemia * 1  102/356 (28.65%)  196 106/358 (29.61%)  200 208/714 (29.13%)  396
Gastrointestinal disorders       
Constipation * 1  39/356 (10.96%)  45 27/358 (7.54%)  36 66/714 (9.24%)  81
Diarrhoea * 1  46/356 (12.92%)  59 48/358 (13.41%)  66 94/714 (13.17%)  125
Nausea * 1  71/356 (19.94%)  111 69/358 (19.27%)  112 140/714 (19.61%)  223
Vomiting * 1  41/356 (11.52%)  52 33/358 (9.22%)  42 74/714 (10.36%)  94
General disorders       
Asthenia * 1  46/356 (12.92%)  78 43/358 (12.01%)  65 89/714 (12.46%)  143
Fatigue * 1  73/356 (20.51%)  110 71/358 (19.83%)  87 144/714 (20.17%)  197
Pyrexia * 1  24/356 (6.74%)  31 23/358 (6.42%)  41 47/714 (6.58%)  72
Injury, poisoning and procedural complications       
Infusion related reaction * 1  19/356 (5.34%)  26 22/358 (6.15%)  26 41/714 (5.74%)  52
Investigations       
Alanine aminotransferase increased * 1  49/356 (13.76%)  95 39/358 (10.89%)  53 88/714 (12.32%)  148
Aspartate aminotransferase increased * 1  44/356 (12.36%)  94 37/358 (10.34%)  59 81/714 (11.34%)  153
Blood alkaline phosphatase increased * 1  29/356 (8.15%)  46 32/358 (8.94%)  48 61/714 (8.54%)  94
Blood creatinine increased * 1  16/356 (4.49%)  28 21/358 (5.87%)  33 37/714 (5.18%)  61
Platelet count decreased * 1  23/356 (6.46%)  31 19/358 (5.31%)  38 42/714 (5.88%)  69
Weight decreased * 1  36/356 (10.11%)  43 29/358 (8.10%)  40 65/714 (9.10%)  83
Metabolism and nutrition disorders       
Decreased appetite * 1  48/356 (13.48%)  76 46/358 (12.85%)  65 94/714 (13.17%)  141
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  40/356 (11.24%)  82 43/358 (12.01%)  71 83/714 (11.62%)  153
Bone pain * 1  25/356 (7.02%)  58 23/358 (6.42%)  47 48/714 (6.72%)  105
Myalgia * 1  54/356 (15.17%)  131 49/358 (13.69%)  109 103/714 (14.43%)  240
Pain in extremity * 1  16/356 (4.49%)  23 23/358 (6.42%)  29 39/714 (5.46%)  52
Nervous system disorders       
Headache * 1  30/356 (8.43%)  35 37/358 (10.34%)  45 67/714 (9.38%)  80
Neuropathy peripheral * 1  53/356 (14.89%)  67 65/358 (18.16%)  86 118/714 (16.53%)  153
Paraesthesia * 1  40/356 (11.24%)  64 31/358 (8.66%)  36 71/714 (9.94%)  100
Peripheral sensory neuropathy * 1  34/356 (9.55%)  45 46/358 (12.85%)  70 80/714 (11.20%)  115
Polyneuropathy * 1  23/356 (6.46%)  34 19/358 (5.31%)  22 42/714 (5.88%)  56
Renal and urinary disorders       
Proteinuria * 1  28/356 (7.87%)  50 34/358 (9.50%)  76 62/714 (8.68%)  126
Respiratory, thoracic and mediastinal disorders       
Cough * 1  41/356 (11.52%)  53 47/358 (13.13%)  58 88/714 (12.32%)  111
Dyspnoea * 1  32/356 (8.99%)  38 35/358 (9.78%)  41 67/714 (9.38%)  79
Epistaxis * 1  40/356 (11.24%)  51 32/358 (8.94%)  48 72/714 (10.08%)  99
Skin and subcutaneous tissue disorders       
Alopecia * 1  166/356 (46.63%)  216 165/358 (46.09%)  232 331/714 (46.36%)  448
Rash * 1  9/356 (2.53%)  10 21/358 (5.87%)  29 30/714 (4.20%)  39
Vascular disorders       
Hypertension * 1  60/356 (16.85%)  83 62/358 (17.32%)  110 122/714 (17.09%)  193
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
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
Layout table for Results Point of Contact information
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: NCT02364999     History of Changes
Other Study ID Numbers: B7391003
2014-003878-16 ( EudraCT Number )
B7391003 ( Other Identifier: Alias Study Number )
First Submitted: February 10, 2015
First Posted: February 18, 2015
Results First Submitted: May 7, 2018
Results First Posted: June 27, 2018
Last Update Posted: February 7, 2019