Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pertuzumab in Platinum-Resistant Low Human Epidermal Growth Factor Receptor 3 (HER3) Messenger Ribonucleic Acid (mRNA) Epithelial Ovarian Cancer (PENELOPE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01684878
Recruitment Status : Completed
First Posted : September 13, 2012
Results First Posted : November 23, 2016
Last Update Posted : May 23, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Ovarian Cancer
Interventions Drug: Gemcitabine (Chemotherapy)
Drug: Paclitaxel (Chemotherapy)
Drug: Pertuzumab
Drug: Placebo
Drug: Topotecan (Chemotherapy)
Enrollment 208
Recruitment Details  
Pre-assignment Details A total of 208 participants were entered into the study, 52 participants in Part 1, and 156 participants in Part 2 of the study. Of these, 203 received treatment with pertuzumab or pertuzumab-placebo (50 participants in Part 1 and 153 participants in Part 2).
Arm/Group Title Part 1: Pertuzumab + Topotecan Part 1: Pertuzumab + Paclitaxel Part 2: Pertuzumab+Chemotherapy Part 2: Placebo+Chemotherapy
Hide Arm/Group Description Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion. Participants received pertuzumab-matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Period Title: Part 1: Safety Run in Phase
Started 22 28 0 0
Completed 6 5 0 0
Not Completed 16 23 0 0
Reason Not Completed
Participants withdrawn consent             1             1             0             0
Death             15             20             0             0
Lost to Follow-up             0             2             0             0
Period Title: Part 2: Randomized Phase
Started 0 0 78 78
Participants Randomized But Not Treated 0 0 1 2
Participants Mis-randomized 0 0 2 0
Completed 0 0 0 0
Not Completed 0 0 78 78
Reason Not Completed
Participant withdrew consent             0             0             1             2
Lost to Follow-up             0             0             2             0
Death             0             0             62             68
Alive at data-cut             0             0             13             7
Participant noncompliance             0             0             0             1
Arm/Group Title Part 1: Pertuzumab + Topotecan Part 1: Pertuzumab + Paclitaxel Part 2: Pertuzumab+Chemotherapy Part 2: Placebo+Chemotherapy Total
Hide Arm/Group Description Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion. Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion. Total of all reporting groups
Overall Number of Baseline Participants 22 28 78 78 206
Hide Baseline Analysis Population Description
Part 1: all participants enrolled and treated in Part 1 of the study (‘as treated’ analysis) and Part 2: intent-to-treat (ITT) population was defined as all randomized participants in the group to which they were randomly assigned (‘as randomized’ analysis).
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 22 participants 28 participants 78 participants 78 participants 206 participants
Less than or equal to (≤)65 years 15 17 40 44 116
Greater than (>)65 years 7 11 38 34 90
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 28 participants 78 participants 78 participants 206 participants
Female
22
 100.0%
28
 100.0%
78
 100.0%
78
 100.0%
206
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Part 1: Percentage of Participants With Adverse Events (AEs)
Hide Description An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated population included all participants enrolled and treated in Part 1 of the study (‘as treated’ analysis) and who had received at least 1 dose of pertuzumab or chemotherapy.
Arm/Group Title Part 1: Pertuzumab + Topotecan Part 1: Pertuzumab + Paclitaxel
Hide Arm/Group Description:
Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Overall Number of Participants Analyzed 22 28
Measure Type: Number
Unit of Measure: percentage of participants
95.5 100.0
2.Primary Outcome
Title Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO)
Hide Description PFS (IRC-Assessed) was defined as the time from randomization into Part 2 of the trial until progressive disease (PD), MBO or death from any cause, whichever occurred first per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
Time Frame Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population was defined as all randomized participants in the group to which they were randomly assigned (‘as randomized’ analysis).
Arm/Group Title Part 2: Pertuzumab+Chemotherapy Part 2: Placebo+Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Overall Number of Participants Analyzed 78 78
Median (95% Confidence Interval)
Unit of Measure: months
4.27
(3.65 to 6.11)
2.74
(2.14 to 4.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pertuzumab+Chemotherapy, Part 2: Placebo+Chemotherapy
Comments The stratified time-to-event analysis included the treatment group variable plus the following stratification factors: selected chemotherapy cohort (gemcitabine versus topotecan vs paclitaxel), previous anti-angiogenic therapy (yes versus no), and progression-free interval (PFI) since platinum therapy (< 3 months versus 3-6 months). A hazard ratio < 1 favored the pertuzumab + chemotherapy treatment arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4983
Comments [Not Specified]
Method 2 sided log-rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (stratified)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.62 to 1.27
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Part 1- Objective Response Rate (ORR)
Hide Description ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame Approximately 28 months (assessed at baseline and every 9 weeks from randomization until disease progression)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated participants with measurable disease at baseline.
Arm/Group Title Part 1: Pertuzumab + Topotecan Part 1: Pertuzumab + Paclitaxel
Hide Arm/Group Description:
Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Overall Number of Participants Analyzed 14 24
Measure Type: Number
Unit of Measure: percentage of participants
14.3 25.0
4.Secondary Outcome
Title Part 2- Objective Response Rate (ORR)
Hide Description ORR was defined as the number of participants with BOR of CR or PR recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with measurable disease at baseline.
Arm/Group Title Part 2: Pertuzumab+Chemotherapy Part 2: Placebo+Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Overall Number of Participants Analyzed 61 69
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
14.8
(7.0 to 26.2)
8.7
(3.3 to 18.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pertuzumab+Chemotherapy, Part 2: Placebo+Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4102
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rate
Estimated Value 6.06
Confidence Interval (2-Sided) 95%
6.0 to 18.3
Estimation Comments Approximate 95% CI for difference of 2 rates using Hauck-Anderson method.
5.Secondary Outcome
Title Part 1: PFS Assessed by the Investigator
Hide Description PFS as assessed by Investigator was defined as the time from first dose of pertuzumab or chemotherapy in Part 1 of the trial, until disease progression according to RECIST version 1.1, symptomatic deterioration or death from any cause, whichever occurs first. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants were censored at the last tumor assessment. Participants who have no tumor assessments after baseline and who were still alive will be censored at 1 day.
Time Frame Approximately 28 months (assessed at screening and every 9 weeks from randomization until disease progression)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated population included all participants enrolled and treated in Part 1 of the study (‘as treated’ analysis) and who had received at least 1 dose of pertuzumab or chemotherapy.
Arm/Group Title Part 1: Pertuzumab + Topotecan Part 1: Pertuzumab + Paclitaxel
Hide Arm/Group Description:
Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.
Overall Number of Participants Analyzed 22 28
Median (95% Confidence Interval)
Unit of Measure: months
4.07
(1.94 to 6.08)
4.24
(3.45 to 6.01)
6.Secondary Outcome
Title Part 2: Progression-free Survival (PFS) Assessed by the Investigator
Hide Description PFS (Investigator-assessed) is defined as the time from randomization, until disease progression according to RECIST v1.1 including death or MBO, whichever occurs first. Censoring is based on the last tumor assessment. If no tumor assessment post baseline, then censoring is at day 1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
Time Frame Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all randomized participants in the group to which they were randomly assigned (‘as randomized’ analysis)
Arm/Group Title Part 2: Pertuzumab+Chemotherapy Part 2: Placebo+Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Overall Number of Participants Analyzed 78 78
Median (95% Confidence Interval)
Unit of Measure: months
4.22
(3.25 to 5.22)
3.94
(2.63 to 4.30)
7.Secondary Outcome
Title Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score
Hide Description EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scores, a higher score represents a more severe level of symptoms. For the global health status scores, a higher score represents a better quality of life.
Time Frame Baseline (assessed at baseline and every 9 weeks from randomization until disease progression)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants in the group to which they were randomly assigned (‘as randomized’ analysis).
Arm/Group Title Part 2: Pertuzumab+Chemotherapy Part 2: Placebo+Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Overall Number of Participants Analyzed 78 78
Mean (Standard Deviation)
Unit of Measure: units on a scale
Functional Scales: Physical (n=71, 74) 71.1  (22.77) 74.9  (20.85)
Functional Scales: Role (n=70, 73) 68.6  (33.16) 69.4  (32.40)
Functional Scales: Emotional (n=71, 73) 59.5  (24.03) 65.9  (23.42)
Functional Scales: Cognitive (n=71, 73) 81.2  (25.34) 84.9  (20.25)
Functional Scales: Social (n=71, 73) 70.7  (30.01) 68.3  (29.81)
Symptomatic Scales: Fatigue (n=71, 74) 41.2  (28.75) 38.4  (27.77)
Symptomatic Scales: Nausea and vomiting (n=72, 74) 10.4  (15.68) 12.4  (20.47)
Symptomatic Scales: Pain (n=72, 74) 35.2  (31.34) 31.1  (29.24)
Symptomatic Scales: Dyspnoea (n=68, 73) 22.5  (28.47) 21.5  (27.98)
Symptomatic Scales: Insomnia (n=69, 74) 35.3  (31.25) 31.5  (31.16)
Symptomatic Scales: Appetite loss (n=71, 73) 24.9  (30.19) 21.0  (26.36)
Symptomatic Scales: Constipation (n=69, 72) 25.6  (32.41) 26.4  (32.59)
Symptomatic Scales: Diarrhoea (n=69, 72) 14.5  (26.49) 14.4  (22.26)
Symptomatic Scales:Financial difficulties(n=70,72 17.6  (28.78) 13.4  (22.83)
Global health status / QoL scale (n=71, 72) 54.1  (24.99) 61.1  (22.29)
8.Secondary Outcome
Title Part 2: Percentage of Participants With Adverse Events (AEs)
Hide Description An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who had received at least 1 dose of pertuzumab, pertuzumab-placebo, or chemotherapy.
Arm/Group Title Part 2: Pertuzumab+Chemotherapy Part 2: Placebo+Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Overall Number of Participants Analyzed 77 76
Measure Type: Number
Unit of Measure: percentage of participants
98.7 100
9.Secondary Outcome
Title Part 2: Overall Survival
Hide Description Overall survival was defined as the time from randomization into Part 2 of the trial until death from any cause
Time Frame Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all randomized participants in the group to which they were randomly assigned (‘as randomized’ analysis)
Arm/Group Title Part 2: Pertuzumab+Chemotherapy Part 2: Placebo+Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
Overall Number of Participants Analyzed 78 78
Median (95% Confidence Interval)
Unit of Measure: months
10.18
(6.67 to 15.24)
8.36
(6.14 to 11.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pertuzumab+Chemotherapy, Part 2: Placebo+Chemotherapy
Comments The stratified time-to-event analysis included the treatment group variable plus the following stratification factors: selected chemotherapy cohort (gemcitabine versus topotecan versus paclitaxel), previous angiogenic therapy (yes versus no) and PFI since platinum therapy (<3 months versus 3-6 months).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5960
Comments [Not Specified]
Method 2 sided log-rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard ratio (stratified)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.61 to 1.32
Estimation Comments A hazard ratio < 1 favored the Pertuzumab + Chemotherapy treatment group
Time Frame Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part 1: Pertuzumab + Topotecan Part 1: Pertuzumab + Paclitaxel Part 2: Pertuzumab+Chemotherapy Part 2: Placebo+Chemotherapy
Hide Arm/Group Description Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion. Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
All-Cause Mortality
Part 1: Pertuzumab + Topotecan Part 1: Pertuzumab + Paclitaxel Part 2: Pertuzumab+Chemotherapy Part 2: Placebo+Chemotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Part 1: Pertuzumab + Topotecan Part 1: Pertuzumab + Paclitaxel Part 2: Pertuzumab+Chemotherapy Part 2: Placebo+Chemotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/22 (40.91%)   11/28 (39.29%)   29/77 (37.66%)   33/76 (43.42%) 
Blood and lymphatic system disorders         
Anaemia  1  0/22 (0.00%)  2/28 (7.14%)  1/77 (1.30%)  2/76 (2.63%) 
Neutropenia  1  2/22 (9.09%)  0/28 (0.00%)  0/77 (0.00%)  0/76 (0.00%) 
Febrile Neutropenia  1  1/22 (4.55%)  0/28 (0.00%)  2/77 (2.60%)  1/76 (1.32%) 
Pancytopenia  1  1/22 (4.55%)  0/28 (0.00%)  2/77 (2.60%)  1/76 (1.32%) 
Bone Marrow Failure  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Leukopenia  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Thrombocytopenia  1  0/22 (0.00%)  0/28 (0.00%)  3/77 (3.90%)  1/76 (1.32%) 
Cardiac disorders         
Acute Coronary Syndrome  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Acute Myocardial Infarction  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Angina Pectoris  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Cardiac Failure  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Gastrointestinal disorders         
Intestinal Obstruction  1  0/22 (0.00%)  2/28 (7.14%)  0/77 (0.00%)  4/76 (5.26%) 
Abdominal Pain  1  1/22 (4.55%)  0/28 (0.00%)  2/77 (2.60%)  2/76 (2.63%) 
Diarrhoea  1  1/22 (4.55%)  0/28 (0.00%)  4/77 (5.19%)  0/76 (0.00%) 
Nausea  1  1/22 (4.55%)  0/28 (0.00%)  1/77 (1.30%)  1/76 (1.32%) 
Subileus  1  1/22 (4.55%)  0/28 (0.00%)  3/77 (3.90%)  1/76 (1.32%) 
Vomiting  1  1/22 (4.55%)  0/28 (0.00%)  3/77 (3.90%)  2/76 (2.63%) 
Abdominal Pain Lower  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Abdominal Pain Upper  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Anal Fissure  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Ascites  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  1/76 (1.32%) 
Constipation  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Duodenal Fistula  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Ileus  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  2/76 (2.63%) 
General disorders         
Pyrexia  1  0/22 (0.00%)  2/28 (7.14%)  1/77 (1.30%)  2/76 (2.63%) 
Death  1  0/22 (0.00%)  1/28 (3.57%)  2/77 (2.60%)  0/76 (0.00%) 
Asthenia  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
General Physical Health Deterioration  1  0/22 (0.00%)  0/28 (0.00%)  2/77 (2.60%)  3/76 (3.95%) 
Performance Status Decreased  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Not yet coded  1 [1]  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Infections and infestations         
Abdominal Infection  1  0/22 (0.00%)  1/28 (3.57%)  1/77 (1.30%)  0/76 (0.00%) 
Device Related Infection  1  0/22 (0.00%)  1/28 (3.57%)  0/77 (0.00%)  0/76 (0.00%) 
Peritonitis  1  1/22 (4.55%)  0/28 (0.00%)  0/77 (0.00%)  0/76 (0.00%) 
Pyelonephritis  1  0/22 (0.00%)  1/28 (3.57%)  0/77 (0.00%)  0/76 (0.00%) 
Urinary Tract Infection  1  0/22 (0.00%)  1/28 (3.57%)  1/77 (1.30%)  1/76 (1.32%) 
Anal Abscess  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Encephalitis  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Infection  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  1/76 (1.32%) 
Infective Myositis  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Kidney Infection  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Meningitis Pneumococcal  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Respiratory Tract Infection  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Sepsis  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  1/76 (1.32%) 
Staphylococcal Infection  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Injury, poisoning and procedural complications         
Contrast Media Reaction  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Femoral Neck Fracture  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Humerus Fracture  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Investigations         
Neutrophil Count Decreased  1  0/22 (0.00%)  0/28 (0.00%)  2/77 (2.60%)  1/76 (1.32%) 
Platelet Count Decreased  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Weight Decreased  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Metabolism and nutrition disorders         
Decreased Appetite  1  1/22 (4.55%)  0/28 (0.00%)  0/77 (0.00%)  0/76 (0.00%) 
Hypokalaemia  1  1/22 (4.55%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Dehydration  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Ovarian Cancer  1  0/22 (0.00%)  0/28 (0.00%)  3/77 (3.90%)  2/76 (2.63%) 
Nervous system disorders         
Cerebral Ischaemia  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Hydrocephalus  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Ischaemic Stroke  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Renal and urinary disorders         
Haematuria  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Urinary Tract Disorder  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Urinary Tract Obstruction  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Reproductive system and breast disorders         
Vaginal Fistula  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  0/22 (0.00%)  1/28 (3.57%)  2/77 (2.60%)  1/76 (1.32%) 
Pleural Effusion  1  1/22 (4.55%)  0/28 (0.00%)  0/77 (0.00%)  2/76 (2.63%) 
Skin and subcutaneous tissue disorders         
Rash  1  0/22 (0.00%)  1/28 (3.57%)  0/77 (0.00%)  0/76 (0.00%) 
Eczema Asteatotic  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Vascular disorders         
Deep Vein Thrombosis  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  2/76 (2.63%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.1)
[1]
This adverse event was not coded at the time of the primary analysis. The preferred term will be reported when available at the final analysis.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Pertuzumab + Topotecan Part 1: Pertuzumab + Paclitaxel Part 2: Pertuzumab+Chemotherapy Part 2: Placebo+Chemotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   21/22 (95.45%)   27/28 (96.43%)   72/77 (93.51%)   75/76 (98.68%) 
Blood and lymphatic system disorders         
Anaemia  1  15/22 (68.18%)  10/28 (35.71%)  28/77 (36.36%)  32/76 (42.11%) 
Neutropenia  1  5/22 (22.73%)  3/28 (10.71%)  23/77 (29.87%)  21/76 (27.63%) 
Thrombocytopenia  1  3/22 (13.64%)  0/28 (0.00%)  3/77 (3.90%)  5/76 (6.58%) 
Leukopenia  1  1/22 (4.55%)  2/28 (7.14%)  4/77 (5.19%)  9/76 (11.84%) 
Thrombocytosis  1  3/22 (13.64%)  0/28 (0.00%)  0/77 (0.00%)  0/76 (0.00%) 
Febrile Neutropenia  1  2/22 (9.09%)  0/28 (0.00%)  0/77 (0.00%)  0/76 (0.00%) 
Ear and labyrinth disorders         
Vertigo  1  0/22 (0.00%)  2/28 (7.14%)  0/77 (0.00%)  0/76 (0.00%) 
Eye disorders         
Vision Blurred  1  0/22 (0.00%)  2/28 (7.14%)  0/77 (0.00%)  0/76 (0.00%) 
Gastrointestinal disorders         
Diarrhoea  1  14/22 (63.64%)  22/28 (78.57%)  50/77 (64.94%)  23/76 (30.26%) 
Nausea  1  11/22 (50.00%)  10/28 (35.71%)  31/77 (40.26%)  34/76 (44.74%) 
Vomiting  1  13/22 (59.09%)  5/28 (17.86%)  19/77 (24.68%)  23/76 (30.26%) 
Abdominal Pain  1  6/22 (27.27%)  4/28 (14.29%)  16/77 (20.78%)  21/76 (27.63%) 
Constipation  1  5/22 (22.73%)  5/28 (17.86%)  12/77 (15.58%)  22/76 (28.95%) 
Stomatitis  1  2/22 (9.09%)  5/28 (17.86%)  9/77 (11.69%)  5/76 (6.58%) 
Abdominal Pain Upper  1  3/22 (13.64%)  1/28 (3.57%)  6/77 (7.79%)  9/76 (11.84%) 
Dyspepsia  1  1/22 (4.55%)  3/28 (10.71%)  4/77 (5.19%)  3/76 (3.95%) 
Dry Mouth  1  0/22 (0.00%)  2/28 (7.14%)  2/77 (2.60%)  7/76 (9.21%) 
Rectal Haemorrhage  1  2/22 (9.09%)  0/28 (0.00%)  0/77 (0.00%)  0/76 (0.00%) 
Abdominal Distension  1  0/22 (0.00%)  0/28 (0.00%)  4/77 (5.19%)  5/76 (6.58%) 
Gastrooesophageal Reflux Disease  1  0/22 (0.00%)  0/28 (0.00%)  4/77 (5.19%)  1/76 (1.32%) 
General disorders         
Asthenia  1  14/22 (63.64%)  8/28 (28.57%)  32/77 (41.56%)  24/76 (31.58%) 
Fatigue  1  5/22 (22.73%)  10/28 (35.71%)  21/77 (27.27%)  24/76 (31.58%) 
Pyrexia  1  5/22 (22.73%)  5/28 (17.86%)  9/77 (11.69%)  12/76 (15.79%) 
Mucosal Inflammation  1  7/22 (31.82%)  2/28 (7.14%)  11/77 (14.29%)  6/76 (7.89%) 
Oedema Peripheral  1  5/22 (22.73%)  2/28 (7.14%)  12/77 (15.58%)  9/76 (11.84%) 
Influenza Like Illness  1  3/22 (13.64%)  0/28 (0.00%)  4/77 (5.19%)  1/76 (1.32%) 
Malaise  1  0/22 (0.00%)  2/28 (7.14%)  0/77 (0.00%)  0/76 (0.00%) 
Oedema  1  0/22 (0.00%)  2/28 (7.14%)  0/77 (0.00%)  0/76 (0.00%) 
Infections and infestations         
Nasopharyngitis  1  2/22 (9.09%)  2/28 (7.14%)  10/77 (12.99%)  6/76 (7.89%) 
Urinary Tract Infection  1  3/22 (13.64%)  1/28 (3.57%)  7/77 (9.09%)  4/76 (5.26%) 
Nail Infection  1  2/22 (9.09%)  0/28 (0.00%)  0/77 (0.00%)  0/76 (0.00%) 
Upper Respiratory Tract Infection  1  0/22 (0.00%)  0/28 (0.00%)  4/77 (5.19%)  2/76 (2.63%) 
Rhinitis  1  0/22 (0.00%)  0/28 (0.00%)  4/77 (5.19%)  1/76 (1.32%) 
Investigations         
Weight Decreased  1  2/22 (9.09%)  2/28 (7.14%)  2/77 (2.60%)  4/76 (5.26%) 
Ejection Fraction Decreased  1  0/22 (0.00%)  2/28 (7.14%)  0/77 (0.00%)  0/76 (0.00%) 
Lymphocyte Count Decreased  1  0/22 (0.00%)  2/28 (7.14%)  0/77 (0.00%)  0/76 (0.00%) 
Alanine Aminotransferase Increased  1  0/22 (0.00%)  0/28 (0.00%)  5/77 (6.49%)  6/76 (7.89%) 
White Blood Cell Count Decreased  1  0/22 (0.00%)  0/28 (0.00%)  6/77 (7.79%)  5/76 (6.58%) 
Gamma-Glutamyltransferase Increased  1  0/22 (0.00%)  0/28 (0.00%)  3/77 (3.90%)  7/76 (9.21%) 
Neutrophil Count Decreased  1  0/22 (0.00%)  0/28 (0.00%)  7/77 (9.09%)  2/76 (2.63%) 
Aspartate Aminotransferase Increased  1  0/22 (0.00%)  0/28 (0.00%)  3/77 (3.90%)  5/76 (6.58%) 
Blood Alkaline Phosphatase Increased  1  0/22 (0.00%)  0/28 (0.00%)  3/77 (3.90%)  5/76 (6.58%) 
Platelet Count Decreased  1  0/22 (0.00%)  0/28 (0.00%)  6/77 (7.79%)  2/76 (2.63%) 
Blood Creatinine Increased  1  0/22 (0.00%)  0/28 (0.00%)  1/77 (1.30%)  4/76 (5.26%) 
Metabolism and nutrition disorders         
Decreased Appetite  1  8/22 (36.36%)  5/28 (17.86%)  13/77 (16.88%)  17/76 (22.37%) 
Hypomagnesaemia  1  3/22 (13.64%)  4/28 (14.29%)  7/77 (9.09%)  7/76 (9.21%) 
Hypokalaemia  1  1/22 (4.55%)  2/28 (7.14%)  9/77 (11.69%)  5/76 (6.58%) 
Hypoalbuminaemia  1  0/22 (0.00%)  2/28 (7.14%)  0/77 (0.00%)  0/76 (0.00%) 
Hyponatraemia  1  0/22 (0.00%)  2/28 (7.14%)  0/77 (0.00%)  0/76 (0.00%) 
Hypocalcaemia  1  0/22 (0.00%)  0/28 (0.00%)  4/77 (5.19%)  0/76 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back Pain  1  1/22 (4.55%)  6/28 (21.43%)  8/77 (10.39%)  9/76 (11.84%) 
Myalgia  1  1/22 (4.55%)  4/28 (14.29%)  0/77 (0.00%)  0/76 (0.00%) 
Arthralgia  1  0/22 (0.00%)  4/28 (14.29%)  4/77 (5.19%)  5/76 (6.58%) 
Muscle Spasms  1  0/22 (0.00%)  0/28 (0.00%)  6/77 (7.79%)  3/76 (3.95%) 
Musculoskeletal Pain  1  0/22 (0.00%)  0/28 (0.00%)  2/77 (2.60%)  4/76 (5.26%) 
Pain In Extremity  1  0/22 (0.00%)  0/28 (0.00%)  4/77 (5.19%)  2/76 (2.63%) 
Nervous system disorders         
Peripheral Sensory Neuropathy  1  2/22 (9.09%)  7/28 (25.00%)  10/77 (12.99%)  9/76 (11.84%) 
Headache  1  3/22 (13.64%)  1/28 (3.57%)  7/77 (9.09%)  5/76 (6.58%) 
Dizziness  1  2/22 (9.09%)  1/28 (3.57%)  7/77 (9.09%)  4/76 (5.26%) 
Neuropathy Peripheral  1  1/22 (4.55%)  2/28 (7.14%)  7/77 (9.09%)  9/76 (11.84%) 
Paraesthesia  1  1/22 (4.55%)  2/28 (7.14%)  4/77 (5.19%)  4/76 (5.26%) 
Ageusia  1  0/22 (0.00%)  2/28 (7.14%)  0/77 (0.00%)  0/76 (0.00%) 
Dysgeusia  1  0/22 (0.00%)  2/28 (7.14%)  9/77 (11.69%)  7/76 (9.21%) 
Peripheral Motor Neuropathy  1  0/22 (0.00%)  0/28 (0.00%)  0/77 (0.00%)  4/76 (5.26%) 
Psychiatric disorders         
Anxiety  1  0/22 (0.00%)  3/28 (10.71%)  0/77 (0.00%)  0/76 (0.00%) 
Insomnia  1  0/22 (0.00%)  3/28 (10.71%)  5/77 (6.49%)  5/76 (6.58%) 
Respiratory, thoracic and mediastinal disorders         
Epistaxis  1  5/22 (22.73%)  7/28 (25.00%)  16/77 (20.78%)  5/76 (6.58%) 
Cough  1  5/22 (22.73%)  2/28 (7.14%)  7/77 (9.09%)  5/76 (6.58%) 
Dyspnoea  1  3/22 (13.64%)  4/28 (14.29%)  7/77 (9.09%)  12/76 (15.79%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  7/22 (31.82%)  10/28 (35.71%)  15/77 (19.48%)  21/76 (27.63%) 
Palmar-Plantar Erythrodysaesthesia Syndrome  1  0/22 (0.00%)  3/28 (10.71%)  4/77 (5.19%)  0/76 (0.00%) 
Nail Disorder  1  0/22 (0.00%)  3/28 (10.71%)  5/77 (6.49%)  3/76 (3.95%) 
Rash  1  1/22 (4.55%)  2/28 (7.14%)  7/77 (9.09%)  2/76 (2.63%) 
Dry Skin  1  2/22 (9.09%)  0/28 (0.00%)  7/77 (9.09%)  1/76 (1.32%) 
Erythema  1  0/22 (0.00%)  2/28 (7.14%)  0/77 (0.00%)  0/76 (0.00%) 
Pain Of Skin  1  2/22 (9.09%)  0/28 (0.00%)  0/77 (0.00%)  0/76 (0.00%) 
Rash Maculo-Papular  1  2/22 (9.09%)  0/28 (0.00%)  0/77 (0.00%)  0/76 (0.00%) 
Pruritus  1  0/22 (0.00%)  0/28 (0.00%)  5/77 (6.49%)  1/76 (1.32%) 
Vascular disorders         
Hypertension  1  0/22 (0.00%)  0/28 (0.00%)  4/77 (5.19%)  5/76 (6.58%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.1)
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.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01684878     History of Changes
Other Study ID Numbers: MO28113
2011-005975-17 ( EudraCT Number )
First Submitted: September 11, 2012
First Posted: September 13, 2012
Results First Submitted: October 3, 2016
Results First Posted: November 23, 2016
Last Update Posted: May 23, 2017