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A Study to Evaluate Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-positive Metastatic Breast Cancer (CLEOPATRA)

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ClinicalTrials.gov Identifier: NCT00567190
Recruitment Status : Completed
First Posted : December 4, 2007
Results First Posted : September 13, 2012
Last Update Posted : January 8, 2019
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Metastatic Breast Cancer
Interventions Drug: Pertuzumab
Drug: Placebo
Drug: Trastuzumab
Drug: Docetaxel
Enrollment 808
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Pertuzumab + Trastuzumab + Docetaxel Placebo + Trastuzumab + Docetaxel
Hide Arm/Group Description Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles. Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Period Title: Overall Study
Started 402 [1] 406 [1]
Completed 192 [2] 142 [3]
Not Completed 210 264
Reason Not Completed
Death             168             221
Withdrew Consent or Lost to Follow-up             42             43
[1]
All randomized patients (Intent-to-Treat [ITT]) population
[2]
On 11 February 2014, 67 were alive and on study treatment; 125 were alive and in survival follow-up
[3]
On 11 February 2014, 37 were alive and on study treatment; 105 were alive and in survival follow-up
Arm/Group Title Pertuzumab + Trastuzumab + Docetaxel Placebo + Trastuzumab + Docetaxel Total
Hide Arm/Group Description Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles. Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles. Total of all reporting groups
Overall Number of Baseline Participants 402 406 808
Hide Baseline Analysis Population Description
ITT population
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 402 participants 406 participants 808 participants
53.4  (10.94) 53.5  (11.35) 53.5  (11.14)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 402 participants 406 participants 808 participants
Female
402
 100.0%
404
  99.5%
806
  99.8%
Male
0
   0.0%
2
   0.5%
2
   0.2%
1.Primary Outcome
Title Progression-free Survival (PFS) Determined by an Independent Review Facility
Hide Description PFS was defined as the time from randomization to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors (RECIST) or death from any cause (within 18 weeks of last tumor assessment), whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions were selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, were identified as target lesions.
Time Frame Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: All randomized patients.
Arm/Group Title Pertuzumab + Trastuzumab + Docetaxel Placebo + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Overall Number of Participants Analyzed 402 406
Median (95% Confidence Interval)
Unit of Measure: Months
18.5
(15.0 to 23.0)
12.4
(10.0 to 13.0)
2.Secondary Outcome
Title Overall Survival
Hide Description Overall survival was defined as the time from randomization to death from any cause. The median and 95 percent (%) confidence interval (CI) for time to event were estimated using Kaplan-Meier methodology.
Time Frame Baseline to the third data cut-off (11 February 2014) at 389 deaths (approximately 43 months after enrollment of the last patient, up to 6 years overall)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized patients.
Arm/Group Title Pertuzumab + Trastuzumab + Docetaxel Placebo + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Overall Number of Participants Analyzed 402 406
Median (95% Confidence Interval)
Unit of Measure: Months
56.5 [1] 
(49.0 to NA)
40.8
(36.0 to 48.0)
[1]
The upper limit of the 95% CI could not be determined as it was larger than the maximum follow-up time.
3.Secondary Outcome
Title Progression-free Survival (PFS) Determined by the Investigator
Hide Description PFS was defined as the time from randomization to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors (RECIST) or death from any cause (within 18 weeks of last tumor assessment), whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions were selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, were identified as target lesions.
Time Frame Baseline to the third data cut-off (11 February 2014) at 389 deaths (approximately 43 months after enrollment of the last patient, up to 6 years overall)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized patients.
Arm/Group Title Pertuzumab + Trastuzumab + Docetaxel Placebo + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Overall Number of Participants Analyzed 402 406
Median (95% Confidence Interval)
Unit of Measure: Months
18.7
(17.0 to 22.0)
12.4
(10.0 to 14.0)
4.Secondary Outcome
Title Objective Response Determined by an Independent Review Facility
Hide Description A patient had an objective response if they had a complete response or a partial response determined on two consecutive occasions ≥ 4 weeks apart as determined by the investigator using RECIST. For target lesions, a complete response was defined as the disappearance of all target lesions; a partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. For non-target lesions, a complete response was defined as the disappearance of all non-target lesions; a partial response was defined as the persistence of 1 or more non-target lesions.
Time Frame Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized patients. Only patients with measurable disease at baseline were included in the analysis.
Arm/Group Title Pertuzumab + Trastuzumab + Docetaxel Placebo + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Overall Number of Participants Analyzed 343 336
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
80.2
(75.6 to 84.3)
69.3
(64.1 to 74.2)
5.Secondary Outcome
Title Duration of Objective Response Determined by an Independent Review Facility
Hide Description Duration of objective response was defined as the time from the initial response to documented disease progression or death from any cause, whichever occurred first.
Time Frame Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized patients. Only patients with an objective response were included in the analysis.
Arm/Group Title Pertuzumab + Trastuzumab + Docetaxel Placebo + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Overall Number of Participants Analyzed 275 233
Median (95% Confidence Interval)
Unit of Measure: Weeks
87.6
(71.0 to 106.0)
54.1
(46.0 to 64.0)
6.Secondary Outcome
Title Time to Symptom Progression
Hide Description Time to symptom progression was defined as the time from randomization to the first symptom progression as measured by the Functional Assessment of Cancer Therapy-for patients with Breast Cancer (FACT-B) questionnaire with the Trial Outcomes Index-Physical/Functional/Breast (TOI-PFB) subscale. The FACT-B TOI-PFB subscale contains 24 items from 3 subsections of the FACT-B questionnaire: Physical well-being, functional well-being, and additional concerns for breast cancer patients (breast cancer subscale [BCS]). All items in the questionnaire were rated by the patient on a 5-point scale ranging from 0 (“not at all”) to 4 (“very much”). The total score ranged from 0 to 96. A higher score indicates better perceived quality of life. A positive change score from baseline indicates improvement. Symptom progression was defined as a decrease from baseline of 5 points or more.
Time Frame Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized patients. Only female patients were included in the analysis.
Arm/Group Title Pertuzumab + Trastuzumab + Docetaxel Placebo + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Overall Number of Participants Analyzed 402 404
Median (95% Confidence Interval)
Unit of Measure: Weeks
18.4
(18.0 to 27.0)
18.3
(18.0 to 27.0)
Time Frame First treatment dose (12 February 2008) through final data analysis cut-off (11 February 2014) for a total safety analysis time frame of 6 years. The AE data derived from a snapshot taken on 24 March 2014 of the final analysis dataset (11 February 2014).
Adverse Event Reporting Description Of those who started the study (pertuzumab [Ptz]=402, placebo[Pla]=406), 2 patients in each group received no treatment (total of 4), 9 Pla patients received at least 1 dose of Ptz, 1 Ptz patient received Pla at every cycle; resulting in Ptz=408 (402-2+9-1) and Pla=396 (406-2-9+1)
 
Arm/Group Title Placebo + Trastuzumab + Docetaxel Pertuzumab + Trastuzumab + Docetaxel Crossover From Placebo to Pertuzumab
Hide Arm/Group Description Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles. For the 48 patients that crossed over to the pertuzumab treatment group, AEs were analyzed from the day of their first placebo dose (Day 1) through the day just prior to their first pertuzumab dose. Any AEs occurring on, or after, the day of their first dose of pertuzumab were included in the Crossover treatment group analysis. Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles. Forty-eight of 406 patients (11.8%) randomized to the placebo treatment group whose disease had not progressed crossed over to an open-label pertuzumab treatment group between July 2012 and November 2012. Patients received pertuzumab administered as an IV loading dose of 840 mg at cycle 1 then 420 mg IV every q3w until investigator-assessed radiographic or clinical evidence of PD, unacceptable toxicity, or withdrawal of consent. Trastuzumab and docetaxel doses continued in accordance with the pre-crossover placebo treatment regimens and according to dosing specifications indicated in the study protocol.
All-Cause Mortality
Placebo + Trastuzumab + Docetaxel Pertuzumab + Trastuzumab + Docetaxel Crossover From Placebo to Pertuzumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo + Trastuzumab + Docetaxel Pertuzumab + Trastuzumab + Docetaxel Crossover From Placebo to Pertuzumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   116/396 (29.29%)   149/408 (36.52%)   6/48 (12.50%) 
Blood and lymphatic system disorders       
Anaemia  1  3/396 (0.76%)  3/408 (0.74%)  1/48 (2.08%) 
Febrile neutropenia  1  20/396 (5.05%)  46/408 (11.27%)  0/48 (0.00%) 
Granulocytopenia  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Leukopenia  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Neutropenia  1  19/396 (4.80%)  18/408 (4.41%)  0/48 (0.00%) 
Cardiac disorders       
Atrial fibrillation  1  3/396 (0.76%)  0/408 (0.00%)  0/48 (0.00%) 
Cardiac failure congestive  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Coronary artery disease  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Left ventricular dysfunction  1  7/396 (1.77%)  6/408 (1.47%)  0/48 (0.00%) 
Myocardial infarction  1  3/396 (0.76%)  0/408 (0.00%)  0/48 (0.00%) 
Myocardial ischaemia  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Ventricular fibrillation  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Eye disorders       
Cataract  1  0/396 (0.00%)  2/408 (0.49%)  0/48 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Colitis  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Constipation  1  2/396 (0.51%)  0/408 (0.00%)  0/48 (0.00%) 
Diarrhoea  1  5/396 (1.26%)  13/408 (3.19%)  1/48 (2.08%) 
Duodenal ulcer  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Duodenal ulcer haemorrhage  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Enteritis  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Gastrointestinal haemorrhage  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Haemorrhoidal haemorrhage  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Haemorrhoids  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Intestinal ischaemia  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Intestinal obstruction  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Intestinal perforation  1  2/396 (0.51%)  0/408 (0.00%)  0/48 (0.00%) 
Lower gastrointestinal haemorrhage  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Nausea  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Oesophagitis  1  0/396 (0.00%)  2/408 (0.49%)  0/48 (0.00%) 
Rectal haemorrhage  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Upper gastrointestinal haemorrhage  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Vomiting  1  1/396 (0.25%)  2/408 (0.49%)  0/48 (0.00%) 
General disorders       
Drowning  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Asthenia  1  0/396 (0.00%)  2/408 (0.49%)  0/48 (0.00%) 
Chest pain  1  2/396 (0.51%)  1/408 (0.25%)  0/48 (0.00%) 
Death  1  0/396 (0.00%)  1/408 (0.25%)  1/48 (2.08%) 
Fatigue  1  1/396 (0.25%)  2/408 (0.49%)  0/48 (0.00%) 
General physical health deterioration  1  2/396 (0.51%)  0/408 (0.00%)  0/48 (0.00%) 
Influenza like illness  1  0/396 (0.00%)  2/408 (0.49%)  0/48 (0.00%) 
Mucosal inflammation  1  1/396 (0.25%)  1/408 (0.25%)  0/48 (0.00%) 
Pyrexia  1  3/396 (0.76%)  6/408 (1.47%)  1/48 (2.08%) 
Hepatobiliary disorders       
Cholecystitis acute  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Cholelithiasis  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Hepatic failure  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Immune system disorders       
Anaphylactic reaction  1  1/396 (0.25%)  1/408 (0.25%)  0/48 (0.00%) 
Drug hypersensitivity  1  3/396 (0.76%)  3/408 (0.74%)  0/48 (0.00%) 
Hypersensitivity  1  0/396 (0.00%)  3/408 (0.74%)  0/48 (0.00%) 
Infections and infestations       
Acute sinusitis  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Anal abscess  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Appendicitis  1  0/396 (0.00%)  2/408 (0.49%)  0/48 (0.00%) 
Breast abscess  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Breast cellulitis  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Bronchopneumonia  1  2/396 (0.51%)  0/408 (0.00%)  0/48 (0.00%) 
Campylobacter gastroenteritis  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Catheter site infection  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Cellulitis  1  2/396 (0.51%)  10/408 (2.45%)  0/48 (0.00%) 
Cellulitis gangrenous  1  0/396 (0.00%)  0/408 (0.00%)  1/48 (2.08%) 
Clostridium difficile colitis  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Coccidioidomycosis  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Device related infection  1  1/396 (0.25%)  2/408 (0.49%)  0/48 (0.00%) 
Diarrhoea infectious  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Erysipelas  1  0/396 (0.00%)  2/408 (0.49%)  0/48 (0.00%) 
Gastroenteritis  1  2/396 (0.51%)  2/408 (0.49%)  0/48 (0.00%) 
Gastrointestinal infection  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
H1N1 influenza  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Herpes zoster  1  3/396 (0.76%)  1/408 (0.25%)  0/48 (0.00%) 
Infection  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Lower respiratory tract infection  1  0/396 (0.00%)  4/408 (0.98%)  0/48 (0.00%) 
Lymph node tuberculosis  1  0/396 (0.00%)  0/408 (0.00%)  1/48 (2.08%) 
Neutropenic infection  1  1/396 (0.25%)  4/408 (0.98%)  0/48 (0.00%) 
Neutropenic sepsis  1  2/396 (0.51%)  0/408 (0.00%)  0/48 (0.00%) 
Onychomycosis  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Oral candidiasis  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Osteomyelitis  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Osteomyelitis chronic  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Pharyngitis  1  0/396 (0.00%)  2/408 (0.49%)  0/48 (0.00%) 
Pneumonia  1  9/396 (2.27%)  5/408 (1.23%)  1/48 (2.08%) 
Pneumonia staphylococcal  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Postoperative wound infection  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Pyelonephritis acute  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Rash pustular  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Respiratory tract infection  1  1/396 (0.25%)  1/408 (0.25%)  0/48 (0.00%) 
Respiratory tract infection viral  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Sepsis  1  3/396 (0.76%)  1/408 (0.25%)  0/48 (0.00%) 
Sepsis syndrome  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Septic shock  1  1/396 (0.25%)  1/408 (0.25%)  0/48 (0.00%) 
Skin infection  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Soft tissue infection  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Upper respiratory tract infection  1  0/396 (0.00%)  2/408 (0.49%)  0/48 (0.00%) 
Urinary tract infection  1  1/396 (0.25%)  3/408 (0.74%)  0/48 (0.00%) 
Urosepsis  1  0/396 (0.00%)  2/408 (0.49%)  0/48 (0.00%) 
Viral infection  1  2/396 (0.51%)  0/408 (0.00%)  0/48 (0.00%) 
Wound infection  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Wound infection staphylococcal  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Injury, poisoning and procedural complications       
Compression fracture  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Contusion  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Femur fracture  1  1/396 (0.25%)  3/408 (0.74%)  0/48 (0.00%) 
Fracture  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Post procedural discomfort  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Scapula fracture  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Tendon injury  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Thermal burn  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Tibia fracture  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Investigations       
Blood electrolytes abnormal  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Blood glucose increased  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Ejection fracture decreased  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Dehydration  1  2/396 (0.51%)  1/408 (0.25%)  1/48 (2.08%) 
Diabetes mellitus  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Fluid retention  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Hyperglycaemia  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Hypoglycaemia  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  1/396 (0.25%)  2/408 (0.49%)  0/48 (0.00%) 
Mobility decreased  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Muscular weakness  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Myalgia  1  1/396 (0.25%)  1/408 (0.25%)  0/48 (0.00%) 
Neck pain  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Osteonecrosis of jaw  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Colon cancer  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Endometrial cancer  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Glioblastoma multiforme  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Ocular neoplasm  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Pituitary tumour benign  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Tumour haemorrhage  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Uterine leiomyoma  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Nervous system disorders       
Cerebrovascular accident  1  1/396 (0.25%)  1/408 (0.25%)  0/48 (0.00%) 
Convulsion  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Monoparesis  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Peripheral sensorimotor neuropathy  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Somnolence  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Spinal cord compression  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Syncope  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
VIIth nerve paralysis  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Psychiatric disorders       
Suicide attempt  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Renal and urinary disorders       
Acute prerenal failure  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Haematuria  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Nephrolithiasis  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Renal failure  1  1/396 (0.25%)  1/408 (0.25%)  0/48 (0.00%) 
Renal failure acute  1  2/396 (0.51%)  0/408 (0.00%)  0/48 (0.00%) 
Renal failure chronic  1  0/396 (0.00%)  0/408 (0.00%)  1/48 (2.08%) 
Reproductive system and breast disorders       
Breast haemorrhage  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Metrorrhagia  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Vaginal haemorrhage  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Asthma  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Dyspnoea  1  2/396 (0.51%)  2/408 (0.49%)  0/48 (0.00%) 
Haemoptysis  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Interstitial lung disease  1  0/396 (0.00%)  2/408 (0.49%)  0/48 (0.00%) 
Pleural effusion  1  4/396 (1.01%)  2/408 (0.49%)  0/48 (0.00%) 
Pneumonia aspiration  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Pneumonitis  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Pneumothorax  1  1/396 (0.25%)  1/408 (0.25%)  0/48 (0.00%) 
Pulmonary embolism  1  0/396 (0.00%)  5/408 (1.23%)  0/48 (0.00%) 
Respiratory failure  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Skin and subcutaneous tissue disorders       
Dermatitis allergic  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Drug eruption  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Rash maculo-papular  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Surgical and medical procedures       
Abortion induced  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Vascular disorders       
Aortic stenosis  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Deep vein thrombosis  1  0/396 (0.00%)  3/408 (0.74%)  0/48 (0.00%) 
Haematoma  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Hypertension  1  1/396 (0.25%)  1/408 (0.25%)  0/48 (0.00%) 
Hypertensive crisis  1  1/396 (0.25%)  0/408 (0.00%)  0/48 (0.00%) 
Hypotension  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Venous thrombosis limb  1  0/396 (0.00%)  1/408 (0.25%)  0/48 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + Trastuzumab + Docetaxel Pertuzumab + Trastuzumab + Docetaxel Crossover From Placebo to Pertuzumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   386/396 (97.47%)   400/408 (98.04%)   39/48 (81.25%) 
Blood and lymphatic system disorders       
Neutropenia  1  191/396 (48.23%)  209/408 (51.23%)  0/48 (0.00%) 
Anaemia  1  77/396 (19.44%)  96/408 (23.53%)  5/48 (10.42%) 
Leukopenia  1  82/396 (20.71%)  75/408 (18.38%)  0/48 (0.00%) 
Cardiac disorders       
Left ventricular dysfunction  1  27/396 (6.82%)  22/408 (5.39%)  0/48 (0.00%) 
Eye disorders       
Lacrimation increased  1  55/396 (13.89%)  60/408 (14.71%)  0/48 (0.00%) 
Conjunctivitis  1  17/396 (4.29%)  31/408 (7.60%)  0/48 (0.00%) 
Dry eye  1  8/396 (2.02%)  23/408 (5.64%)  0/48 (0.00%) 
Gastrointestinal disorders       
Diarrhoea  1  193/396 (48.74%)  277/408 (67.89%)  22/48 (45.83%) 
Nausea  1  168/396 (42.42%)  183/408 (44.85%)  4/48 (8.33%) 
Vomiting  1  96/396 (24.24%)  105/408 (25.74%)  5/48 (10.42%) 
Constipation  1  100/396 (25.25%)  65/408 (15.93%)  0/48 (0.00%) 
Stomatitis  1  63/396 (15.91%)  81/408 (19.85%)  3/48 (6.25%) 
Abdominal pain  1  48/396 (12.12%)  62/408 (15.20%)  0/48 (0.00%) 
Dyspepsia  1  48/396 (12.12%)  54/408 (13.24%)  3/48 (6.25%) 
Abdominal pain upper  1  43/396 (10.86%)  43/408 (10.54%)  0/48 (0.00%) 
General disorders       
Fatigue  1  148/396 (37.37%)  154/408 (37.75%)  4/48 (8.33%) 
Asthenia  1  122/396 (30.81%)  112/408 (27.45%)  0/48 (0.00%) 
Oedema peripheral  1  111/396 (28.03%)  98/408 (24.02%)  0/48 (0.00%) 
Mucosal inflammation  1  78/396 (19.70%)  111/408 (27.21%)  0/48 (0.00%) 
Pyrexia  1  72/396 (18.18%)  78/408 (19.12%)  3/48 (6.25%) 
Oedema  1  49/396 (12.37%)  48/408 (11.76%)  0/48 (0.00%) 
Chills  1  15/396 (3.79%)  34/408 (8.33%)  0/48 (0.00%) 
Pain  1  22/396 (5.56%)  26/408 (6.37%)  0/48 (0.00%) 
Chest pain  1  21/396 (5.30%)  14/408 (3.43%)  0/48 (0.00%) 
Influenza like illness  1  9/396 (2.27%)  22/408 (5.39%)  0/48 (0.00%) 
Immune system disorders       
Hypersensitivity  1  21/396 (5.30%)  26/408 (6.37%)  0/48 (0.00%) 
Infections and infestations       
Upper respiratory tract infection  1  57/396 (14.39%)  85/408 (20.83%)  5/48 (10.42%) 
Nasopharyngitis  1  59/396 (14.90%)  69/408 (16.91%)  11/48 (22.92%) 
Urinary tract infection  1  29/396 (7.32%)  36/408 (8.82%)  0/48 (0.00%) 
Paronychia  1  16/396 (4.04%)  31/408 (7.60%)  0/48 (0.00%) 
Influenza  1  22/396 (5.56%)  26/408 (6.37%)  4/48 (8.33%) 
Rhinitis  1  22/396 (5.56%)  20/408 (4.90%)  3/48 (6.25%) 
Investigations       
Weight decreased  1  19/396 (4.80%)  36/408 (8.82%)  0/48 (0.00%) 
Weight increased  1  22/396 (5.56%)  16/408 (3.92%)  0/48 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  106/396 (26.77%)  120/408 (29.41%)  0/48 (0.00%) 
Hypokalaemia  1  21/396 (5.30%)  37/408 (9.07%)  0/48 (0.00%) 
Musculoskeletal and connective tissue disorders       
Myalgia  1  98/396 (24.75%)  98/408 (24.02%)  0/48 (0.00%) 
Arthralgia  1  69/396 (17.42%)  79/408 (19.36%)  3/48 (6.25%) 
Pain in extremity  1  53/396 (13.38%)  73/408 (17.89%)  0/48 (0.00%) 
Back pain  1  48/396 (12.12%)  65/408 (15.93%)  3/48 (6.25%) 
Bone pain  1  34/396 (8.59%)  37/408 (9.07%)  0/48 (0.00%) 
Musculoskeletal pain  1  38/396 (9.60%)  38/408 (9.31%)  0/48 (0.00%) 
Muscle spasms  1  20/396 (5.05%)  42/408 (10.29%)  0/48 (0.00%) 
Nervous system disorders       
Neuropathy peripheral  1  79/396 (19.95%)  91/408 (22.30%)  0/48 (0.00%) 
Headache  1  76/396 (19.19%)  105/408 (25.74%)  6/48 (12.50%) 
Dysgeusia  1  62/396 (15.66%)  75/408 (18.38%)  0/48 (0.00%) 
Peripheral sensory neuropathy  1  59/396 (14.90%)  50/408 (12.25%)  0/48 (0.00%) 
Dizziness  1  53/396 (13.38%)  61/408 (14.95%)  0/48 (0.00%) 
Paraesthesia  1  41/396 (10.35%)  40/408 (9.80%)  0/48 (0.00%) 
Psychiatric disorders       
Insomnia  1  55/396 (13.89%)  64/408 (15.69%)  0/48 (0.00%) 
Depression  1  20/396 (5.05%)  26/408 (6.37%)  0/48 (0.00%) 
Anxiety  1  20/396 (5.05%)  16/408 (3.92%)  0/48 (0.00%) 
Renal and urinary disorders       
Dysuria  1  11/396 (2.78%)  23/408 (5.64%)  0/48 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  79/396 (19.95%)  96/408 (23.53%)  3/48 (6.25%) 
Dyspnoea  1  62/396 (15.66%)  61/408 (14.95%)  0/48 (0.00%) 
Epistaxis  1  35/396 (8.84%)  41/408 (10.05%)  0/48 (0.00%) 
Oropharyngeal pain  1  27/396 (6.82%)  32/408 (7.84%)  0/48 (0.00%) 
Rhinorrhoea  1  23/396 (5.81%)  32/408 (7.84%)  0/48 (0.00%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  240/396 (60.61%)  248/408 (60.78%)  0/48 (0.00%) 
Rash  1  95/396 (23.99%)  153/408 (37.50%)  8/48 (16.67%) 
Nail disorder  1  92/396 (23.23%)  96/408 (23.53%)  0/48 (0.00%) 
Pruritus  1  40/396 (10.10%)  72/408 (17.65%)  0/48 (0.00%) 
Dry skin  1  24/396 (6.06%)  46/408 (11.27%)  3/48 (6.25%) 
Palmar-Plantar erythrodysaesthesia syndrome  1  22/396 (5.56%)  28/408 (6.86%)  0/48 (0.00%) 
Erythema  1  20/396 (5.05%)  24/408 (5.88%)  0/48 (0.00%) 
Vascular disorders       
Hypertension  1  32/396 (8.08%)  45/408 (11.03%)  0/48 (0.00%) 
Hot flush  1  21/396 (5.30%)  23/408 (5.64%)  0/48 (0.00%) 
Lymphoedema  1  16/396 (4.04%)  24/408 (5.88%)  0/48 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
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: Genentech, Inc.
Phone: 800 821-8590
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00567190     History of Changes
Other Study ID Numbers: TOC4129g
WO20698 ( Other Identifier: Hoffmann-La Roche )
2007-002997-72 ( EudraCT Number )
First Submitted: December 3, 2007
First Posted: December 4, 2007
Results First Submitted: August 14, 2012
Results First Posted: September 13, 2012
Last Update Posted: January 8, 2019