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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00567190
First received: December 3, 2007
Last updated: April 6, 2016
Last verified: April 2016
Results First Received: August 14, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Metastatic Breast Cancer
Interventions: Drug: Pertuzumab
Drug: Placebo
Drug: Trastuzumab
Drug: Docetaxel

  Participant Flow


  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population

Reporting Groups
  Description
Pertuzumab + Trastuzumab + Docetaxel 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.
Placebo + Trastuzumab + Docetaxel 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 Total of all reporting groups

Baseline Measures
   Pertuzumab + Trastuzumab + Docetaxel   Placebo + Trastuzumab + Docetaxel   Total 
Overall Participants Analyzed 
[Units: Participants]
 402   406   808 
Age 
[Units: Years]
Mean (Standard Deviation)
 53.4  (10.94)   53.5  (11.35)   53.5  (11.14) 
Gender 
[Units: Patients]
     
Female   402   404   806 
Male   0   2   2 


  Outcome Measures
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1.  Primary:   Progression-free Survival (PFS) Determined by an Independent Review Facility   [ Time Frame: Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months) ]

2.  Secondary:   Overall Survival   [ 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) ]

3.  Secondary:   Progression-free Survival (PFS) Determined by the Investigator   [ 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) ]

4.  Secondary:   Objective Response Determined by an Independent Review Facility   [ Time Frame: Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months) ]

5.  Secondary:   Duration of Objective Response Determined by an Independent Review Facility   [ Time Frame: Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months) ]

6.  Secondary:   Time to Symptom Progression   [ Time Frame: Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months) ]


  Serious Adverse Events


  Other Adverse Events
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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).
Additional 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)

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
Placebo + Trastuzumab + Docetaxel 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.
Pertuzumab + Trastuzumab + Docetaxel 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.
Crossover From Placebo to Pertuzumab 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.

Other Adverse Events
    Placebo + Trastuzumab + Docetaxel   Pertuzumab + Trastuzumab + Docetaxel   Crossover From Placebo to Pertuzumab
Total, other (not including serious) adverse events       
# participants affected / at risk   386/396 (97.47%)   400/408 (98.04%)   39/48 (81.25%) 
Blood and lymphatic system disorders       
Neutropenia † 1       
# participants affected / at risk   191/396 (48.23%)   209/408 (51.23%)   0/48 (0.00%) 
Anaemia † 1       
# participants affected / at risk   77/396 (19.44%)   96/408 (23.53%)   5/48 (10.42%) 
Leukopenia † 1       
# participants affected / at risk   82/396 (20.71%)   75/408 (18.38%)   0/48 (0.00%) 
Cardiac disorders       
Left ventricular dysfunction † 1       
# participants affected / at risk   27/396 (6.82%)   22/408 (5.39%)   0/48 (0.00%) 
Eye disorders       
Lacrimation increased † 1       
# participants affected / at risk   55/396 (13.89%)   60/408 (14.71%)   0/48 (0.00%) 
Conjunctivitis † 1       
# participants affected / at risk   17/396 (4.29%)   31/408 (7.60%)   0/48 (0.00%) 
Dry eye † 1       
# participants affected / at risk   8/396 (2.02%)   23/408 (5.64%)   0/48 (0.00%) 
Gastrointestinal disorders       
Diarrhoea † 1       
# participants affected / at risk   193/396 (48.74%)   277/408 (67.89%)   22/48 (45.83%) 
Nausea † 1       
# participants affected / at risk   168/396 (42.42%)   183/408 (44.85%)   4/48 (8.33%) 
Vomiting † 1       
# participants affected / at risk   96/396 (24.24%)   105/408 (25.74%)   5/48 (10.42%) 
Constipation † 1       
# participants affected / at risk   100/396 (25.25%)   65/408 (15.93%)   0/48 (0.00%) 
Stomatitis † 1       
# participants affected / at risk   63/396 (15.91%)   81/408 (19.85%)   3/48 (6.25%) 
Abdominal pain † 1       
# participants affected / at risk   48/396 (12.12%)   62/408 (15.20%)   0/48 (0.00%) 
Dyspepsia † 1       
# participants affected / at risk   48/396 (12.12%)   54/408 (13.24%)   3/48 (6.25%) 
Abdominal pain upper † 1       
# participants affected / at risk   43/396 (10.86%)   43/408 (10.54%)   0/48 (0.00%) 
General disorders       
Fatigue † 1       
# participants affected / at risk   148/396 (37.37%)   154/408 (37.75%)   4/48 (8.33%) 
Asthenia † 1       
# participants affected / at risk   122/396 (30.81%)   112/408 (27.45%)   0/48 (0.00%) 
Oedema peripheral † 1       
# participants affected / at risk   111/396 (28.03%)   98/408 (24.02%)   0/48 (0.00%) 
Mucosal inflammation † 1       
# participants affected / at risk   78/396 (19.70%)   111/408 (27.21%)   0/48 (0.00%) 
Pyrexia † 1       
# participants affected / at risk   72/396 (18.18%)   78/408 (19.12%)   3/48 (6.25%) 
Oedema † 1       
# participants affected / at risk   49/396 (12.37%)   48/408 (11.76%)   0/48 (0.00%) 
Chills † 1       
# participants affected / at risk   15/396 (3.79%)   34/408 (8.33%)   0/48 (0.00%) 
Pain † 1       
# participants affected / at risk   22/396 (5.56%)   26/408 (6.37%)   0/48 (0.00%) 
Chest pain † 1       
# participants affected / at risk   21/396 (5.30%)   14/408 (3.43%)   0/48 (0.00%) 
Influenza like illness † 1       
# participants affected / at risk   9/396 (2.27%)   22/408 (5.39%)   0/48 (0.00%) 
Immune system disorders       
Hypersensitivity † 1       
# participants affected / at risk   21/396 (5.30%)   26/408 (6.37%)   0/48 (0.00%) 
Infections and infestations       
Upper respiratory tract infection † 1       
# participants affected / at risk   57/396 (14.39%)   85/408 (20.83%)   5/48 (10.42%) 
Nasopharyngitis † 1       
# participants affected / at risk   59/396 (14.90%)   69/408 (16.91%)   11/48 (22.92%) 
Urinary tract infection † 1       
# participants affected / at risk   29/396 (7.32%)   36/408 (8.82%)   0/48 (0.00%) 
Paronychia † 1       
# participants affected / at risk   16/396 (4.04%)   31/408 (7.60%)   0/48 (0.00%) 
Influenza † 1       
# participants affected / at risk   22/396 (5.56%)   26/408 (6.37%)   4/48 (8.33%) 
Rhinitis † 1       
# participants affected / at risk   22/396 (5.56%)   20/408 (4.90%)   3/48 (6.25%) 
Investigations       
Weight decreased † 1       
# participants affected / at risk   19/396 (4.80%)   36/408 (8.82%)   0/48 (0.00%) 
Weight increased † 1       
# participants affected / at risk   22/396 (5.56%)   16/408 (3.92%)   0/48 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite † 1       
# participants affected / at risk   106/396 (26.77%)   120/408 (29.41%)   0/48 (0.00%) 
Hypokalaemia † 1       
# participants affected / at risk   21/396 (5.30%)   37/408 (9.07%)   0/48 (0.00%) 
Musculoskeletal and connective tissue disorders       
Myalgia † 1       
# participants affected / at risk   98/396 (24.75%)   98/408 (24.02%)   0/48 (0.00%) 
Arthralgia † 1       
# participants affected / at risk   69/396 (17.42%)   79/408 (19.36%)   3/48 (6.25%) 
Pain in extremity † 1       
# participants affected / at risk   53/396 (13.38%)   73/408 (17.89%)   0/48 (0.00%) 
Back pain † 1       
# participants affected / at risk   48/396 (12.12%)   65/408 (15.93%)   3/48 (6.25%) 
Bone pain † 1       
# participants affected / at risk   34/396 (8.59%)   37/408 (9.07%)   0/48 (0.00%) 
Musculoskeletal pain † 1       
# participants affected / at risk   38/396 (9.60%)   38/408 (9.31%)   0/48 (0.00%) 
Muscle spasms † 1       
# participants affected / at risk   20/396 (5.05%)   42/408 (10.29%)   0/48 (0.00%) 
Nervous system disorders       
Neuropathy peripheral † 1       
# participants affected / at risk   79/396 (19.95%)   91/408 (22.30%)   0/48 (0.00%) 
Headache † 1       
# participants affected / at risk   76/396 (19.19%)   105/408 (25.74%)   6/48 (12.50%) 
Dysgeusia † 1       
# participants affected / at risk   62/396 (15.66%)   75/408 (18.38%)   0/48 (0.00%) 
Peripheral sensory neuropathy † 1       
# participants affected / at risk   59/396 (14.90%)   50/408 (12.25%)   0/48 (0.00%) 
Dizziness † 1       
# participants affected / at risk   53/396 (13.38%)   61/408 (14.95%)   0/48 (0.00%) 
Paraesthesia † 1       
# participants affected / at risk   41/396 (10.35%)   40/408 (9.80%)   0/48 (0.00%) 
Psychiatric disorders       
Insomnia † 1       
# participants affected / at risk   55/396 (13.89%)   64/408 (15.69%)   0/48 (0.00%) 
Depression † 1       
# participants affected / at risk   20/396 (5.05%)   26/408 (6.37%)   0/48 (0.00%) 
Anxiety † 1       
# participants affected / at risk   20/396 (5.05%)   16/408 (3.92%)   0/48 (0.00%) 
Renal and urinary disorders       
Dysuria † 1       
# participants affected / at risk   11/396 (2.78%)   23/408 (5.64%)   0/48 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough † 1       
# participants affected / at risk   79/396 (19.95%)   96/408 (23.53%)   3/48 (6.25%) 
Dyspnoea † 1       
# participants affected / at risk   62/396 (15.66%)   61/408 (14.95%)   0/48 (0.00%) 
Epistaxis † 1       
# participants affected / at risk   35/396 (8.84%)   41/408 (10.05%)   0/48 (0.00%) 
Oropharyngeal pain † 1       
# participants affected / at risk   27/396 (6.82%)   32/408 (7.84%)   0/48 (0.00%) 
Rhinorrhoea † 1       
# participants affected / at risk   23/396 (5.81%)   32/408 (7.84%)   0/48 (0.00%) 
Skin and subcutaneous tissue disorders       
Alopecia † 1       
# participants affected / at risk   240/396 (60.61%)   248/408 (60.78%)   0/48 (0.00%) 
Rash † 1       
# participants affected / at risk   95/396 (23.99%)   153/408 (37.50%)   8/48 (16.67%) 
Nail disorder † 1       
# participants affected / at risk   92/396 (23.23%)   96/408 (23.53%)   0/48 (0.00%) 
Pruritus † 1       
# participants affected / at risk   40/396 (10.10%)   72/408 (17.65%)   0/48 (0.00%) 
Dry skin † 1       
# participants affected / at risk   24/396 (6.06%)   46/408 (11.27%)   3/48 (6.25%) 
Palmar-Plantar erythrodysaesthesia syndrome † 1       
# participants affected / at risk   22/396 (5.56%)   28/408 (6.86%)   0/48 (0.00%) 
Erythema † 1       
# participants affected / at risk   20/396 (5.05%)   24/408 (5.88%)   0/48 (0.00%) 
Vascular disorders       
Hypertension † 1       
# participants affected / at risk   32/396 (8.08%)   45/408 (11.03%)   0/48 (0.00%) 
Hot flush † 1       
# participants affected / at risk   21/396 (5.30%)   23/408 (5.64%)   0/48 (0.00%) 
Lymphoedema † 1       
# participants affected / at risk   16/396 (4.04%)   24/408 (5.88%)   0/48 (0.00%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 16.1



  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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