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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT00567190
First received: December 3, 2007
Last updated: January 22, 2014
Last verified: January 2014
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
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

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.

Participant Flow:   Overall Study
    Pertuzumab + Trastuzumab + Docetaxel     Placebo + Trastuzumab + Docetaxel  
STARTED     402     406  
COMPLETED     315     287  
NOT COMPLETED     87     119  
Death                 69                 96  
Withdrew Consent                 12                 18  
Lost to Follow-up                 6                 5  



  Baseline Characteristics


  Outcome Measures
  Show All Outcome Measures

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

2.  Secondary:   Overall Survival   [ Time Frame: Baseline to data cut-off (up to 3 years, 3 months) ]

3.  Secondary:   Progression-free Survival (PFS) Determined by the Investigator   [ Time Frame: Baseline to data cut-off (up to 3 years, 3 months) ]

4.  Secondary:   Objective Response   [ Time Frame: Baseline to data cut-off (up to 3 years, 3 months) ]

5.  Secondary:   Duration of Objective Response   [ Time Frame: Baseline to data cut-off (up to 3 years, 3 months) ]

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


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame Baseline to data cut-off (up to 3 years, 3 months)
Additional Description Safety analysis population: All patients (Pt) who received any study treatment. Of the Pt who started the study (pertuzumab [Per]=402, placebo[Pla]=406) group, 2 Pt in each group received no treatment, 8 Pla Pt received at least 1 dose of Per, and 1 Per Pt received Pla at every cycle, resulting in Per=407 (402-2+8-1) and Pla=397 (406-2-8+1).

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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.

Other Adverse Events
    Pertuzumab + Trastuzumab + Docetaxel     Placebo + Trastuzumab + Docetaxel  
Total, other (not including serious) adverse events      
# participants affected / at risk     399/407     387/397  
Blood and lymphatic system disorders      
Neutropenia † 1    
# participants affected / at risk     206/407 (50.61%)     190/397 (47.86%)  
Anaemia † 1    
# participants affected / at risk     92/407 (22.60%)     74/397 (18.64%)  
Leukopenia † 1    
# participants affected / at risk     74/407 (18.18%)     81/397 (20.40%)  
Cardiac disorders      
Left ventricular dysfunction † 1    
# participants affected / at risk     15/407 (3.69%)     26/397 (6.55%)  
Eye disorders      
Lacrimation increased † 1    
# participants affected / at risk     57/407 (14.00%)     55/397 (13.85%)  
Conjunctivitis † 1    
# participants affected / at risk     23/407 (5.65%)     17/397 (4.28%)  
Gastrointestinal disorders      
Diarrhoea † 1    
# participants affected / at risk     270/407 (66.34%)     184/397 (46.35%)  
Nausea † 1    
# participants affected / at risk     172/407 (42.26%)     165/397 (41.56%)  
Vomiting † 1    
# participants affected / at risk     97/407 (23.83%)     94/397 (23.68%)  
Constipation † 1    
# participants affected / at risk     61/407 (14.99%)     98/397 (24.69%)  
Stomatitis † 1    
# participants affected / at risk     77/407 (18.92%)     61/397 (15.37%)  
Abdominal pain † 1    
# participants affected / at risk     57/407 (14.00%)     48/397 (12.09%)  
Dyspepsia † 1    
# participants affected / at risk     49/407 (12.04%)     48/397 (12.09%)  
Abdominal pain upper † 1    
# participants affected / at risk     37/407 (9.09%)     39/397 (9.82%)  
General disorders      
Fatigue † 1    
# participants affected / at risk     152/407 (37.35%)     146/397 (36.78%)  
Asthenia † 1    
# participants affected / at risk     105/407 (25.80%)     120/397 (30.23%)  
Oedema peripheral † 1    
# participants affected / at risk     94/407 (23.10%)     119/397 (29.97%)  
Mucosal inflammation † 1    
# participants affected / at risk     113/407 (27.76%)     78/397 (19.65%)  
Pyrexia † 1    
# participants affected / at risk     72/407 (17.69%)     71/397 (17.88%)  
Oedema † 1    
# participants affected / at risk     46/407 (11.30%)     50/397 (12.59%)  
Chills † 1    
# participants affected / at risk     33/407 (8.11%)     15/397 (3.78%)  
Pain † 1    
# participants affected / at risk     24/407 (5.90%)     22/397 (5.54%)  
Immune system disorders      
Hypersensitivity † 1    
# participants affected / at risk     24/407 (5.90%)     20/397 (5.04%)  
Infections and infestations      
Upper respiratory tract infection † 1    
# participants affected / at risk     68/407 (16.71%)     53/397 (13.35%)  
Nasophayrngitis † 1    
# participants affected / at risk     48/407 (11.79%)     51/397 (12.85%)  
Urinary tract infection † 1    
# participants affected / at risk     30/407 (7.37%)     29/397 (7.30%)  
Paronychia † 1    
# participants affected / at risk     29/407 (7.13%)     14/397 (3.53%)  
Investigations      
Weight decreased † 1    
# participants affected / at risk     34/407 (8.35%)     16/397 (4.03%)  
Weight increased † 1    
# participants affected / at risk     13/407 (3.19%)     21/397 (5.29%)  
Metabolism and nutrition disorders      
Decreased appetite † 1    
# participants affected / at risk     118/407 (28.99%)     105/397 (26.45%)  
Hypokalaemia † 1    
# participants affected / at risk     37/407 (9.09%)     19/397 (4.79%)  
Musculoskeletal and connective tissue disorders      
Myalgia † 1    
# participants affected / at risk     92/407 (22.60%)     94/397 (23.68%)  
Arthralgia † 1    
# participants affected / at risk     63/407 (15.48%)     64/397 (16.12%)  
Pain in extremity † 1    
# participants affected / at risk     62/407 (15.23%)     47/397 (11.84%)  
Back pain † 1    
# participants affected / at risk     53/407 (13.02%)     46/397 (11.59%)  
Bone pain † 1    
# participants affected / at risk     39/407 (9.58%)     39/397 (9.82%)  
Musculoskeletal pain † 1    
# participants affected / at risk     32/407 (7.86%)     35/397 (8.82%)  
Muscle spasms † 1    
# participants affected / at risk     29/407 (7.13%)     15/397 (3.78%)  
Nervous system disorders      
Neuropathy peripheral † 1    
# participants affected / at risk     86/407 (21.13%)     80/397 (20.15%)  
Headache † 1    
# participants affected / at risk     85/407 (20.88%)     67/397 (16.88%)  
Dysgeusia † 1    
# participants affected / at risk     75/407 (18.43%)     62/397 (15.62%)  
Peripheral sensory neuropathy † 1    
# participants affected / at risk     49/407 (12.04%)     56/397 (14.11%)  
Dizziness † 1    
# participants affected / at risk     51/407 (12.53%)     48/397 (12.09%)  
Paraesthesia † 1    
# participants affected / at risk     37/407 (9.09%)     40/397 (10.08%)  
Psychiatric disorders      
Insomnia † 1    
# participants affected / at risk     54/407 (13.27%)     53/397 (13.35%)  
Depression † 1    
# participants affected / at risk     23/407 (5.65%)     19/397 (4.79%)  
Renal and urinary disorders      
Dysuria † 1    
# participants affected / at risk     22/407 (5.41%)     9/397 (2.27%)  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     87/407 (21.38%)     74/397 (18.64%)  
Dyspnoea † 1    
# participants affected / at risk     56/407 (13.76%)     61/397 (15.37%)  
Epistaxis † 1    
# participants affected / at risk     37/407 (9.09%)     34/397 (8.56%)  
Oropharyngeal pain † 1    
# participants affected / at risk     27/407 (6.63%)     25/397 (6.30%)  
Rhinorrhoea † 1    
# participants affected / at risk     26/407 (6.39%)     21/397 (5.29%)  
Pleural effusion † 1    
# participants affected / at risk     19/407 (4.67%)     20/397 (5.04%)  
Skin and subcutaneous tissue disorders      
Alopecia † 1    
# participants affected / at risk     248/407 (60.93%)     240/397 (60.45%)  
Rash † 1    
# participants affected / at risk     137/407 (33.66%)     96/397 (24.18%)  
Nail disorder † 1    
# participants affected / at risk     93/407 (22.85%)     91/397 (22.92%)  
Pruritus † 1    
# participants affected / at risk     57/407 (14.00%)     40/397 (10.08%)  
Dry skin † 1    
# participants affected / at risk     43/407 (10.57%)     17/397 (4.28%)  
Palmar-Plantar erythrodysaesthesia syndrome † 1    
# participants affected / at risk     28/407 (6.88%)     22/397 (5.54%)  
Erythema † 1    
# participants affected / at risk     22/407 (5.41%)     19/397 (4.79%)  
Vascular disorders      
Hypertension † 1    
# participants affected / at risk     37/407 (9.09%)     31/397 (7.81%)  
Hot flush † 1    
# participants affected / at risk     21/407 (5.16%)     21/397 (5.29%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (14.0)



  Limitations and Caveats
  Hide Limitations and Caveats

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
The survival data at the time of the data cut-off were not mature.


  More Information