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 |
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Recruitment Status :
Active, not recruiting
First Posted : December 4, 2007
Results First Posted : September 13, 2012
Last Update Posted : April 24, 2018
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Sponsor:
Genentech, Inc.
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Genentech, Inc.
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Brief Summary:
This study is a Phase III, randomized, double-blind, placebo-controlled, multicenter international clinical trial. Participants who have HER2-positive metastatic breast cancer (MBC) and have not received chemotherapy or biological therapy (including approved or investigational tyrosine kinase/HER inhibitors or vaccines) for their metastatic disease are eligible for study. Participants could have received one prior hormonal treatment for MBC. Participants may have received systemic breast cancer treatment in the neo-adjuvant or adjuvant setting, provided that the participant has experienced a disease-free interval (DFI) of greater than or equal to (>/=) 12 months from completion of adjuvant systemic treatment (excluding hormonal therapy) to metastatic diagnosis. Participants may have received trastuzumab and/or a taxane during the neo-adjuvant or adjuvant treatment.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Breast Cancer | Drug: Pertuzumab Drug: Placebo Drug: Trastuzumab Drug: Docetaxel | Phase 3 |
Participants will be randomized in 1:1 ratio to receive pertuzumab or placebo along with trastuzumab and docetaxel every 3 weeks (Q3W) in the treatment phase of the study until investigator-assessed radiographic or clinical progressive disease, unmanageable toxicity, or study termination. Participants who were on placebo arm will be offered to receive after completion of treatment phase but participants who discontinue from the study, will not receive pertuzumab during open-label phase.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 808 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III, Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-positive Metastatic Breast Cancer |
| Actual Study Start Date : | February 12, 2008 |
| Actual Primary Completion Date : | May 13, 2011 |
| Estimated Study Completion Date : | October 23, 2018 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Pertuzumab, trastuzumab, docetaxel
Participants will receive pertuzumab on Day 1 of Cycle 1 followed by trastuzumab and then docetaxel on Day 2 of Cycle 1 (1 Cycle length = 21 days). Participants will continue to receive pertuzumab followed by trastuzumab and then docetaxel every 3 weeks (Q3W) for subsequent cycles until investigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity.
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Drug: Pertuzumab
Pertuzumab will be administered as an IV loading dose of 840 milligrams (mg) Q3W on Day 1 of Cycle 1 (1 Cycle length = 21 days), and 420 mg Q3W on Day 1 of subsequent cycles until investigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity.
Other Name: Perjeta; RO4368451 Drug: Trastuzumab Trastuzumab will be administered as an IV loading dose of 8 milligrams per kilogram (mg/kg) Q3W on Day 2 of Cycle 1 (1 Cycle length = 21 days), and 6 mg/kg Q3W on Day 1 of subsequent cycles until investigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity.
Other Name: Herceptin Drug: Docetaxel Docetaxel will be administered as an IV dose of 75 milligrams per square meter (mg/m^2) Q3W on Day 2 of Cycle 1 (1 Cycle length = 21 days), and 75 mg/m^2 (up to 100 mg/m^2 as per treating physician discretion) Q3W on Day 1 of subsequent cycles until investigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity.
Other Name: Taxotere |
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Placebo Comparator: Placebo, trastuzumab, docetaxel
Participants will receive pertuzumab matching placebo on Day 1 of Cycle 1 followed by trastuzumab and then docetaxel on Day 2 of Cycle 1 (1 Cycle length = 21 days). Participants will continue to receive pertuzumab followed by trastuzumab and then docetaxel Q3W for subsequent cycles until nvestigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity.
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Drug: Placebo
Pertuzumab matching placebo will be administered intravenously. Drug: Trastuzumab Trastuzumab will be administered as an IV loading dose of 8 milligrams per kilogram (mg/kg) Q3W on Day 2 of Cycle 1 (1 Cycle length = 21 days), and 6 mg/kg Q3W on Day 1 of subsequent cycles until investigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity.
Other Name: Herceptin Drug: Docetaxel Docetaxel will be administered as an IV dose of 75 milligrams per square meter (mg/m^2) Q3W on Day 2 of Cycle 1 (1 Cycle length = 21 days), and 75 mg/m^2 (up to 100 mg/m^2 as per treating physician discretion) Q3W on Day 1 of subsequent cycles until investigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity.
Other Name: Taxotere |
Primary Outcome Measures :
- 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) ]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.
Secondary Outcome Measures :
- 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) ]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.
- 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) ]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.
- 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) ]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.
- 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) ]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 to Symptom Progression [ Time Frame: Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months) ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and candidate for chemotherapy. Participants with measurable and non-measurable disease are eligible (locally recurrent disease must not be amenable to resection with curative intent; participants with de novo Stage IV disease are eligible)
- HER2-positive MBC
- Left ventricular ejection fraction (LVEF) >/=50 percent (%) at baseline (within 42 days of randomization)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- For women of childbearing potential, agreement to use an effective form of contraception and to continue its use for the duration of study treatment and for 6 months after the last dose of study treatment
Exclusion Criteria:
- History of anti-cancer therapy for MBC (with the exception of one prior hormonal regimen for MBC)
- History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting
- History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of less than (<) 12 months
- History of persistent Grade >/=2 hematologic toxicity resulting from previous adjuvant therapy
- Current peripheral neuropathy of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0, Grade >/=3 at randomization
- History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma
- Current clinical or radiographic evidence of central nervous system (CNS) metastases
- Computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain is mandatory in cases of clinical suspicion of brain metastases
- History of exposure to cumulative doses of anthracyclines
- Current uncontrolled hypertension or unstable angina
- History of congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment
- History of myocardial infarction within 6 months of randomization
- History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
- Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
- Inadequate organ function within 28 days prior to randomization
- Current severe, uncontrolled systemic disease
- Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
- Pregnant or lactating women
- History of receiving any investigational treatment within 28 days of randomization
- Current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
- Receipt of IV antibiotics for infection within 14 days of randomization
- Current chronic daily treatment with corticosteroids (excluding inhaled steroids)
- Known hypersensitivity to any of the study drugs
- Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00567190
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Sponsors and Collaborators
Genentech, Inc.
Hoffmann-La Roche
Investigators
| Study Director: | Ru Walker, M.D. | Genentech, Inc. |
Publications of Results:
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 Posted: | December 4, 2007 Key Record Dates |
| Results First Posted: | September 13, 2012 |
| Last Update Posted: | April 24, 2018 |
| Last Verified: | April 2018 |
| Studies a U.S. FDA-regulated Drug Product: | Yes | |
| Studies a U.S. FDA-regulated Device Product: | No | |
Keywords provided by Genentech, Inc.:
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Herceptin Breast cancer MBC Taxotere HER2 |
HER2 positive breast cancer HER2 + breast cancer HER2-positive HER2-positive metastatic breast cancer |
Additional relevant MeSH terms:
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Docetaxel Pertuzumab |
Trastuzumab Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action |