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:
Genentech, Inc.
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
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Purpose
This study is a Phase III, randomized, double-blind, placebo-controlled, multicenter international clinical trial. Patients who have human epidermal growth factor receptor 2 (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. Patients could have received one prior hormonal treatment for MBC. Patients may have received systemic breast cancer treatment in the neo-adjuvant or adjuvant setting, provided that the patient has experienced a disease-free interval (DFI) of ≥ 12 months from completion of adjuvant systemic treatment (excluding hormonal therapy) to metastatic diagnosis. Patients may have received trastuzumab and/or a taxane during the neo-adjuvant or adjuvant treatment.
| Condition | Intervention | Phase |
|---|---|---|
|
Metastatic Breast Cancer |
Drug: Pertuzumab Drug: Placebo Drug: Trastuzumab Drug: Docetaxel |
Phase 3 |
| 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 |
| 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 |
Resource links provided by NLM:
Further study details as provided by Genentech, Inc.:
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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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.
| Enrollment: | 808 |
| Study Start Date: | February 2008 |
| Estimated Study Completion Date: | July 2017 |
| Primary Completion Date: | May 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Pertuzumab + trastuzumab + docetaxel
Participants 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.
|
Drug: Pertuzumab
Participants received a loading dose of 840 mg IV.
Other Name: Perjeta
Drug: Trastuzumab
Participants received a loading dose of 8 mg/kg IV.
Other Name: Herceptin
Drug: Docetaxel
At the investigator's discretion, the docetaxel dose could be increased to 100 mg/m^2 for participants who tolerated at least 1 cycle without significant toxicities.
Other Name: Taxotere
|
|
Placebo Comparator: Placebo + trastuzumab + docetaxel
Participants received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
|
Drug: Placebo
Drug: Trastuzumab
Participants received a loading dose of 8 mg/kg IV.
Other Name: Herceptin
Drug: Docetaxel
At the investigator's discretion, the docetaxel dose could be increased to 100 mg/m^2 for participants who tolerated at least 1 cycle without significant toxicities.
Other Name: Taxotere
|
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Genders Eligible for Study: | Both |
| 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. Patients with measurable and non-measurable disease are eligible (locally recurrent disease must not be amenable to resection with curative intent; patients with de novo Stage IV disease are eligible).
- Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC).
- Age ≥ 18 years.
- Left ventricular ejection fraction (LVEF) ≥ 50% 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.
- Signed, written informed consent obtained prior to any study procedure.
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 < 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 intravenous (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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00567190
Please refer to this study by its ClinicalTrials.gov identifier: NCT00567190
Sponsors and Collaborators
Genentech, Inc.
Hoffmann-La Roche
Investigators
| Study Director: | Ru Walker, M.D. | Genentech, Inc. |
More Information
Publications:
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 |
| Study First Received: | December 3, 2007 |
| Results First Received: | August 14, 2012 |
| Last Updated: | April 6, 2016 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Genentech, Inc.:
|
Herceptin Breast cancer MBC Taxotere HER2 |
HER2 positive breast cancer HER2 + breast cancer HER2-positive HER2-positive metastatic breast cancer |
Additional relevant MeSH terms:
|
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 |
ClinicalTrials.gov processed this record on September 30, 2016