A Study to Evaluate Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated Her2-Positive Metastatic Breast Cancer
- Conditions
- HER2 positive metastatic breast cancerMedDRA version: 17.0Level: PTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2007-002997-72-GB
- Lead Sponsor
- F. Hoffmann-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 808
Disease specific inclusion criteria:
1. Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and candidate for chemotherapy. Patients with measurable and/or non-measurable disease are eligible.
Patients with only bone metastases are eligible provided that they have some bone metastases that have not been previously irradiated and tumor tissue samples from the primary tumor are available for central HER 2 testing and subsequent biomarkers analysis.
Locally recurrent disease must not be amenable to resection with curative intent.
Note: Patients with de novo Stage IV disease are eligible.
2. HER2-positive (defined as 3+ IHC or FISH amplification ratio = 2.0 ) MBC confirmed by a Sponsor-designated central laboratory. It is recommended that a formalin-fixed paraffin-embedded (FFPE) tissue block from the primary tumor (or metastatic if the primary is not available) be submitted for central laboratory confirmation of HER2 eligibility; however, if that is not possible, 25 unstained and freshly cut slides will be submitted. (Tissue will subsequently be used for assessment of biomarkers.)
General inclusion criteria:
3. Age = 18 years
4. Left Ventricular Ejection Fraction (LVEF) >= 50% at baseline (within 42 days of randomization) as determined by either ECHO or MUGA (ECHO is the preferred method. If the patient is randomized, the same method of LVEF assessment, ECHO or MUGA, must be used throughout the study, and to the extent possible, be obtained at the same institution) (see Section 7.4.2 of the protocol). All pre-study LVEF values during and post-trastuzumab adjuvant treatment for patients who received such adjuvant therapy prior to enrollment into the study will be collected.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
6. For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly-effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the patient and/or partner. Contraception use must continue for the duration of study treatment and for at least 7 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the pregnancy. For further details see Section 7.2.6.
7. Signed, written informed consent (approved by the Institutional Review Board or Independent Ethics Committee) obtained prior to any study procedure.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 681
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 127
Cancer Related Exclusion Criteria:
1. History of anticancer therapy for MBC (with the exception of one prior hormonal regimen for MBC which must be stopped prior to randomization). Anticancer therapy for MBC includes any EGFR or anti-HER2 agents or vaccines, cytotoxic chemotherapy, or more than one prior hormonal regimen for MBC. One prior hormonal regimen” for MBC may include more than one hormonal therapy, for example, if the switch is not related to disease progression, such as toxicity or local standard practice, this will be counted as one regimen”. If a patient receives hormonal therapy for MBC and is switched to a different hormonal therapy due to disease progression, this will be counted as two regimens” and the patient is not eligible.
2. 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
3. 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
4. History of persistent Grade = 2 hematologic toxicity resulting from previous adjuvant therapy
5. Current peripheral neuropathy of NCI-CTCAE, Version 3.0, Grade = 3 at randomization
6. History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent.
7. Current clinical or radiographic evidence of central nervous system (CNS) metastases. CT or MRI scan of the brain is mandatory (within 28 days of randomization) in cases of clinical suspicion of brain metastases.
8. History of exposure to the following cumulative doses of anthracyclines:
•doxorubicin or liposomal doxorubicin > 360 mg/m2
•epirubicin > 720 mg/m2
•mitoxantrone > 120 mg/m2 and idarubicin > 90 mg/m2
•Other (e.g., liposomal doxorubicin or other anthracycline > the equivalent of 360 mg/m2 of doxorubicin)
•If more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin.
Hematological, Biochemical, and Organ Function
9. Current uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) or unstable angina
10. History of CHF of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia)
11. History of myocardial infarction within 6 months of randomization
12. History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
13. Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
General Exclusion Criteria
14. Inadequate organ function, evidenced by the following laboratory results within 28 days prior to randomization:
•Absolute neutrophil count < 1,500 cells/mm3
•Platelet count < 100,000 cells/mm3
•Hemoglobin < 9 g/dL
•Total bilirubin > upper limit of normal (ULN) (unless the patient has documented Gilbert’s syndrome)
•SGOT (AST) and SGPT (ALT) > 2.5 x ULN
•SGOT (AST) or SGPT (ALT) > 1.5 x ULN with concurrent serum alkaline phosphatase > 2.5 x ULN Serum alkaline phosphatase may be > 2.5 × ULN only if bone metastases are present and AST (SGOT) and ALT (S
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method