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

Phase 1

• Conditions: HER2 positive metastatic breast cancer; MedDRA version: 9.1Level: LLTClassification code 10006202Term: Breast cancer stage IV; MedDRA version: 9.1Level: LLTClassification code 10065430Term: HER-2 positive breast cancer; MedDRA version: 9.1Level: LLTClassification code 10021974Term: Inflammatory breast cancer

• Registration Number: EUCTR2007-002997-72-FR
• Lead Sponsor: F. Hoffmann-La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-01-15
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 808

Inclusion Criteria

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 nonmeasurable lesion are eligible. 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 strongly recommended that a formalin-fixed paraffin-embedded (FFPE) tissue block from the primary tumor 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, page 98). 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, agreement to use an effective form of contraception (patient and/or partner, e.g., surgical sterilization, a reliable barrier method [condoms, diaphragm], intrauterine devices, or abstinence) and to continue its use for the duration of study treatment and for 6 months after the last dose of
study treatment7. 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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Cancer Related Exclusion Criteria:
1. History of anticancer therapy for MBC (with the exception of one prior hormonal regimen for MBC). This includes any EGFR or anti-HER2 agents or vaccines, cytotoxic chemotherapy, or more than one prior hormonal regimen for MBC.
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
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 (unless bone metastases are present)
•Serum creatinine > 2.0 mg/dL or 177 µmol/L
•International normalized ratio (INR) and activated partial thromboplastin time (aPTT) > 1.5 x ULN (unless on therapeutic coagulation)
15. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures)
16. 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
17. Pregnant or lactating women
18. History of receiving any investigational treatment within 28 days of randomization
19. Current kno

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified