HER2- and hormone receptor-positive advanced (metastatic or locally advanced) breast cancer MedDRA version: 14.0 Level: LLT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent approved by the Institutional Ethical Review Board (IRB). 2. Age greater than or equal to 18 years. 3. Postmenopausal status >1 year (fulfilling one or more of National Comprehensive Cancer Network [NCCN] guideline criteria, Version 2.2011). 4. Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection. 5. HER2-positive (defined as either IHC 3+ or ISH positive) as assessed by local laboratory on primary or metastatic tumor (ISH positivity is defined as a ratio of 2.0 or greater for the number of HER2 gene copies to the number of signals for CEP17, or for single probe tests, a HER2 gene count greater than 4). 6. Hormone receptor-positive defined as ER-positive and/or PgR-positive assessed locally as defined by institutional criteria. 7. At least one measurable lesion and/or non-measurable disease evaluable according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (Eisenhauer et al. 2009). 8. ECOG performance status 0 or 1. 9. Left ventricular ejection fraction (LVEF) of at least 50%. 10. Life expectancy of at least 12 weeks. 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 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Previous systemic non-hormonal anticancer therapy in the metastatic or locally advanced breast cancer setting. 2. Disease-free interval from completion of adjuvant or neo-adjuvant systemic non-hormonal treatment to recurrence of within 6 months. 3. Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except trastuzumab and/or lapatinib in the neoadjuvant or adjuvant setting. 4. Disease progression while receiving trastuzumab and/or lapatinib in the adjuvant setting. 5. History of persistent grade 2 or higher (NCI-CTC, Version 4.0) hematological toxicity resulting from previous adjuvant or neo-adjuvant therapy. 6. Radiographic evidence of central nervous system (CNS) metastases as assessed by CT or MRI. 7. Current peripheral neuropathy of grade 3 or higher (NCI-CTC, Version 4.0). 8. History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma. 9. Serious uncontrolled concomitant disease that would contraindicate the use of any of the investigational drugs used in this study or that would put the patient at high risk for reatment related complications. 10. Inadequate organ function, evidenced by the following laboratory results: ? Absolute neutrophil count 2.5 × ULN. ? AST (SGOT) or ALT (SGPT) >1.5 × ULN with concurrent serum alkaline phosphatase >2.5 × ULN Serum alkaline phosphatase may be >2.5 × ULN only if bone metastases are present and AST (SGOT) and ALT (SGPT) 2.0 mg/dL or 177 ?mol/L. ? International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic coagulation). 11. Uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident (CVA)/stroke or myocardial infarction within 6 months prior to first study edication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) grade II or higher, or serious cardiac arrhythmia requiring medication. 12. Current known infection with HIV, HBV, or HCV. 13. Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy. 14. Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of need for major surgery during the course of study treatment. 15. Lack of physical integrity of the upper gastrointestinal tract, clinically significant malabsorption syndrome, or inability to take oral medication. 16. Receipt of intravenous antibiotics for infection within 14 days prior to randomization. 17. Current chronic daily treatment with corticosteroids (dose of 10 mg/day methylprednisolone equivalent), excluding inhaled steroids. 18. Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies. 19. History of receiving any investigational treatment within 28 days prior to randomization. 20. Concurrent participation in any clinical trial. 21. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare progression-free survival (PFS) of pertuzumab given in combination with trastuzumab plus an aromatase inhibitor (AI) versus trastuzumab plus an AI.;Secondary Objective: To compare pertuzumab given in combination with trastuzumab plus an AI versus trastuzumab plus an AI with respect to: ? Overall survival (OS) ? Overall response rate (ORR) ? Clinical benefit rate (CBR) ? Duration of response ? Time to response ? Safety and tolerability ? Quality of life (EQ-5D questionnaires);Primary end point(s): The primary efficacy endpoint is Progression-Free Survival (PFS).;Timepoint(s) of evaluation of this end point: Analysis of PFS will be performed when 165 events have occurred. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are: - OS - ORR - CBR - Duration of response - Time to response;Timepoint(s) of evaluation of this end point: A first analysis of OS will be performed with the final analysis of PFS. The final analysis of OS will take place once all patients have been followed up for at least 24 months after the last patient is randomized, unless they have been lost to follow-up, withdrawn consent, or died, whichever occurs first. All other secondary endpoints will be summarized with the final analysis of PFS. | — |
Countries
Brazil, France, India, Italy, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd.
Outcome results
None listed