Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments 5-fluorouracil, carboplatin, cyclophosphamide, docetaxel, doxorubicin, epirubicin, paclitaxel, pertuzumab, placebo, trastuzumab
Phase phase 3
Targets HER, HER2
Sponsor Hoffmann-La Roche
Collaborator Genentech, Inc.
Start date November 2011
End date December 2023
Trial size 4806 participants
Trial identifier NCT01358877, 2010-022902-41, BIG 04-11, BO25126, TOC4939G

Summary

This randomized, double-blind, placebo-controlled, two-arm study will assess the safety and efficacy of pertuzumab in addition to chemotherapy plus trastuzumab as adjuvant therapy in participants with operable HER2-positive primary breast cancer. After surgery, participants will be randomized to receive either pertuzumab or placebo intravenously (IV) every 3 weeks (q3w) for one year, along with 6-8 cycles of chemotherapy and 1 year of trastuzumab IV every 3 weeks. This study will be carried out in collaboration with the Breast International Group (BIG).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Participants will receive pertuzumab IV and trastuzumab IV q3w for 1 year of treatment in combination with chemotherapy according to one of the following schedules (as per Investigator's discretion): 1) 3-4 cycles (q3w) of 5-fluorouracil + epirubicin or doxorubicin + cyclophosphamide followed by either 4 cycles (q3w) of docetaxel or 12 weekly cycles of paclitaxel. 2) 4 cycles (q3w) of doxorubicin or epirubicin + cyclophosphamide followed by either 4 cycles (q3w) of docetaxel or 12 weekly cycles of paclitaxel. 3) (Non-Anthracycline therapy) 6 cycles (q3w) of docetaxel + carboplatin.
5-fluorouracil
Participants may receive 5-fluorouracil 500-600 milligrams per square meter (mg/m^2) IV q3w.
carboplatin
Participants may receive carboplatin dose of 6 times Area Under the Concentration Time Curve (AUC) (maximum dose of 900 mg) IV q3w.
cyclophosphamide
Participants may receive cyclophosphamide 500-600 mg/m^2 IV q3w.
docetaxel
Participants may receive docetaxel either 75 mg/m^2 IV q3w, or 100 mg/m^2 IV q3w, or 75 mg/m^2 IV q3w for first cycle followed by 100 mg/m^2 IV q3w.
doxorubicin
Participants may receive doxorubicin 50 mg/m^2 IV q3w.
epirubicin
Participants may receive epirubicin 90-120 mg/m^2 IV q3w.
paclitaxel
Participants may receive paclitaxel 80 mg/m^2 IV once weekly.
pertuzumab
Participants will receive pertuzumab loading dose of 840 mg IV in Cycle 1, followed by 420 mg IV q3w.
trastuzumab Herceptin
Participants will receive trastuzumab at a loading dose of 8 milligrams per kilogram (mg/kg) followed by 6 mg/kg IV q3w.
(Placebo Comparator)
Participants will receive placebo IV and trastuzumab IV q3w for 1 year of treatment in combination with chemotherapy according to one of the following schedules (as per Investigator's discretion): 1) 3-4 cycles (q3w) of 5-fluorouracil + epirubicin or doxorubicin + cyclophosphamide followed by either 4 cycles (q3w) of docetaxel or 12 weekly cycles of paclitaxel. 2) 4 cycles (q3w) of doxorubicin or epirubicin + cyclophosphamide followed by either 4 cycles (q3w) of docetaxel or 12 weekly cycles of paclitaxel. 3) (Non-Anthracycline therapy) 6 cycles (q3w) of docetaxel + carboplatin.
5-fluorouracil
Participants may receive 5-fluorouracil 500-600 milligrams per square meter (mg/m^2) IV q3w.
carboplatin
Participants may receive carboplatin dose of 6 times Area Under the Concentration Time Curve (AUC) (maximum dose of 900 mg) IV q3w.
cyclophosphamide
Participants may receive cyclophosphamide 500-600 mg/m^2 IV q3w.
docetaxel
Participants may receive docetaxel either 75 mg/m^2 IV q3w, or 100 mg/m^2 IV q3w, or 75 mg/m^2 IV q3w for first cycle followed by 100 mg/m^2 IV q3w.
doxorubicin
Participants may receive doxorubicin 50 mg/m^2 IV q3w.
epirubicin
Participants may receive epirubicin 90-120 mg/m^2 IV q3w.
paclitaxel
Participants may receive paclitaxel 80 mg/m^2 IV once weekly.
placebo
Participants will receive pertuzumab matching placebo IV q3w.
trastuzumab Herceptin
Participants will receive trastuzumab at a loading dose of 8 milligrams per kilogram (mg/kg) followed by 6 mg/kg IV q3w.

Primary Outcomes

Measure
Invasive Disease-Free Survival (IDFS) Duration (Excluding Second Primary Non-Breast Cancers as IDFS Event), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
time frame: Randomization until protocol defined IDFS event (excluding second primary non-breast cancers) (up to 12 years overall)
Percentage of Participants with Both a Heart Failure of New York Heart Association (NYHA) Class III or IV and a Drop in Left Ventricular Ejection Fraction (LVEF) of at least 10 Points from Baseline and to Below 50 Percent (%)
time frame: Baseline up to 12 years (assessed every 12 weeks up to first 12 months; months 18, 24, 30, 36, 48, 60 and every 12 months thereafter up to 12 years overall)

Secondary Outcomes

Measure
IDFS Duration (Including Second Primary Non-Breast Cancers as IDFS Event), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
time frame: Randomization until protocol defined IDFS event (including second primary non-breast cancers) (up to 12 years overall)
Disease-Free Survival (DFS) Duration (Including Second Primary Non-Breast Cancers or Contralateral or Ipsilateral Ductal Carcinoma in-Situ as an Event), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
time frame: Randomization until protocol defined DFS event (including second primary non-breast cancers or contralateral or ipsilateral ductal carcinoma in-situ) (up to 12 years overall)
Overall Survival (OS)
time frame: Randomization until death due to any cause (up to 12 years overall)
Recurrence-Free Interval (RFI), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
time frame: Randomization until local, regional or distant breast cancer recurrence (up to 12 years overall)
Distant Recurrence-Free Interval (DRFI), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
time frame: Randomization until distant breast cancer recurrence (up to 12 years overall)
Percentage of Participants with Adverse Events
time frame: Baseline up to 12 years
Percentage of Participants with Asymptomatic or Mildly Symptomatic (NYHA Class II) Drop in Left Ventricular Ejection Fraction (LVEF) of at least 10 Points from Baseline and to Below 50%
time frame: Baseline up to 12 years (assessed every 12 weeks up to first 12 months; months 18, 24, 30, 36, 48, 60 and every 12 months thereafter up to 12 years overall)
LVEF Measurements Over the Course of the Study
time frame: Baseline up to 12 years (assessed every 12 weeks up to first 12 months; months 18, 24, 30, 36, 48, 60 and every 12 months thereafter up to 12 years overall)
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Score
time frame: Baseline, Weeks 10, 13, 19, and 25; 28-days after last dose of study medication (Week 56); and Months 18, 24, and 36
European Organisation for Research and Treatment of Cancer Breast Cancer Module Quality of Life (EORTC QLQ BR23) Functional Scale Score
time frame: Baseline, Weeks 10, 13, 19, and 25; 28-days after last dose of study medication (Week 56); and Months 18, 24, and 36
European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Score
time frame: Baseline, Weeks 10, 13, 19, and 25; 28-days after last dose of study medication (Week 56); and Months 18, 24, and 36

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Non-metastatic operable primary invasive HER2-positive carcinoma of the breast that is histologically confirmed, and adequately excised - Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (/=) 55 percent (%) measured by echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan - Confirmed HER2 positive status - Women of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception (as defined by the protocol) by the participant and/or partner for the duration of the study treatment and for at least 7 months after the last dose of study drug Exclusion Criteria: - History of any prior (ipsi- and/or contralateral) invasive breast cancer - History of non-breast malignancies within the 5 years prior to study entry, except for carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin - Any "clinical" T4 tumor as defined by Primary tumor/regional lymph nodes/distant metastasis (TNM), including inflammatory breast cancer - Any previous systemic chemotherapy for cancer or radiotherapy for cancer - Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy for cancer - Concurrent anti-cancer treatment in another investigational trial - Serious cardiac or cardiovascular disease or condition - Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness - Abnormal laboratory tests immediately prior to randomization - Pregnant or lactating women - Sensitivity to any of the study medications or any of the ingredients or excipients of these medications

Additional Information

Official title A Randomized Multicenter, Double-Blind, Placebo-Controlled Comparison of Chemotherapy Plus Trastuzumab Plus Placebo Versus Chemotherapy Plus Trastuzumab Plus Pertuzumab as Adjuvant Therapy in Patients With Operable HER2-Positive Primary Breast Cancer
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.