Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting
Trial record 1 of 1 for:    NCT01358877
Previous Study | Return to List | Next Study

A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Genentech, Inc.
Breast International Group
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01358877
First received: May 20, 2011
Last updated: September 1, 2016
Last verified: August 2016
  Purpose
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).

Condition Intervention Phase
Breast Cancer
Drug: 5-Fluorouracil
Drug: Carboplatin
Drug: Cyclophosphamide
Drug: Docetaxel
Drug: Doxorubicin
Drug: Epirubicin
Drug: Paclitaxel
Drug: Pertuzumab
Drug: Placebo
Drug: Trastuzumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Randomization until death due to any cause (up to 12 years overall) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline up to 12 years ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 4806
Study Start Date: November 2011
Estimated Study Completion Date: December 2023
Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pertuzumab + Trastuzumab + Chemotherapy
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.
Drug: 5-Fluorouracil
Participants may receive 5-fluorouracil 500-600 milligrams per square meter (mg/m^2) IV q3w.
Drug: Carboplatin
Participants may receive carboplatin dose of 6 times Area Under the Concentration Time Curve (AUC) (maximum dose of 900 mg) IV q3w.
Drug: Cyclophosphamide
Participants may receive cyclophosphamide 500-600 mg/m^2 IV q3w.
Drug: 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.
Drug: Doxorubicin
Participants may receive doxorubicin 50 mg/m^2 IV q3w.
Drug: Epirubicin
Participants may receive epirubicin 90-120 mg/m^2 IV q3w.
Drug: Paclitaxel
Participants may receive paclitaxel 80 mg/m^2 IV once weekly.
Drug: Pertuzumab
Participants will receive pertuzumab loading dose of 840 mg IV in Cycle 1, followed by 420 mg IV q3w.
Drug: Trastuzumab
Participants will receive trastuzumab at a loading dose of 8 milligrams per kilogram (mg/kg) followed by 6 mg/kg IV q3w.
Other Name: Herceptin
Placebo Comparator: Placebo + Trastuzumab + Chemotherapy
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.
Drug: 5-Fluorouracil
Participants may receive 5-fluorouracil 500-600 milligrams per square meter (mg/m^2) IV q3w.
Drug: Carboplatin
Participants may receive carboplatin dose of 6 times Area Under the Concentration Time Curve (AUC) (maximum dose of 900 mg) IV q3w.
Drug: Cyclophosphamide
Participants may receive cyclophosphamide 500-600 mg/m^2 IV q3w.
Drug: 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.
Drug: Doxorubicin
Participants may receive doxorubicin 50 mg/m^2 IV q3w.
Drug: Epirubicin
Participants may receive epirubicin 90-120 mg/m^2 IV q3w.
Drug: Paclitaxel
Participants may receive paclitaxel 80 mg/m^2 IV once weekly.
Drug: Placebo
Participants will receive pertuzumab matching placebo IV q3w.
Drug: Trastuzumab
Participants will receive trastuzumab at a loading dose of 8 milligrams per kilogram (mg/kg) followed by 6 mg/kg IV q3w.
Other Name: Herceptin

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 (</=) 1
  • The interval between definitive surgery for breast cancer and the first dose of chemotherapy must be no more than 8 weeks (56 days). The first cycle of chemotherapy must be administered within 7 days of randomization or on Day 56, whichever occurs first
  • Known hormone receptor status (estrogen receptor and progesterone receptor)
  • Baseline LVEF greater 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01358877

  Show 591 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Genentech, Inc.
Breast International Group
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01358877     History of Changes
Other Study ID Numbers: BO25126  TOC4939G  2010-022902-41  BIG 04-11 
Study First Received: May 20, 2011
Last Updated: September 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Docetaxel
Liposomal doxorubicin
Pertuzumab
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Doxorubicin
Trastuzumab
Epirubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on September 30, 2016