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| Sponsor: | National Surgical Adjuvant Breast and Bowel Project (NSABP) |
|---|---|
| Collaborators: |
Cancer International Research Group Hoffmann-La Roche Genentech |
| Information provided by: | National Surgical Adjuvant Breast and Bowel Project (NSABP) |
| ClinicalTrials.gov Identifier: | NCT00625898 |
Purpose
The trial will determine the value of adding bevacizumab to chemotherapy plus trastuzumab in patients with resected node-positive or high risk node-negative, HER2-positive breast cancer.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer |
Drug: Docetaxel Drug: Trastuzumab Drug: Carboplatin Drug: Bevacizumab Drug: 5-Fluorouracil Drug: Epirubicin Drug: Cyclophosphamide |
Phase III |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study |
| Official Title: | A Multicenter Phase III Randomized Trial of Adjuvant Therapy for Patients With HER2-Positive Node-Positive or High Risk Node-Negative Breast Cancer Comparing Chemotherapy Plus Trastuzumab With Chemotherapy Plus Trastuzumab Plus Bevacizumab |
| Estimated Enrollment: | 3500 |
| Study Start Date: | April 2008 |
| Estimated Study Completion Date: | June 2021 |
| Estimated Primary Completion Date: | August 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
1A: TCH-H: Active Comparator
Docetaxel (T), Carboplatin (C), and Trastuzumab (H) followed by Trastuzumab (H)
|
Drug: Docetaxel
75 mg/m2 IV on day 1 every 3 weeks for cycles 1-6, Arms 1A and 1B 100 mg/m2 on day 1 every 3 weeks for cycles 1-3, Arms 2A and 2B First dose: 8 mg/kg IV on day 1 of cycle 1 only. Subsequent doses: 6 mg/kg IV on day 1 every 3 weeks for cycles 2-6. Following completion of chemotherapy cycles: 6 mg/kg IV every 3 weeks until 1 year following first trastuzumab dose. Arms 1A and 1B First dose: 8 mg/kg IV on day 1 of cycle 1 only. Subsequent doses: 6 mg/kg IV on day 1 every 3 weeks for cycles 2-3. 21 days after last dose of FEC: 8 mg/kg IV first post-FEC dose only; subsequent doses 6 mg/kg IV every 3 weeks for a total of 1 year. Arms 2A and 2B
6 mg/ml/min IV on day 1 every 3 weeks for cycles 1-6
|
|
1B: TCHB-HB: Experimental
Docetaxel (T), Carboplatin (C), Trastuzumab (H), Bevacizumab (B) followed by Trastuzumab (T) and Bevacizumab (B)
|
Drug: Docetaxel
75 mg/m2 IV on day 1 every 3 weeks for cycles 1-6, Arms 1A and 1B 100 mg/m2 on day 1 every 3 weeks for cycles 1-3, Arms 2A and 2B First dose: 8 mg/kg IV on day 1 of cycle 1 only. Subsequent doses: 6 mg/kg IV on day 1 every 3 weeks for cycles 2-6. Following completion of chemotherapy cycles: 6 mg/kg IV every 3 weeks until 1 year following first trastuzumab dose. Arms 1A and 1B First dose: 8 mg/kg IV on day 1 of cycle 1 only. Subsequent doses: 6 mg/kg IV on day 1 every 3 weeks for cycles 2-3. 21 days after last dose of FEC: 8 mg/kg IV first post-FEC dose only; subsequent doses 6 mg/kg IV every 3 weeks for a total of 1 year. Arms 2A and 2B
6 mg/ml/min IV on day 1 every 3 weeks for cycles 1-6
Drug: Bevacizumab
15 mg/kg IV on day 1 every 3 weeks for cycles 1-6. Following completion of chemotherapy cycles: 15 mg/kg IV on day 1 every 3 weeks until 1 year following first bevacizumab dose. Arm 1B 15 mg/kg IV on day 1 every 3 weeks for cycles 1-3. 21 days after the last dose of FEC: 15 mg/kg IV on day 1 every 3 weeks until 1 year following first bevacizumab dose. Arm 2B |
|
2A: TH-FEC-H: Active Comparator
Docetaxel (T) and Trastuzumab (H) followed by 5-fluorouracil (F), Epirubicin (E), and Cyclophosphamide (C) followed by Trastuzumab (H)
|
Drug: Docetaxel
75 mg/m2 IV on day 1 every 3 weeks for cycles 1-6, Arms 1A and 1B 100 mg/m2 on day 1 every 3 weeks for cycles 1-3, Arms 2A and 2B First dose: 8 mg/kg IV on day 1 of cycle 1 only. Subsequent doses: 6 mg/kg IV on day 1 every 3 weeks for cycles 2-6. Following completion of chemotherapy cycles: 6 mg/kg IV every 3 weeks until 1 year following first trastuzumab dose. Arms 1A and 1B First dose: 8 mg/kg IV on day 1 of cycle 1 only. Subsequent doses: 6 mg/kg IV on day 1 every 3 weeks for cycles 2-3. 21 days after last dose of FEC: 8 mg/kg IV first post-FEC dose only; subsequent doses 6 mg/kg IV every 3 weeks for a total of 1 year. Arms 2A and 2B
600 mg/m2 IV on day 1 every 3 weeks for cycles 4-6
Drug: Epirubicin
90 mg/m2 IV on day 1 every 3 weeks for cycles 4-6
Drug: Cyclophosphamide
600 mg/m2 IV on day 1 every 3 weeks for cycles 4-6
|
|
2B: THB-FEC-HB: Experimental
Docetaxel (T), Trastuzumab (H), and Bevacizumab (B) followed by 5-Fluorouracil (F), Epirubicin (E), and Cyclophosphamide (C) followed by Trastuzumab (H) and Bevacizumab (B)
|
Drug: Docetaxel
75 mg/m2 IV on day 1 every 3 weeks for cycles 1-6, Arms 1A and 1B 100 mg/m2 on day 1 every 3 weeks for cycles 1-3, Arms 2A and 2B First dose: 8 mg/kg IV on day 1 of cycle 1 only. Subsequent doses: 6 mg/kg IV on day 1 every 3 weeks for cycles 2-6. Following completion of chemotherapy cycles: 6 mg/kg IV every 3 weeks until 1 year following first trastuzumab dose. Arms 1A and 1B First dose: 8 mg/kg IV on day 1 of cycle 1 only. Subsequent doses: 6 mg/kg IV on day 1 every 3 weeks for cycles 2-3. 21 days after last dose of FEC: 8 mg/kg IV first post-FEC dose only; subsequent doses 6 mg/kg IV every 3 weeks for a total of 1 year. Arms 2A and 2B 15 mg/kg IV on day 1 every 3 weeks for cycles 1-6. Following completion of chemotherapy cycles: 15 mg/kg IV on day 1 every 3 weeks until 1 year following first bevacizumab dose. Arm 1B 15 mg/kg IV on day 1 every 3 weeks for cycles 1-3. 21 days after the last dose of FEC: 15 mg/kg IV on day 1 every 3 weeks until 1 year following first bevacizumab dose. Arm 2B
600 mg/m2 IV on day 1 every 3 weeks for cycles 4-6
Drug: Epirubicin
90 mg/m2 IV on day 1 every 3 weeks for cycles 4-6
Drug: Cyclophosphamide
600 mg/m2 IV on day 1 every 3 weeks for cycles 4-6
|
This Phase III, randomized, open-label trial will determine whether the regimens of chemotherapy plus trastuzumab plus bevacizumab improve invasive disease-free survival (IDFS) relative to the regimens of chemotherapy plus trastuzumab. Secondary aims include determining whether the addition of bevacizumab to chemotherapy plus trastuzumab will improve disease-free survival (DFS), overall survival (OS), recurrence-free interval (RFI), and distant recurrence-free interval (DRFI). The benefit of adding bevacizumab for IDFS, DFS, OS, RFI, and DRFI will also be evaluated for each of the two chemotherapy regimens. The cardiac and non-cardiac toxicities of each of the regimens will also be evaluated.
Following local determination that the tumor is HER2-positive for gene amplification by in situ hybridization or is IHC 2+ or 3+, a tumor sample must be submitted for HER2 testing by a designated central laboratory. If central testing confirms that the tumor is HER2-positive (either positive by FISH or IHC 3+) and all other eligibility criteria have been met, the patient will be randomized to a regimen of chemotherapy and trastuzumab with or without bevacizumab.
Patients in the trial will be enrolled in one of two chemotherapy regimen cohorts. One cohort will receive 6 cycles of docetaxel/carboplatin plus trastuzumab (TCH) with or without bevacizumab; the other cohort will receive 3 cycles of docetaxel plus trastuzumab given with or without bevacizumab followed by 3 cycles of 5-Fluorouracil, Epirubicin, Cyclophosphamide (TH-FEC). With both regimens, patients will continue trastuzumab with or without bevacizumab following chemotherapy to complete 1 year of targeted therapy. Following completion of chemotherapy, patients will also receive adjuvant radiotherapy and endocrine therapy as clinically indicated.
The trial will be conducted by investigators affiliated with the Cancer International Research Group (CIRG) and the National Surgical Adjuvant Breast and Bowel Project (NSABP). CIRG and NSABP investigators will only enroll patients in the TCH regimen cohort. Additional investigators, referred to in the protocol as Independent Investigators, will enroll patients in both the TCH regimen or the TH-FEC regimen cohort depending on institutional preference for the one regimen that will be used by that institution for the duration of the trial.
Patients will be given the option of allowing their tumor samples to be used for the BETH translational research and correlative science studies. Also, patients will be asked to consent to the submission of blood and serum samples at scheduled time points during the study.
LVEF assessments will be performed before study entry and then at scheduled time points during therapy and at 18, 36, and 60 months following randomization.
The planned sample size for the trial is 3,000 patients randomized in the faster accruing cohort and a minimum of 3,500 patients overall.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| Contact: Diana Gosik, RN, BS | 412-330-4692 | diana.gosik@nsabp.org |
Show 597 Study Locations| Principal Investigator: | Norman Wolmark, MD | NSABP Foundation, Inc. |
More Information
| Responsible Party: | NSABP Foundation, Inc. ( Norman Wolmark, MD ) |
| Study ID Numbers: | NSABP B-44-I, CIRG (TRIO) 011, Roche BO20906, BETH |
| Study First Received: | February 21, 2008 |
| Last Updated: | January 28, 2010 |
| ClinicalTrials.gov Identifier: | NCT00625898 History of Changes |
| Health Authority: | United States: Food and Drug Administration; Canada: Health Canada; Canada: Ethics Review Committee |
|
HER2 positive breast cancer invasive breast cancer bevacizumab NSABP Roche CIRG |
trastuzumab cyclophosphamide docetaxel carboplatin 5-fluorouracil epirubicin |
|
Antimetabolites Antimetabolites, Antineoplastic Immunologic Factors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Physiological Effects of Drugs Bevacizumab Cyclophosphamide Antibiotics, Antineoplastic Docetaxel Neoplasms by Site Therapeutic Uses Trastuzumab Growth Inhibitors Angiogenesis Modulating Agents |
Alkylating Agents Breast Diseases Skin Diseases Growth Substances Breast Neoplasms Carboplatin Angiogenesis Inhibitors Immunosuppressive Agents Epirubicin Pharmacologic Actions Neoplasms Fluorouracil Myeloablative Agonists Antineoplastic Agents, Alkylating Antirheumatic Agents |