Four Versus Six Cycles of Cyclophosphamide/Doxorubicin or Paclitaxel in Adjuvant Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT00041119
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
This randomized phase III trial studies cyclophosphamide and doxorubicin hydrochloride compared with paclitaxel as adjuvant therapy in treating breast cancer in women with 0-3 positive axillary lymph nodes. Giving additional cancer treatment after surgery may help to lower the risk that the cancer will come back (adjuvant therapy). Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether the standard adjuvant therapy of cyclophosphamide and doxorubicin hydrochloride is more effective than paclitaxel in treating women with breast cancer
- Detailed Description
PRIMARY OBJECTIVES:
I. To determine the equivalence of paclitaxel given every two weeks with cyclophosphamide and doxorubicin hydrochloride (CA) given every two weeks as adjuvant therapy for women with 0-3 positive axillary lymph nodes, for disease-free survival.
II. To determine if longer therapy, 12 weeks, is superior to shorter therapy, 8 weeks, of either CA or paclitaxel for disease-free survival for women with primary breast cancer with 0-3 positive axillary lymph nodes.
SECONDARY OBJECTIVES:
I. To determine the equivalence of paclitaxel given every two weeks with CA given every two weeks, and the potential superiority of longer vs. shorter therapy, in relation to overall survival, local control (regardless of metastatic status) and time to distant metastases (regardless of local recurrence status).
II. To compare toxicities of short and long course CA and paclitaxel as adjuvant therapy for women with 0-3 positive axillary lymph node breast cancer.
III. To determine the effect of long and short course CA and paclitaxel on the induction of menopause for pre-menopausal patients.
IV. To assess the discrepancy of myelosuppression among the common multidrug resistance protein 1 (MDR1) haplotypes in the CA treatment arm.
V. To assess the effect of MDR1 haplotypes on disease-free survival (DFS) adjusted for treatment.
VI. Exploratory analysis of the effect of cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A5), cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8), and cytochrome P450, family 2, subfamily B, polypeptide 6 (CYP2B6) polymorphisms on DFS and toxicity.
VII. To identify genetic markers associated with the risk of developing neutropenia in adriamycin/ cyclophosphamide-treated breast cancer patients.
VIII. To identify genetic markers associated with the risk of developing peripheral neuropathy in paclitaxel-treated breast cancer patients.
IX. To identify genetic markers associated with differences in the efficacy of each chemotherapy regimen.
X. To examine genetic associations with other response and toxicity phenotypes that become apparent during future analysis of Cancer and Leukemia Group B (CALGB) 40101 data.
XI. To identify copy number variants associated with adriamycin/cyclophosphamide-induced neutropenia and paclitaxel-induced peripheral neuropathy.
OUTLINE: Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive cyclophosphamide intravenously (IV) and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
ARM III: Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
ARM IV: Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Note: Randomization to Arms II and IV is no longer available, effective 12/15/2007.
After completion of study treatment patients are followed up for 4-6 weeks, every 6 months for 2 years, and then annually for up to 13 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 3871
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Arm I (CA for 4 courses) AC regimen Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Arm I (CA for 4 courses) doxorubicin hydrochloride Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Arm II (CA for 6 courses [closed to accrual 12/15/2007]) doxorubicin hydrochloride Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm III (paclitaxel for 4 courses) AC regimen Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Arm II (CA for 6 courses [closed to accrual 12/15/2007]) AC regimen Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm III (paclitaxel for 4 courses) paclitaxel Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Arm IV (paclitaxel for 6 courses [closed 12/15/2007]) AC regimen Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm IV (paclitaxel for 6 courses [closed 12/15/2007]) paclitaxel Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm II (CA for 6 courses [closed to accrual 12/15/2007]) cyclophosphamide Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Duration of Disease Free Survival (RFS) from baseline up to 6.4 years To determine the equivalence of paclitaxel to CA as adjuvant therapy for women with 0-3 positive axillary lymph nodes, for disease-free survival. Objective progression is defined as the appearance of local (chest wall, axillary, supraclavicular nodes) or distant metastases. The trial is designed to show the equivalence of the experimental agent T with the standard agent combination CA, thus the 4 and 6 course arms of each drug will be combined to conduct this analysis.
Relapse Free Survival (RFS) 4 vs. 6 Cycles from baseline up to 4 years To determine if longer therapy, 12 weeks, is superior to shorter therapy, 8 weeks, of either CA or paclitaxel for relapse-free survival for women with primary breast cancer with 0-3 positive axillary lymph nodes. An assessment of the superiority of 6 cycles over 4 cycles will be conducted. This analysis combines Arm I and Arm III together, and Arm II and Arm IV together.
- Secondary Outcome Measures
Name Time Method Adverse Events from baseline up to 6 weeks post-treatment To compare toxicities of short course CA and paclitaxel with long course CA and paclitaxel as adjuvant therapy for women with 0-3 positive axillary lymph node breast cancer. The percentage of patients that received a grade 3 or higher hematologic event will be reported here. We will be combining arm I with arm III, as well as arm II with arm IV. For a complete list of adverse events, please refer to the adverse events section.
Time to Distant Metastases from baseline up to 15 years Local control and distant metastasis will be calculated as the cumulative incidence of first local relapse and first distant metastasis, respectively.
Overall Survival (OS) for 4 vs. 6 Cycles from baseline up to 4 years To determine if longer therapy, 12 weeks, is superior to shorter therapy, 8 weeks, of either CA or paclitaxel for overall survival for women with primary breast cancer with 0-3 positive axillary lymph nodes. An assessment of the superiority of 6 cycles over 4 cycles will be conducted. This analysis combines Arm I and Arm III together, and Arm II and Arm IV together.
Overall Survival (OS) from baseline up to 5 years To determine the equivalence of paclitaxel to CA as adjuvant therapy for women with 0-3 positive axillary lymph nodes, for overall survival. OS will be measured from study entry until death due to any cause. Survivors will be censored at the date of last follow-up.. The trial is designed to show the equivalence of the experimental agent T with the standard agent combination CA, thus the 4 and 6 course arms of each drug will be combined to conduct this analysis.
Local Control from baseline up to 15 years Local control will be calculated as the cumulative incidence of first local relapse.
Trial Locations
- Locations (522)
Regional Medical Center
🇺🇸Anniston, Alabama, United States
UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Providence Cancer Center at Providence Hospital
🇺🇸Mobile, Alabama, United States
Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital
🇺🇸Fairbanks, Alaska, United States
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
🇺🇸Ft. Smith, Arkansas, United States
Alta Bates Summit Comprehensive Cancer Center
🇺🇸Berkeley, California, United States
Peninsula Medical Center
🇺🇸Burlingame, California, United States
East Bay Radiation Oncology Center
🇺🇸Castro Valley, California, United States
Valley Medical Oncology Consultants - Castro Valley
🇺🇸Castro Valley, California, United States
Scroll for more (512 remaining)Regional Medical Center🇺🇸Anniston, Alabama, United States