Recruitment status:
Recruiting
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known whether giving cyclophosphamide together with doxorubicin is more effective than giving paclitaxel alone in treating breast cancer. PURPOSE: This randomized phase III trial is studying cyclophosphamide and doxorubicin to see how well they work compared to paclitaxel in treating women with invasive breast cancer.
Background information
Other unique IDs:
CDR0000069444
CALGB-40101
Official title:
Cyclophosphamide And Doxorubicin (CA) (4 VS 6 Cycles) Versus Paclitaxel (4 VS 6 Cycles) As Adjuvant Therapy For Breast Cancer in Women With 0-3 Positive Axillary Lymph Nodes:A 2X2 Factorial Phase III Randomized Study
Detailed description:
OBJECTIVES: Primary
Compare the disease-free survival of women with operable breast cancer and 0-3 positive axillary lymph nodes treated with two different schedules (4 vs 6 courses) of adjuvant cyclophosphamide and doxorubicin vs paclitaxel. (Arms II and IV closed to accrual as of 1/30/2008)
Compare the disease-free survival of patients treated with these regimens.
Secondary
Compare overall survival, local control, and time to distant metastasis in patients treated with these regimens.
Compare the toxic effects of these regimens in these patients.
Compare the effect of these regimens on the induction of menopause in premenopausal patients.
Determine the discrepancy of myelosuppression in patients with MDR1 haplotypes on the CA treatment arm.
Compare the disease-free survival of patients with MDR1 haplotypes treated with these regimens.
Correlate CYP3A5, CYP2C8, and CYP2B6 polymorphisms with disease-free survival and toxicity in patients treated with these regimens.
OUTLINE: This is a randomized study. Patients are stratified according to menopausal status (premenopausal vs postmenopausal), estrogen receptor (ER)/progesterone receptor (PR) status (ER and/or PR positive or unknown vs ER and PR negative), and HER2/neu status (negative vs unknown vs positive [by immunohistochemistry 3+ staining or gene amplification by fluorescence in situ hybridization]). Patients are randomized to 1 of 4 treatment arms (arms II and IV closed to accrual as of 1/30/2008).
Arm I: Patients receive doxorubicin IV and cyclophosphamide IV on day 1. Treatment repeats every 14 days for 4 courses.
Arm II (closed to accrual as of 1/30/2008): Patients receive doxorubicin and cyclophosphamide as in arm I. Treatment repeats every 14 days for 6 courses.
Arm III: Patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 14 days for 4 courses.
Arm IV (closed to accrual as of 1/30/2008): Patients receive paclitaxel as in arm III. Treatment repeats every 14 days for 6 courses.
Treatment in all arms continues in the absence of disease progression or unacceptable toxicity. Lumpectomy patients must then undergo radiotherapy. Mastectomy patients undergo radiotherapy at the discretion of the treating physician. Patients are followed every 6 months for 2 years and then annually for 15 years. PROJECTED ACCRUAL: A total of 4,646 patients will be accrued for this study within 29 months.
Clinical information
Eligibility criteria:
DISEASE CHARACTERISTICS:
Histologically confirmed invasive carcinoma of the breast with 0-3 positive axillary lymph nodes
Meets 1 of the following criteria for node-negative disease:
Negative sentinel lymph node biopsy
At least 6 negative axillary lymph nodes removed and determined to be negative by axillary dissection
Meets 1 of the following criteria for node-positive disease (1-3 positive axillary lymph nodes):
At least 1 positive lymph node by sentinel lymph node biopsy AND at least 6 axillary lymph nodes removed by axillary dissection; of all the nodes removed from both the sentinel lymph node biopsy and the axillary dissection, 1-3 must be positive
At least 6 lymph nodes removed by axillary dissection; 1-3 nodes from the axillary dissection must be positive
"High-risk" disease that warrants chemotherapy (ultimately determined by the treating physician)
Modified radical mastectomy or lumpectomy within the past 84 days required
Negative tumor margins for invasive cancer and ductal carcinoma in situ (DCIS)
Lobular carcinoma in situ (LCIS) at the margin allowed
Multicentric disease allowed provided margins and axillary nodes are negative after resection
Bilateral synchronous disease allowed
Invasive cancer on one side and DCIS or LCIS on the contralateral side is allowed provided all other eligibility criteria are met
No locally advanced, inflammatory, or metastatic breast cancer
No dermal lymphatics involvement, even if there are no clinical signs of inflammatory cancer
HER2/neu positive, negative, or unknown
Hormone receptor status:
Any estrogen and/or progesterone receptor status
PATIENT CHARACTERISTICS: Age:
Sex:
Menopausal status:
Premenopausal or postmenopausal
Performance status:
Life expectancy:
Hematopoietic:
Absolute neutrophil count at least 1,000/mm^3
Platelet count at least 100,000/mm^3
Hepatic:
Bilirubin no greater than 1.5 times upper limit of normal
Renal:
Creatinine no greater than 2.0 mg/dL
Cardiovascular:
No active congestive heart failure
No myocardial infarction within the past 6 months
Other:
Not pregnant or nursing
Fertile patients must use effective nonhormonal contraception during and for at least 2 months after study participation
No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY: Biologic therapy:
No prior trastuzumab (Herceptin^®) for this malignancy
Chemotherapy:
See Disease Characteristics
No prior chemotherapy for this malignancy
No other concurrent chemotherapy
Endocrine therapy:
No prior hormonal therapy for this malignancy except tamoxifen given for up to 4 weeks
Prior tamoxifen or other selective estrogen receptor modulators (SERMs) for prevention or other indications (e.g., osteoporosis) allowed
No concurrent exogenous hormonal therapy (including oral contraceptives, postmenopausal hormone replacement therapy, or raloxifene) except:
Steroids for adrenal failure
Hormonal agents for nondisease-related conditions (e.g., insulin for diabetes or synthroid for hypothyroidism)
Intermittent dexamethasone as an antiemetic and premedication for paclitaxel
No concurrent tamoxifen or other SERMs
Surgery:
See Disease Characteristics
Other:
No concurrent dexrazoxane
No concurrent raloxifene
Concurrent bisphosphonates for osteoporosis allowed
Concurrent trastuzumab (Herceptin^®) allowed for patients with HER2-positive disease
Concurrent enrollment on adjuvant bisphosphonate studies allowed
Concurrent enrollment on adjuvant hormonal studies allowed provided hormonal therapy does not commence until completion of study chemotherapy
Study design:
Treatment
Randomized
Active Control
Interventions:
cyclophosphamide
doxorubicin hydrochloride
paclitaxel
Study arms:
Active Comparator: Patients receive doxorubicin IV and cyclophosphamide IV on day 1. Treatment repeats every 14 days for 4 courses.
Experimental: Patients receive doxorubicin and cyclophosphamide as in arm I. Treatment repeats every 14 days for 6 courses.
Experimental: Patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 14 days for 4 courses.
Experimental: Patients receive paclitaxel as in arm III. Treatment repeats every 14 days for 6 courses.
Outcome measurements:
Toxicity [ Designated as safety issue: Yes ]
Overall survival [ Designated as safety issue: No ]
Myelosuppression in patients with MDR1 haplotypes [ Designated as safety issue: No ]
CYP3A5, CYP2C8, and CYP2B6 polymorphisms [ Designated as safety issue: No ]
Funding
Dates
Date the data was first received:
