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Phase III Randomized Study of Doxorubicin and Cyclophosphamide Followed By Paclitaxel or Docetaxel in Women With Node-Positive or High-Risk Node-Negative Stage II or IIIA Breast Cancer
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outline Published Results Trial Contact Information Registry Information
Alternate Title
Combination Chemotherapy in Treating Women With Stage II or Stage IIIA Breast Cancer That Has Spread to the Lymph Nodes
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
---|
Phase III | Treatment | Completed | 18 and over | E-1199 CLB-49906, NCCTG-E1199, SWOG-E1199, NCT00004125, E1199 |
Objectives - Compare the disease-free survival and overall survival in patients with node-positive or high-risk node-negative operable stage II or IIIA breast cancer treated with docetaxel or paclitaxel after doxorubicin and cyclophosphamide.
- Determine whether the weekly administration of paclitaxel or docetaxel for 12 weeks improves disease-free survival and overall survival when compared with the conventional schedule of every 3 weeks for 4 courses after doxorubicin and cyclophosphamide in this patient population.
- Compare the toxic effects of docetaxel and paclitaxel when administered weekly for 12 weeks versus every 3 weeks for 4 courses in these patients.
- Compare the toxicity of paclitaxel administered every 3 weeks for 4 courses or weekly for 12 weeks to that of docetaxel administered on the same schedules in these patients.
Entry Criteria Disease Characteristics:
- Histologically confirmed operable stage IIA, IIB, or IIIA adenocarcinoma
of
the breast with histologically involved lymph nodes (T1, 2, or 3; N1 or
2; M0) OR high-risk node-negative disease (T2 or 3; N0)
- Primary tumor at least 2.1 cm in diameter for
node-negative disease
- Bilateral breast disease allowed if at least 1 primary
tumor meets the
criteria above
- Must have had at least 6 axillary lymph nodes removed at dissection and
at
least one node positive for metastasis
OR
- Sentinel node biopsy negative for metastasis (sentinel node biopsy
positive
allowed if enrolled on American College of Surgery Trial Z0011 and have
beenrandomized to receive no axillary dissection)
- Additional axillary nodes may be obtained provided
they are also negative for
metastasis
- Complete tumor removal by either a modified radical mastectomy or local
excision plus axillary lymph node dissection (i.e., breast conservation
therapy) or sentinel node biopsy
- Tumor-free margins at least 1 mm for both invasive
and noninvasive
carcinoma except for lobular carcinoma in situ (less
than 1 mm allowed)
- Concurrent enrollment on American College of Surgery Trial Z0010, Z0011,
or
NSABP B-32 allowed
- Hormone receptor status:
-
Estrogen receptor status positive, negative, or
unknown
Prior/Concurrent Therapy:
Biologic therapy: Chemotherapy: - No prior chemotherapy for breast cancer
Endocrine therapy: - Prior tamoxifen of no more than 4 weeks duration for breast
cancer allowed
- Prior tamoxifen or other selective estrogen receptor modulator
(SERM) for chemoprevention (e.g., Breast Cancer Prevention Trial) or for
other indications (e.g., osteoporosis) allowed
- No concurrent tamoxifen or other SERMs
Radiotherapy: - No prior radiotherapy for this malignancy
- At least 2 weeks since prior radiotherapy to the breast for
ductal carcinoma in situ
Surgery: - See Disease Characteristics
- Less than 84 days since prior surgical procedure to adequately
treat primary tumor
Patient Characteristics:
Age: Sex: Menopausal status: Performance status: Life expectancy: Hematopoietic: - Neutrophil count at least 1,500/mm3
- Platelet count at least 100,000/mm3
Hepatic: - Bilirubin no greater than 1.5 mg/dL
- SGOT no greater than 2 times upper limit of normal
Renal: - Creatinine no greater than 1.5 mg/dL
Cardiovascular: - No history of myocardial infarction
- No congestive heart failure
- No significant ischemic or valvular heart disease
Other: - No other prior invasive malignancies within the past 5 years
except curatively treated basal or squamous cell skin cancer or
carcinoma in situ of the cervix
- No hypersensitivity to paclitaxel or docetaxel or other
similarly formulated drugs (with Cremophor or polysorbate)
- Not pregnant or nursing
- Fertile patients must use effective barrier
contraception
Expected Enrollment A total of 5,000 patients will be accrued for this study within 1.27 years. Outline This is a randomized, multicenter study. Patients are stratified
according to estrogen receptor status (positive vs negative vs unknown), nodal
status (0 positive nodes vs 1-3 positive nodes vs 4-9 positive nodes vs at
least 10 positive nodes), tumor size (no more than 5 cm vs more than 5 cm vs
unknown), and type of prior surgery (mastectomy vs breast conservation
surgery). Patients are randomized to one of four treatment arms. - Arm I: Patients receive doxorubicin IV and cyclophosphamide IV every 3
weeks for 4 courses (weeks 1-12). Beginning at week 13, patients receive
paclitaxel IV over 3 hours every 3 weeks for 4 courses.
- Arm II: Patients receive doxorubicin and cyclophosphamide as in arm I.
Beginning at week 13, patients receive paclitaxel IV over 1 hour weekly for 12
weeks.
- Arm III: Patients receive doxorubicin and cyclophosphamide as in arm I.
Beginning at week 13, patients receive docetaxel IV over 1 hour every 3 weeks
for 4 courses.
- Arm IV: Patients receive doxorubicin and cyclophosphamide as in arm I.
Beginning at week 13, patients receive docetaxel IV over 1 hour weekly for 12
weeks.
Within 4 weeks after completion of chemotherapy, patients with estrogen
and/or progesterone receptor positive tumors receive oral tamoxifen daily for
5 years. After completion of all chemotherapy, patients with prior segmental
mastectomy receive radiotherapy once daily 5 days per week for 5-6 weeks.
Patients with prior modified radical mastectomy may receive radiotherapy after
chemotherapy completion at the investigator's discretion. Patients are followed every 3 months for 2 years, every 6 months for 3
years, and then annually thereafter. Published ResultsSparano JA, Wang M, Martino S, et al.: Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 358 (16): 1663-71, 2008.[PUBMED Abstract] Sparano JA, Wang M, Martino S, et al.: Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in patients with axillary node-positive or high-risk node-negative breast cancer: results of North American Breast Cancer Intergroup Trial E1199. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-48, 2005.
Trial Contact Information
Trial Lead Organizations Eastern Cooperative Oncology Group | | | Joseph Sparano, MD, Protocol chair | | | |
North Central Cancer Treatment Group | | | Edith Perez, MD, Protocol chair | | | |
Southwest Oncology Group | | | Silvana Martino, DO, Protocol chair | | | |
Cancer and Leukemia Group B | | | Vicky Jones, MD, Protocol chair(Contact information may not be current) | | | |
Registry Information | | Official Title | | A Phase III Study of Doxorubicin-Cyclophosphamide Therapy Followed by Paclitaxel or Docetaxel Given Weekly or Every 3 Weeks in Patients with Axillary Node-Positive Breast Cancer | | Trial Start Date | | 1999-10-13 | | Trial Completion Date | | 2008-04-17 | | Registered in ClinicalTrials.gov | | NCT00004125 | | Date Submitted to PDQ | | 1999-09-29 | | Information Last Verified | | 2008-08-12 | | NCI Grant/Contract Number | | CA21115 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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