Comparison of Combination Chemotherapy Regimens in Treating Older Women Who Have Undergone Surgery for Breast Cancer
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Purpose
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them in different ways after surgery may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective in treating older women with breast cancer.
PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens to see how well they work in treating older women who have undergone surgery for breast cancer.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer |
Drug: Standard Treatment Drug: capecitabine |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Randomized Trial of Adjuvant Chemotherapy With Standard Regimens, Cyclophosphamide, Methotrexate and Fluorouracil - (CMF) or Doxorubicin and Cyclophosphamide - (AC), Versus Capecitabine in Women 65 Years and Older With Node Positive or Node-Negative Breast Cancer |
- Relapse-free Survival Rates at 2.4 Years [ Time Frame: randomization until date of first event, or date last known to be event free if no event was reported (up to 5 years) ] [ Designated as safety issue: No ]Percentage of participants who were alive and relapse-free at time of analysis were counted as "Alive without relapse" at 2.4 years. Participants who had a first local recurrence, first distant metastasis or death from any cause were counted as "relapse, first occurrence". These rates were estimated using the Kaplan Meier method
- Overall Survival Rate at 2.4 Years [ Time Frame: Time from registration to death (up to 15 years) ] [ Designated as safety issue: No ]Percentage of patients who were alive at 2.4 years. This rate was estimated using the Kaplan Meier method.
- Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment. [ Time Frame: Reported during protocol treatment after each cycle ] [ Designated as safety issue: Yes ]
The National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 2.0 was used to evaluate toxicity.
Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.
| Enrollment: | 633 |
| Study Start Date: | September 2001 |
| Study Completion Date: | November 2012 |
| Primary Completion Date: | May 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Standard Chemotherapy
Patient/Physician choice of cyclophosphamide + MTX + 5-FU OR Cyclophosphamide + doxorubicin |
Drug: Standard Treatment
Cyclophosphamide 100 mg/sq m PO d 1-14 + MTX 40 mg/sq m IV push d 1 & 8 and 5-FU 600 mg/sq m IV push d 1 & 8 q 28 days for 6 cycles OR doxorubicin 60 mg/sq m IV d 1 + cyclophosphamide 600 mg/sq m IV d 1 q 21 d for 4 cycles
Other Name: doxorubicin = adriamycin
|
|
Experimental: Capecitabine
Treatment with capecitabine
|
Drug: capecitabine
2000 mg/sq m PO d 1-14, 7 day rest then repeat for a total of 6 cycles
|
Detailed Description:
OBJECTIVES:
- Compare the effectiveness of adjuvant chemotherapy comprising standard cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin and cyclophosphamide (AC) vs oral capecitabine, in terms of disease-free and overall survival, in elderly women with operable adenocarcinoma of the breast.
- Compare the quality of life and physical functioning of patients treated with these regimens.
- Compare the toxicity of these regimens in these patients.
- Evaluate the adherence of older patients to an oral chemotherapy regimen.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (65 to 69 vs 70 to 80 vs over 80), performance status (0-1 vs 2), and HER2 status (positive vs negative vs unknown). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients with insufficient left ventricular ejection fraction (LVEF) are assigned to group A. Patients with normal LVEF are assigned to group A or B based on physician/patient choice.
- Group A (CMF): Patients receive oral cyclophosphamide (CTX) daily on days 1-14 and methotrexate IV and fluorouracil IV on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
- Group B (AC): Patients receive doxorubicin IV and CTX IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
Beginning within 12 weeks after treatment in arm I or II, patients with estrogen or progesterone receptor-positive disease receive oral tamoxifen or an aromatase inhibitor daily for 5 years.
Beginning 4-6 weeks after treatment in arm I or II, eligible patients who previously underwent breast conservation surgery undergo radiotherapy.
Quality of life is assessed at baseline; at 6 weeks (group B), 9 weeks (arm II), or 12 weeks (group A); and then at 1, 12, 18, and 24 months after study.
Drug adherence is assessed at 9 weeks during study (arm II).
Patients are followed at 1 month, every 6 months for 2 years, and then annually for 15 years.
PROJECTED ACCRUAL: A total of 600-1,800 patients (300-900 per treatment arm) will be accrued for this study within 2-6 years.
Eligibility| Ages Eligible for Study: | 65 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically proven operable adenocarcinoma of the breast*
Stage I-IIIC disease
- T1-4 (tumor size ≥ 1 cm), N0, M0 OR
- T1-4, N1-3, M0 NOTE: *Bilateral, synchronous breast cancer allowed provided 1 primary tumor meets the staging criteria
Must have undergone 1 of the following within the past 12 weeks:
Modified radical mastectomy
No evidence of gross or microscopic invasive tumor at the surgical resection margins
- Close margins (tumor less than 1 mm from margin) allowed
Lumpectomy (clear margins preferred)
- Ductal carcinoma in situ or lobular carcinoma in situ at the surgical resection margin allowed
- No invasive tumor at the final resection margin
Any number of previously excised nodes allowed
- Axillary node dissection not required
HER2/neu positive, negative, or unknown
- Patients with HER2 positive tumors by immunohistochemistry 3+ staining or that demonstrate gene amplification by fluorescence in situ hybridization are eligible to receive trastuzumab (Herceptin) on study
Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age:
- 65 and over
Sex:
- Female
Menopausal status:
- Postmenopausal
Performance status:
- 0-2
Life expectancy:
- More than 5 years
Hematopoietic:
- Granulocyte count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin no greater than upper limit of normal
Renal:
- Creatinine clearance at least 30 mL/min
Cardiovascular:
- No uncontrolled cardiac disease that would preclude study entry
- Left ventricular ejection fraction at least lower limit of normal (arm I, group B only)
Other:
- HIV negative
No other concurrent active malignancy except nonmelanoma skin cancer
- Disease considered not currently active if completely treated with less than a 30% risk of relapse
- No psychiatric illness that would preclude informed consent
- No other medical condition (e.g., uncontrolled infection) that would preclude study entry
- No hypersensitivity to fluorouracil
- No known dihydropyrimidine dehydrogenase deficiency
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- No prior chemotherapy for breast cancer
- No other concurrent chemotherapy
Endocrine therapy:
- Up to 4 weeks of prior tamoxifen for current breast cancer allowed
- Prior tamoxifen or raloxifene for chemoprevention (e.g., breast cancer prevention study) or other indications (including prior breast cancer) allowed but must be discontinued before study entry
- No concurrent hormonal therapy except steroids for adrenal failure, hormones for non-disease related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic
Radiotherapy:
- Not specified
Surgery:
- See Disease Characteristics
Other:
- No concurrent dexrazoxane
- No concurrent bisphosphonates except for treatment of osteoporosis
Contacts and Locations
Show 334 Study Locations| Study Chair: | Hyman B. Muss, MD | Fletcher Allen Health Care - University Health Center Campus |
| Study Chair: | Antonio C. Wolff, MD | Sidney Kimmel Comprehensive Cancer Center |
| Study Chair: | Julie R. Gralow, MD | Seattle Cancer Care Alliance |
| Study Chair: | Debjani Grenier, MD | CancerCare Manitoba |
More Information
Additional Information:
Publications:
| Responsible Party: | Cancer and Leukemia Group B |
| ClinicalTrials.gov Identifier: | NCT00024102 History of Changes |
| Other Study ID Numbers: | CDR0000068891, U10CA031946, CALGB-49907, ECOG-CALGB-49907, CAN-NCIC-MAC1, SWOG-CALGB-49907 |
| Study First Received: | September 13, 2001 |
| Results First Received: | November 20, 2012 |
| Last Updated: | December 21, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Cancer and Leukemia Group B:
|
stage I breast cancer stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Cyclophosphamide Fluorouracil Capecitabine Doxorubicin Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antibiotics, Antineoplastic Antimetabolites, Antineoplastic Antimetabolites |
ClinicalTrials.gov processed this record on May 23, 2013