Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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.

Further Study Information

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 Criteria

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

Trial Contact Information

Trial Lead Organizations/Sponsors

Cancer and Leukemia Group B

Hyman Bernard Muss

Study Chair

Antonio C. Wolff

Study Chair

Julie R. Gralow

Study Chair

Debjani Grenier

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00024102
Information obtained from ClinicalTrials.gov on January 30, 2013

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