Comparison of Combination Chemotherapy Regimens in Treating Older Women Who Have Undergone Surgery for Breast Cancer

This study has been completed.
Sponsor:
Collaborators:
Eastern Cooperative Oncology Group
Southwest Oncology Group
NCIC Clinical Trials Group
Information provided by (Responsible Party):
Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:
NCT00024102
First received: September 13, 2001
Last updated: December 21, 2012
Last verified: December 2012
  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

Resource links provided by NLM:


Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00024102

  Show 334 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Southwest Oncology Group
NCIC Clinical Trials Group
Investigators
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:
Kornblith AB, Archer L, Lan L, et al.: Quality of life of early stage breast cancer patients 65 years old or older randomized to standard chemotherapy or capecitabine: A Cancer and Leukemia Group B Study (CALGB 49907). [Abstract] 32nd Annual San Antonio Breast Cancer Symposium, December 9-13, 2009, San Antonio, Texas. A-5035, 2009.
Muss HB, Berry DL, Cirrincione C, et al.: Standard chemotherapy (CMF or AC) versus capecitabine in early-stage breast cancer (BC) patients aged 65 and older: results of CALGB/CTSU 49907. [Abstract] J Clin Oncol 26 (Suppl 15): A-507, 2008.
Partridge AH, Archer LE, Kornblith AB, et al.: CALGB 60104: adherence with adjuvant capecitabine among women age 65 and older with early stage breast cancer treated on CALGB 49907. [Abstract] J Clin Oncol 26 (Suppl 15): A-6542, 2008.

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
Capecitabine
Liposomal doxorubicin
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
Antimetabolites, Antineoplastic
Antimetabolites
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014