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

This study has been completed.
Sponsor:
Collaborators:
NCIC Clinical Trials Group
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00024102
First received: September 13, 2001
Last updated: June 23, 2015
Last verified: June 2015
  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 Alliance for Clinical Trials in Oncology:

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
  1. Patients with operable, histologically confirmed adenocarcinoma of the female breast.
  2. TNM Stage per AJCC Cancer Staging Manual 6th edition:

    • T1-4 (Tumor size > 1 cm), N0, M0 or T1-4, N1-3, M0
    • Patients with bilateral, synchronous breast cancer are eligible as long as one primary tumor meets the criteria above.
  3. Patients with HER2/neu positive, negative or unknown disease are eligible for this trial.

    Patients whose tumors are HER2 positive by either immunohistochemistry 3+ staining or demonstrate gene amplification by FISH will be eligible to receive trastuzumab, as outlined in the protocol.

  4. Age 65 years or older
  5. Performance status 0-2 (Common Toxicity Criteria).
  6. Prior treatment:

    • Surgical resection -

      • All tumor should be removed by either a modified radical mastectomy or a lumpectomy. Patients must be registered ≤ 84 days from mastectomy or within 84 days of axillary dissection if patient's most extensive breast surgery was a breast sparing procedure.
      • Node dissection: Axillary node dissection is not required. Management of the axilla is at the discretion of the treating physician. There is no restriction on eligibility based on the number of nodes removed.
      • Mastectomy: There should be no evidence of gross or microscopic invasive tumor at the surgical resection margins noted in the final surgery or pathology reports for patients who have had a modified radical mastectomy. Patients with close margins (tumor < 1 mm from margin) are eligible.
      • Segmental mastectomy (lumpectomy): Although clear margins are preferable, DCIS or LCIS at the surgical resection margin will not render a patient who has undergone a segmental mastectomy ineligible for this study. Invasive tumor at the final resection margin will render a patient ineligible.
    • No prior chemotherapy for this malignancy.
    • Patients with a history of hypersensitivity to 5-FU or known dihydropyrimidine dehydrogenase (DPD) deficiency are not eligible to participate.
    • Patients may receive up to four weeks of tamoxifen therapy for this malignancy and still be eligible for study entry. Patients who received tamoxifen or raloxifene for purposes of chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (including previous breast cancer) are eligible. Tamoxifen or raloxifene therapy should be discontinued before the patient is enrolled on this study.
  7. Required Initial Laboratory Data:

    • Granulocytes > 1,500/µl
    • Platelet count ≥100,000/µl
    • Calculated Creatinine Clearance > 30 mL/min
    • Total bilirubin ≤ ULN
  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
Alliance for Clinical Trials in Oncology
NCIC Clinical Trials Group
Investigators
Study Chair: Hyman B. Muss, MD University of Vermont
  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: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00024102     History of Changes
Other Study ID Numbers: CALGB-49907, U10CA031946, CAN-NCIC-MAC1, CDR0000068891
Study First Received: September 13, 2001
Results First Received: November 20, 2012
Last Updated: June 23, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Trials in Oncology:
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
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Capecitabine
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Alkylating Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on July 28, 2015