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Low-dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-negative Early Breast Cancer (22-00)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
International Breast Cancer Study Group
ClinicalTrials.gov Identifier:
NCT00022516
First received: August 10, 2001
Last updated: August 5, 2016
Last verified: August 2016
  Purpose
This randomized, phase III trial was designed to test the efficacy of a low-dose chemotherapy-maintenance regimen, hypothesized to have anti-angiogenic activity, administered following standard chemotherapy in patients with early breast cancer whose tumors are hormone receptor negative.

Condition Intervention Phase
Breast Cancer
Drug: Cyclophosphamide
Drug: Methotrexate
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: Low-dose Cytotoxics as "Anti-angiogenesis Treatment" Following Adjuvant Induction Chemotherapy for Patients With ER-negative and PgR-negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by International Breast Cancer Study Group:

Primary Outcome Measures:
  • Disease-free Survival [ Time Frame: 5-year estimates, reported at a median follow-up of 6.9 years ] [ Designated as safety issue: No ]
    Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to the first appearance of one of the following: invasive breast cancer recurrence at local, regional, or distant site, invasive contralateral breast cancer, second (non-breast) invasive cancer, or death without cancer event; or censored at date of last follow-up.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 5-year estimates, reported at a median follow-up of 6.9 years ] [ Designated as safety issue: No ]
    Estimated percentage of patients alive and disease-free at 5 years from randomization, where overall survival is defined as the time from randomization to death from any cause; or censored at date last known alive.

  • Distant Recurrence-free Interval [ Time Frame: 5-year estimates, reported at a median follow-up of 6.9 years ] [ Designated as safety issue: No ]
    Estimated percentage of patients alive and disease-free at 5 years from randomization, where distant recurrence-free Interval is defined as the time from randomization to invasive breast cancer recurrence at distant site, or invasive contralateral breast cancer; or censored at date of last follow up.

  • Breast Cancer-free Interval [ Time Frame: 5-year estimates, reported at a median follow-up of 6.9 years ] [ Designated as safety issue: No ]
    Estimated percentage of patients alive and disease-free at 5 years from randomization, where breast cancer-free interval is defined as the time from randomization to invasive breast cancer recurrence at local, regional, or distant site, or invasive contralateral breast cancer; or censored at date of last follow up.


Enrollment: 1086
Study Start Date: November 2000
Study Completion Date: August 2016
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: No-CM
No further chemotherapy following standard adjuvant chemotherapy.
Experimental: CM-Maintenance
12-month CM-maintenance regimen (C, cyclophosphamide 50 mg/day orally continuously and M, methotrexate 2.5 mg twice/day orally days 1 and 2 of every week for 1 year)
Drug: Cyclophosphamide
50 mg/day orally continuously for 1 year
Other Names:
  • Endoxan
  • Cytoxan
Drug: Methotrexate
2.5 mg twice/day orally days 1 and 2 of every week for 1 year
Other Name: Trexall

Detailed Description:

PURPOSE:

  • Evaluate a low-dose cyclophosphamide and methotrexate chemotherapy-maintenance regimen in early breast cancer.
  • Compare the disease-free survival, overall survival, and systemic disease-free survival of patients treated with these regimens.
  • Compare the toxic effects of these regimens in these patients.

OUTLINE:

This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, menopausal status (pre vs post), and approved induction chemotherapy (anthracycline and cyclophosphamide vs other agents). Treatment duration is 12 months of low-dose chemotherapy-maintenance regimen (CM-maintenance) vs no chemotherapy-maintenance regimen (no-CM) following standard adjuvant chemotherapy. Patients are randomized to one of two treatment arms. Patients are followed every 6 months for 5 years, and yearly follow-up thereafter.

  Eligibility

Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed stage I, II, or III breast cancer

    • T1-3, N0-2, M0

      • Patients with sentinel node biopsy positive disease must have undergone axillary dissection
      • Tumor must be confined to the breast without detected metastases elsewhere
    • T4 disease with minimal dermal invasion allowed
    • No T4 disease with ulceration of skin, infiltration of skin (except pathologically minimal dermal involvement), peau d'orange, or inflammatory breast cancer
  • No bilateral breast cancer (except in situ carcinoma) or suspicious mass in opposite breast that has not been proven benign
  • No distant metastases

    • No skeletal pain of unknown cause, elevated alkaline phosphatase, or bone scan showing hot spots that cannot be ruled out as metastases by x-ray, MRI, and/or CT
  • Must have undergone prior total mastectomy OR breast-conserving procedure (e.g., lumpectomy, quadrantectomy, or partial mastectomy with negative margins) with radiotherapy planned

    • Patients must begin or have begun an approved induction chemotherapy regimen within 8 weeks after definitive surgery
  • Negative surgical margins
  • Axillary clearance with at least 6 lymph nodes examined OR negative sentinel node biopsy
  • Known HER2 status by immunohistochemistry or fluorescence in situ hybridization
  • Hormone receptor status:

    • Estrogen and progesterone receptor negative

      • Less than 10% positive tumor cells by immunohistochemistry

PATIENT CHARACTERISTICS:

Age:

  • Not specified

Sex:

  • Not specified

Menopausal status:

  • Premenopausal, defined as less than 6 months since last menstrual period (LMP) AND no prior bilateral ovariectomy AND not on estrogen replacement (OR under age 50) OR
  • Postmenopausal, defined as prior bilateral ovariectomy OR more than 12 months since LMP without prior hysterectomy (OR age 50 and over)

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • WBC greater than 3,000/mm3
  • Platelet count greater than 100,000/mm3

Hepatic:

  • See Disease Characteristics
  • Bilirubin less than 2.0 mg/dL
  • ALT less than 1.5 times upper limit of normal OR AST less than 60 IU/L

Renal:

  • Creatinine less than 1.2 mg/dL

Other:

  • Not pregnant or lactating within the past 6 months
  • Fertile patients must use effective barrier contraception
  • No other prior or concurrent malignancy except adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or contralateral or ipsilateral in situ breast carcinoma
  • No psychiatric or addictive disorders that would preclude study
  • No non-malignant systemic disease that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Prior trastuzumab (Herceptin) allowed

Chemotherapy:

  • See Disease Characteristics
  • No prior adjuvant or neoadjuvant chemotherapy for breast cancer

Endocrine therapy:

  • No prior endocrine therapy for breast cancer or prevention
  • No prior tamoxifen or raloxifene for breast cancer

Radiotherapy:

  • No prior radiotherapy for breast cancer except primary irradiation

Surgery:

  • See Disease Characteristics

Other:

  • No prior preventative therapy for breast cancer
  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: NCT00022516

  Show 36 Study Locations
Sponsors and Collaborators
International Breast Cancer Study Group
Investigators
Study Chair: Marco Colleoni, MD European Institute of Oncology
  More Information

Publications:
Responsible Party: International Breast Cancer Study Group
ClinicalTrials.gov Identifier: NCT00022516     History of Changes
Other Study ID Numbers: CDR0000068827  IBCSG-22-00  2005-005666-36  EU-20119 
Study First Received: August 10, 2001
Results First Received: November 6, 2015
Last Updated: August 5, 2016
Health Authority: Switzerland: Swissmedic
Romania: National Medicines Agency
Belgium: Federal Agency for Medicinal Products and Health Products
Nigeria: The National Agency for Food and Drug Administration and Control
Italy: The Italian Medicines Agency
Sweden: Medical Products Agency

Keywords provided by International Breast Cancer Study Group:
stage IA breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IB breast cancer
estrogen receptor-negative breast cancer
progesterone receptor-negative breast cancer
triple-negative breast cancer
low-dose maintenance chemotherapy
stroma
angiogenesis

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Methotrexate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on December 09, 2016