Low-dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-negative Early Breast Cancer (22-00)
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| ClinicalTrials.gov Identifier: NCT00022516 |
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Recruitment Status :
Completed
First Posted : January 27, 2003
Results First Posted : December 11, 2015
Last Update Posted : September 16, 2016
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Sponsor:
ETOP IBCSG Partners Foundation
Information provided by (Responsible Party):
ETOP IBCSG Partners Foundation
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Brief Summary:
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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Breast Cancer | Drug: Cyclophosphamide Drug: Methotrexate | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1086 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (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 |
| Study Start Date : | November 2000 |
| Actual Primary Completion Date : | January 2015 |
| Actual Study Completion Date : | August 2016 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
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No Intervention: No-CM
No further chemotherapy following standard adjuvant chemotherapy.
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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)
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Drug: Cyclophosphamide
50 mg/day orally continuously for 1 year
Other Names:
Drug: Methotrexate 2.5 mg twice/day orally days 1 and 2 of every week for 1 year
Other Name: Trexall |
Primary Outcome Measures :
- Disease-free Survival [ Time Frame: 5-year estimates, reported at a median follow-up of 6.9 years ]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 ]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 ]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 ]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.
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| Ages Eligible for Study: | 18 Years to 120 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
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Histologically confirmed stage I, II, or III breast cancer
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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
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- No bilateral breast cancer (except in situ carcinoma) or suspicious mass in opposite breast that has not been proven benign
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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
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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
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Hormone receptor status:
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Estrogen and progesterone receptor negative
- Less than 10% positive tumor cells by immunohistochemistry
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00022516
Locations
Show 36 study locations
Sponsors and Collaborators
ETOP IBCSG Partners Foundation
Investigators
| Study Chair: | Marco Colleoni, MD | European Institute of Oncology |
Publications of Results:
| Responsible Party: | ETOP IBCSG Partners Foundation |
| ClinicalTrials.gov Identifier: | NCT00022516 |
| Other Study ID Numbers: |
CDR0000068827 IBCSG-22-00 ( Other Identifier: IBCSG ) 2005-005666-36 ( EudraCT Number ) EU-20119 ( Registry Identifier: NCI Liaison Office, Brussels ) |
| First Posted: | January 27, 2003 Key Record Dates |
| Results First Posted: | December 11, 2015 |
| Last Update Posted: | September 16, 2016 |
| Last Verified: | August 2016 |
Keywords provided by ETOP IBCSG Partners Foundation:
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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:
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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 |