Low-dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-negative Early Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Cyclophosphamide; Methotrexate
Intervention description: 50 mg/day orally continuously for 1 year; 2.5 mg twice/day orally days 1 and 2 of every week for 1 year
Intervention MeSH terms: Cyclophosphamide; Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1086.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: 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

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.
    

Eligibility 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