A Study of Cyclophosphamide, Methotrexate, Fluorouracil (CMF) for People With Breast Cancer

STUDY OF DOSE DENSE CMF (Cyclophosphamide, Methotrexate, Fluorouracil) as an Alternative to AC (Doxorubicin, Cyclophosphamide) in 2 Regimens in EARLY STAGE BREAST CANCER for Patients Greater or Equal to 70

The purpose of this study is to find out if it is practical (feasible) to give dose-dense CMF (cyclophosphamide, methotrexate, and fluorouracil) in two standard chemotherapy regimens in people with breast cancer, age 70 and older.

Inclusion Criteria:

• Patients must have histologically confirmed adenocarcinoma of the breast confirmed at MSK. The patient must have had diagnostic biopsy or completion of primary surgical management, within 3 months of enrollment. Results of HER-2/neu, estrogen receptor, and progesterone receptor are required for study entry.
• Patients must be ≥ 70 years of age.
• Patients must have ECOG performance status >2 (Karnofsky score of ≥ 60%).
• Patients may have received hormonal therapy for the purpose of chemoprevention.
• Adjuvant/neoadjuvant chemotherapy decision to treat based on the discretion of investigator
• Cohort 1 only: Patients have any histology except Her 2 Neu positive in the adjuvant or neoadjuvant setting
• Cohort 2 only: Patients have triple negative (ER- (10%) PR-Her 2 Neu -) in the neoadjuvant setting
• Cohort 2 only: Patients have received at least 1 dose of carboplatin/paclitaxel +/- pembrolizumab in the neoadjuvant setting

Required Organ Function

Adequate hematologic function defined as follows:

• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
• Platelets ≥ 100,000 cells/mm3

Adequate renal function defined as follows:

° Creatinine clearance (CrCL) of >30 mL/min by the Cockcroft-Gault formula:

CrCl (mL/min) = [([140 - age(years)] x weight (kg))/72 x creatinine (mg/dL)] (x 0.85 for female patients)

Adequate hepatic function defined as follows:

• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)

• AST and ALT ≤3 x institutional ULN

  • Patients or their Legally Authorized Representative must give written, informed consent indicating their understanding and willingness to participate in the study.

Exclusion Criteria:

• Stage IV breast cancer
• CARG score- high Frail 4 or more as assessed by CAIT
• Her 2 Neu positive 3+/amplified breast cancer
• No prior chemotherapy within 1 year of study enrollment
• Cohort 2 only: patients may not receive pembrolizumab during dd CMF treatment