Official Title: “Pilot Study of Dose Dense Adjuvant CMF (Cyclophosphamide, Methotrexate, Fluorouracil) at 14 and 10-11 Day Intervals for Women With Early Stage Breast Cancer”

CMF (cyclophosphamide, methotrexate, fluorouracil) is used to treat early stage breast cancer. The combination, of these three drugs, has been used for approximately 30 years in the treatment of breast cancer, and has been shown to be safe and effective. It is usually given every 3 weeks. Doctors believe, based on other breast cancer trials, that giving this type of chemotherapy in a shorter amount of time, every 2 weeks or sooner, instead of every 3 weeks, may be better. The purpose of this study is to test the safety of these drugs, given every 2 weeks or sooner, to treat breast cancer. Other breast cancer chemotherapy regimens have shown to be more beneficial when the drugs are given more frequently.

Study Type: Interventional

Study Design: Treatment, Open Label, Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: January 2011

Intervention(s) in this Clinical Trial

• Drug: cyclophosphamide, methotrexate, fluorouracil, PEG-filgrastim
  • C (cyclophosphamide) 600 mg/m2 M (methotrexate) 40 mg/m2 F (fluorouracil) 600 mg/m2 P (PEG-filgrastim ) 6 mg. Eight doses of CMF q 14 days with PEG-filgrastim administered approximately 24 hours after chemotherapy. Day 14, is also considered day 1 of the next cycle.
• Drug: cyclophosphamide, methotrexate, fluorouracil, PEG-filgrastim
  • If Cohort 1 is deemed safe according to stopping criteria listed, the next cohort of patients, Cohort 2, C (cyclophosphamide) 600 mg/m2 M (methotrexate) 40 mg/m2 F (fluorouracil) 600 mg/m2 N (filgrastim/Neupogen ®) 300 mcg or 480 mcg. Eight doses of CMF q 10-11 days with filgrastim (Neupogen®) given days 1-5 beginning the day after chemotherapy. 300 μg/kg for patients < 60 kg or 480 μg for patients > or = to 60 kg subcutaneous from day 2 until day 8 (7 days).

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • This is a pilot study using 8 cycles of CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2), at 14 day intervals supported by PEG-filgrastim for a cohort of 38 patients. A safety analysis will then be performed.
• Experimental: 2
  • Cohort 2, will be treated at 10-11 day intervals and supported by filgrastim.

Primary Measures

• The primary objective of the study is to evaluate the feasibility and safety of this dose dense regimen. Delivered dose-intensity and specific toxicities will be assessed.
  • Time Frame: conclusion of study
    Safety Issue?: Yes

Inclusion Criteria:

• Patients must have histologically confirmed adenocarcinoma of the breast confirmed at
• MSKCC within 3 months of enrollment. Patients with inflammatory breast cancer are not eligible for the study. Pathology will be assessed in the standard fashion. Results of HER-2/neu, estrogen receptor, and progesterone receptor are required for study entry.
• The patient cannot be Her-2/neu over-expressing either by immunohistochemistry or FISH as per hospital laboratory standard whether institutional or outside laboratory.
• Patients must be > than or equal to 18 years of age
• Patients must have a Karnofsky score of > than or equal to 80
• Patients may have received hormonal therapy for the purpose of chemoprevention but must be willing to discontinue at least 24 hours prior to enrollment and while participating in this trial.
• Patients will have completed their definitive breast surgery (mastectomy or breast conserving surgery)
• Patients must be ready to begin therapy within 84 days from the final surgical procedure required to treat their primary tumor
• Patients must be stage I-II
• Absolute neutrophil count (ANC) > than or equal to 1500/µL and platelet count > than or equal to 100,000/µL
• Total bilirubin must be < than or equal to 1.1 mg/dL or within normal institutional limits if outside MSKCC. Transaminases (SGOT/AST and/or SGPT/ALT) may be up to < than or equal to 92.5 U/L or < than or equal to 2.5 x institutional upper limit of normal (ULN) if alkaline phosphatase is < than or equal to ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are < than or equal to ULN.
• Serum creatinine must be within 0.6-1.3 mg/dL or within normal institutional limits if outside MSKCC.
• Patients must be willing to discontinue sex hormonal therapy e.g., birth control pills, ovarian hormonal replacement therapy, etc., prior to enrollment. Women of childbearing potential must be willing to consent to using effective contraception while on treatment and for a reasonable period thereafter.
• Patients must give written, informed consent indicating their understanding and willingness to participate in the study.
• Brachytherapy after lumpectomy is permitted.

Exclusion Criteria:

• Stage III-IV breast cancer
• Prior chemotherapy or radiation therapy is excluded except for brachytherapy.Radiation for patients on this protocol will be given, if indicated, after the completion of chemotherapy.
• Pregnant or lactating patients
• Patients with a concurrently active second malignancy, other than adequately treated non-melanoma skin cancers or in situ cervical cancer. Patients with other non-mammary malignancies must have been disease-free for at least five years.
• Patients with unstable angina, congestive heart failure, current use of digitalis, betablockers, or calcium blockers for therapy of congestive heart failure, arrhythmia requiring medical therapy, or with a history of a myocardial infarction within 12 months.
• Patients with a psychiatric illness that would prevent them from understanding the nature of the investigational therapy and complying with protocol requirements.
• Patients with concurrent medical conditions, which, in the judgment of the investigator, would make them inappropriate candidates for study enrollment
• Patients with active, unresolved infections
• Patients that have known sensitivity to E. coli derived proteins, PEG-filgrastim, filgrastim, or any component products.
• Patients must be Her 2/neu non-over-expressing.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Memorial Sloan-Kettering Cancer Center

Overall Clinical Trial Officials and Contacts

Pamela Drullinsky, MD Principal Investigator Memorial Sloan-Kettering Cancer Center  

Overall Contact: Pamela Drullinsky, MD  drullinp@mskcc.org

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00615901

Study ID Number: 07-133

ClinicalTrials.gov Identifier: NCT00615901

Health Authority: United States: Institutional Review Board

Memorial Sloan-Kettering Cancer Center