RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known if chemotherapy followed by peripheral stem cell transplantation is more effective than chemotherapy alone in treating metastatic breast cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of combination chemotherapy plus peripheral stem cell transplantation with that of chemotherapy alone in treating women who have stage IV breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer	Drug: carboplatin  Drug: cyclophosphamide  Drug: docetaxel  Drug: doxorubicin  Drug: etoposide  Drug: filgrastim  Drug: fluorouracil  Drug: ifosfamide  Drug: methotrexate  Drug: thiotepa	Phase II

Further Study Details: 

OBJECTIVES: I. Compare the efficacy of multi-course high-dose chemotherapy with autologous peripheral blood stem cell transplantation versus standard-dose chemotherapy in women with metastatic breast cancer. II. Compare the five year event-free survival, in terms of time to progression or time to death due to toxic effects, in patients treated with these regimens. III. Compare the response rate and overall survival of patients treated with these regimens. IV. Compare the toxicity of these regimens in this patient population.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms. Arm I: Patients receive docetaxel and doxorubicin once followed by filgrastim (G-CSF) daily for approximately 1 week. Treatment repeats approximately every 3 weeks for 4 courses. Patients then receive cyclophosphamide, methotrexate, and fluorouracil on days 7 and 8 every 4 weeks for 4 courses. Arm II: Patients receive docetaxel, doxorubicin, and G-CSF as in arm I for 3 courses. Patients undergo leukapheresis daily for 3 or 4 days. Patients then receive 1 course of ifosfamide, etoposide, and carboplatin daily for 4 days when blood counts recover, followed by 1 course of cyclophosphamide and thiotepa daily for 4 days. Patients undergo peripheral blood stem cell reinfusion following each course.

PROJECTED ACCRUAL: A total of 264 patients (132 per arm) will be accrued for this study.

Ages Eligible for Study:  18 Years   -   59 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed stage IV breast carcinoma
• Bone metastasis as only form of metastatic disease allowed
• No evidence of bone marrow involvement by aspirate or biopsy
• No brain metastases
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy for metastatic disease; No prior mitomycin, nitrosoureas, or platinum coordination complexes; Prior adjuvant chemotherapy allowed if completed more than 6 months prior to relapse with metastases; No more than 300 mg/m2 prior doxorubicin or 450 mg/m2 prior epirubicin
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy to the brain or marrow-bearing pelvis; Prior radiotherapy to lower pelvis allowed if the upper border of the radiotherapy field is below the upper border of the acetabulum; No other prior radiotherapy to the pelvis
• Surgery: At least 2 weeks since prior major surgery
• Other: No other concurrent anti-cancer therapy

--Patient Characteristics--

• Age: 18 to 59
• Sex: Female
• Menopausal status: Not specified
• Performance status: Karnofsky 80-100%
• Life expectancy: More than 3 months
• Hematopoietic: Absolute neutrophil count greater than 1,500/mm3; Platelet count greater than 100,000/mm3; Hemoglobin greater than 9 g/dL; PT normal; Activated PTT normal
• Hepatic: Bilirubin normal (unless benign congenital hyperbilirubinemia is present); No AST/ALT greater than 1.5 times upper limit of normal (ULN) together with alkaline phosphatase greater than 2.5 times ULN; No active hepatitis B or C
• Renal: Creatinine normal
• Cardiovascular: Ejection fraction normal by MUGA or echocardiogram; No active heart disease; No prior myocardial infarction or other manifestation of coronary artery disease
• Other: More than 1,000 calories/day oral intake; HIV negative; No active serious medical or psychiatric disease; No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix; No allergy to polysorbate 80 or E. coli-derived products; No peripheral neuropathy greater than grade 2; Not pregnant; Negative pregnancy test

New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States

Study chairs or principal investigators

Linda T. Vahdat,  Study Chair,  Herbert Irving Comprehensive Cancer Center   

Study ID Numbers:  CDR0000068504; CPMC-IRB-9244; NCI-G01-1922
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  March 3, 2001
ClinicalTrials.gov Identifier:  NCT00012311
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08