RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Combining chemotherapy with autologous peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells.

PURPOSE: Phase II trial to compare the effectiveness of two regimens of chemotherapy and filgrastim plus stem cell transplantation in treating patients who have previously untreated stage III or stage IV breast cancer.

Condition	Treatment or Intervention	Phase
stage IIIB breast cancer stage IV breast cancer stage IIIA breast cancer recurrent breast cancer	Drug: carboplatin  Drug: cyclophosphamide  Drug: filgrastim  Drug: ifosfamide  Drug: thiotepa	Phase II

Further Study Details: 

OBJECTIVES: I. Assess the antitumor response, survival, and disease free survival following high dose carboplatin, ifosfamide, and thiotepa with autologous peripheral blood stem cell (PBSC) support and consolidation radiotherapy to sites of pretreatment bulk disease in patients with previously treated advanced breast cancer.

II. Assess the toxicity of high dose chemotherapy in these patients.

III. Compare the effectiveness of PBSC mobilization with high dose cyclophosphamide and filgrastim (G-CSF) vs G-CSF alone in this patient population.

PROTOCOL OUTLINE: Patients are assigned to 1 of 2 peripheral blood stem cell (PBSC) mobilization groups at the discretion of the attending physician:

Group 1: Patients receive high dose cyclophosphamide IV over 6 hours and filgrastim (G-CSF) subcutaneously (SQ) daily beginning 24 hours after completion of cyclophosphamide and continuing until 3 days after blood counts have recovered and until PBSC are harvested.

Group 2: Patients receive G-CSF SQ daily alone until PBSC are harvested.

Both groups: PBSC are harvested on days 15-19 after cyclophosphamide infusion or when blood counts recover. Patients receive high dose carboplatin IV continuously, ifosfamide IV over 4 hours, and thiotepa IV over 1 hour on days -5 to -3. PBSC are reinfused beginning 48 hours after completion of combination chemotherapy. Patients receive G-CSF SQ beginning on day 0 and continuing until 3 days after blood counts have recovered. Sites of pretransplantation metastases greater than 3 cm are irradiated beginning after transplantation and after blood counts recover.

Patients are followed every month for 1 year.

PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study.

Ages Eligible for Study:  up to  65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven previously treated stage III or IV breast cancer
• No CNS disease
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• See Disease Characteristics

--Patient Characteristics--

• Age: Physiologic 65 and under
• Menopausal status: Not specified
• Performance status: ECOG 0 or 1
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Hepatic function normal unless due to liver metastases; Bilirubin less than 1.5 times normal; SGOT or SGPT less than 1.5 times normal; Alkaline phosphatase less than 1.5 times normal; If hepatitis C antibody positive, then liver function must be normal OR liver dysfunction must be due to metastatic disease and not chronic hepatitis
• Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance greater than 50 mL/min
• Cardiovascular: LVEF normal; No myocardial infarction within past 6 months; No significant arrhythmia requiring medications; No history of congestive heart failure
• Pulmonary: DLCO at least 50% predicted; FEV1 and/or FVC at least 75% predicted; No serious nonneoplastic pulmonary disease (severe chronic obstructive lung disease) that would preclude study therapy
• Other: Not pregnant; Negative pregnancy test HIV negative; Hepatitis B and C surface antigen negative; No active serious medical condition that would preclude study therapy

Illinois
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611,  United States

Study chairs or principal investigators

Jane N. Winter,  Study Chair,  Robert H. Lurie Cancer Center   

Study ID Numbers:  CDR0000067418; NU-92B3T; NCI-G99-1640
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004172
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08