RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by autologous peripheral stem cell transplantation in treating women who have metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer	Drug: etoposide  Drug: ifosfamide  Drug: topotecan	Phase II

Further Study Details: 

OBJECTIVES: I. Evaluate the efficacy and toxicity of high dose topotecan with ifosfamide and etoposide followed by autologous peripheral blood stem cell rescue in women with metastatic breast cancer. II. Evaluate the response rates, progression free survival, engraftment, and nonrelapse related mortality in women treated with this regimen. III. Evaluate the pharmacokinetic profile of high dose topotecan with respect to the efficacy and toxicity of ifosfamide and etoposide in these women.

PROTOCOL OUTLINE: Peripheral blood stem cells (PBSC) are harvested from the patient and stored. Patients receive ifosfamide IV over 2 hours and topotecan IV over 30 minutes on days -8 to -6, and etoposide IV daily over 24 hours on days -5 to -3. Autologous PBSC are reinfused on day 0. Patients are followed at 1, 3, 6, and 12 months, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study over 2 years.

Ages Eligible for Study:  18 Years   -   64 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed metastatic breast cancer that has demonstrated at least partial response to any salvage regimen; Partial response defined as at least 50% reduction in measurable or evaluable disease for at least 4 weeks, no disease progression, no new lesions, or bone lesions that remain static for at least 8 weeks with an improvement in pain symptoms; No more than 3 organs involved with metastatic disease
• No prior or active CNS involvement
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: See Disease Characteristics; No more than 2 prior salvage regimens for metastatic disease; No prior topotecan
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Not specified
• Other: No concurrent nitroglycerin preparations for angina; No concurrent antiarrhythmics for major ventricular arrhythmias

--Patient Characteristics--

• Age: 18 to 64
• Sex: Female
• Menopausal status: Not specified
• Performance status: ECOG 0-1
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin no greater than 2.0 mg/dL; SGOT or SGPT no greater than 2.5 times upper limit of normal; No history of severe hepatic dysfunction
• Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance at least 60 mL/min
• Cardiovascular: No severe cardiac dysfunction; Ejection fraction at least 50% by MUGA; No major heart disease; Controlled hypertension allowed
• Pulmonary: DLCO at least 50% of normal OR No symptomatic obstructive or restrictive disease
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective barrier contraception; No uncontrolled insulin dependent diabetes mellitus; No uncompensated major thyroid or adrenal dysfunction; No significant skin breakdown from tumor or other disease; No other prior malignancy in past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix; No active infections; HIV negative

Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States

Study chairs or principal investigators

Karen K. Fields,  Study Chair,  H. Lee Moffitt Cancer Center and Research Institute   

Study ID Numbers:  CDR0000068045; MCC-12220; NCI-G00-1809; MCC-IRB-5699
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  July 5, 2000
ClinicalTrials.gov Identifier:  NCT00006032
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08