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 plus 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: anastrozole  Drug: carboplatin  Drug: cisplatin  Drug: cyclophosphamide  Drug: docetaxel  Drug: doxorubicin  Drug: etoposide  Drug: filgrastim  Drug: pamidronate  Drug: thiotepa	Phase II

Further Study Details: 

OBJECTIVES: I. Assess the toxicity and response rates to induction therapy with docetaxel and doxorubicin in women with chemotherapy naive metastatic breast cancer.

II. Assess the toxicity and response rates to sequential high dose chemotherapy following induction chemotherapy in women with metastatic breast cancer.

III. Determine the hematopoietic recovery rate following CD34+ selected peripheral blood stem cell support in this patient population.

IV. Assess the toxicity of noncytotoxic maintenance therapy following high dose chemotherapy in this patient population.

PROTOCOL OUTLINE: This is a multicenter study.

Patients with no prior chemotherapy for metastatic disease receive induction chemotherapy consisting of doxorubicin IV immediately followed by docetaxel IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) subcutaneously (SQ) beginning on day 2 and continuing until day 11-15. Induction therapy repeats every 3 weeks for 4 courses.

Within 4 weeks of the last course of induction chemotherapy, patients receive mobilization chemotherapy consisting of cyclophosphamide IV for 2 days, and etoposide IV and cisplatin IV for 3 days. At 24 hours following completion of chemotherapy, patients receive G-CSF SQ twice daily until the target number of peripheral blood stem cells (PBSC) are reached.

Within 5 weeks following completion of mobilization chemotherapy, patients receive cyclophosphamide IV, thiotepa IV, and carboplatin IV continuously on days -7 through -4. Patients receive CD34+ selected PBSC on day 0 followed 4 hours later by G-CSF SQ daily and continuing until blood counts recover.

Within 30 days of blood count recovery or immediately following completion of post transplantation radiotherapy, patients receive maintenance therapy consisting of oral anastrozole daily until disease progression. Patients with bone involvement also receive pamidronate IV over 2 hours monthly for 1 year.

Patients are followed monthly for 6 months, every 3 months for 1 year, every 4-6 months for 5 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study over 12 months.

Ages Eligible for Study:  18 Years   -   65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed epithelial carcinoma of the breast; Metastatic disease including ipsilateral supraclavicular lymph nodes and the chest wall (no axillary nodes)
• Measurable or evaluable (bone only) disease on exam or radiography
• No apocrine, adenocystic, squamous cell carcinoma, sarcoma, or lymphoma
• No symptomatic CNS disease or clinical evidence of CNS metastases
• Surgically accessible disease
• Hormone receptor status: Progesterone or estrogen receptor status known

--Prior/Concurrent Therapy--

• At least 6 months since prior adjuvant therapy
• Biologic therapy: Not specified
• Chemotherapy: No more than 2 courses of prior induction docetaxel and doxorubicin allowed if staged within 4 weeks of chemotherapy initiation; No prior cumulative adjuvant doxorubicin dose greater than 360 mg/m2; No other prior chemotherapy for metastatic disease
• Endocrine therapy: Prior hormonal therapy for metastatic disease allowed
• Radiotherapy: Not specified
• Surgery: See Disease Characteristics

--Patient Characteristics--

• Age: 18 to 65
• Menopausal status: Not specified
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: WBC greater than 3,000/mm3; Platelet count greater than 100,000/mm3
• Hepatic: Bilirubin less than 3.0 mg/dL; SGOT no greater than 6 times upper limit of normal
• Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance greater than 50 mL/min
• Cardiovascular: Ejection fraction at least 40% by MUGA scan; No angina pectoris requiring active nitrate therapy; No myocardial infarction within the past 6 months; No uncontrolled congestive heart failure; No uncontrolled hypertension; No major ventricular arrhythmia
• Other: No uncompensated endocrine dysfunction; HIV negative; Hepatitis B negative (core antigen negative if vaccinated); No other prior malignancy within the past 5 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix; No active infection or other medical condition that would preclude study; Not pregnant; Negative pregnancy test; Fertile patients must use effective contraception

Illinois
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611,  United States
New Jersey
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
Ohio
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States
Pennsylvania
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104,  United States

Study chairs or principal investigators

Andrew Louis Pecora,  Study Chair,  Robert H. Lurie Cancer Center   

Study ID Numbers:  CDR0000067586; NU-H97B1; NCI-G00-1682
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  March 7, 2000
ClinicalTrials.gov Identifier:  NCT00004906
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08