RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells, allowing higher doses of chemotherapy to be used.

PURPOSE: Phase I/II trial to study the effectiveness of paclitaxel added to a regimen of high-dose chemotherapy with cyclophosphamide and carboplatin followed by peripheral stem cell transplantation in treating women with metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer	Drug: carboplatin  Drug: cyclophosphamide  Drug: filgrastim  Drug: mesna  Drug: paclitaxel	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Estimate the maximum tolerated dose of paclitaxel in combination with high-dose carboplatin/cyclophosphamide followed by autologous peripheral blood stem cell support in women with stage IV breast cancer.

II. Assess the nonhematologic toxic effects associated with this combination.

III. Assess the response rate, duration of response, and survival in chemotherapy-sensitive women with metastatic breast cancer treated with this regimen.

PROTOCOL OUTLINE: This is a dose-finding study. All patients undergo collection of peripheral blood stem cells (PBSC) with granulocyte colony-stimulating factor (G-CSF) mobilization prior to high-dose chemotherapy.

Cohorts of 3-5 patients are treated at successively higher dose levels of paclitaxel until a maximum tolerated dose (MTD) is found. Paclitaxel is given as a single 24-hour infusion, followed by fixed doses of high-dose cyclophosphamide for 2 days, then carboplatin for 4 days. Three days later, patients receive PBSC and G-CSF for hematopoietic reconstitution. Additional patients are entered at the MTD.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, and every 4-6 months thereafter.

PROJECTED ACCRUAL: 50 patients will be accrued. The study is expected to take 18 months.

Ages Eligible for Study:  18 Years   -   65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically diagnosed, stage IV adenocarcinoma of the breast
• Previously untreated or prior adjuvant chemotherapy only; CR or PR following 3-5 courses of induction chemotherapy for current diagnosis with one of the following: Cyclophosphamide/doxorubicin; Cyclophosphamide/methotrexate/fluorouracil; Cyclophosphamide/mitoxantrone
• No active CNS metastases on CT or MRI
• Hormone receptor status: Any status

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: Hematologically recovered from prior chemotherapy
• Endocrine therapy: Failure on 1 prior hormonal regimen required for ER-positive disease (greater than 10 femtomoles) unless visceral metastatic crisis requires immediate chemotherapy
• Radiotherapy: Not specified
• Surgery: Not specified

--Patient Characteristics--

• Age: 18 to 65
• Sex: Women
• Menopausal status: Pre- or postmenopausal
• Performance status: ECOG 0-2
• Hematopoietic: WBC greater than 3,000; Platelets greater than 100,000
• Hepatic: Bilirubin no greater than 2.0 mg/dL
• Renal: Creatinine clearance greater than 60 mL/min
• Cardiovascular: Left ventricular ejection fraction greater than 50% on MUGA or echocardiogram; No abnormal cardiac conduction on EKG, i.e.: No second- or third-degree heart block; No bundle-branch block; No arrhythmia except: Supraventricular sinus tachycardia; Occasional premature atrial or ventricular contractions
• Pulmonary: DLCO greater than 60% of predicted
• Other: No preexisting peripheral neuropathy; No HIV antibody; No history of second malignancy within 5 years except: Nonmelanomatous skin cancer; Cervical carcinoma in situ; No pregnant or nursing women

Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5265,  United States
Missouri
      St. Louis University Health Sciences Center, Saint Louis,  Missouri,  63110-0250,  United States
Tennessee
      Methodist Hospital-Central Unit, Memphis,  Tennessee,  38104,  United States

Study chairs or principal investigators

Paul J. Petruska,  Study Chair,  St. Louis University   

Study ID Numbers:  CDR0000064017; SLUMC-7915; NCI-V95-0608
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002628
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08