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.

PURPOSE: Randomized phase II trial to compare the effectiveness of paclitaxel with or without PSC 833 in treating patients with metastatic breast cancer.

Condition	Treatment or Intervention	Phase
recurrent breast cancer	Drug: paclitaxel  Drug: PSC 833	Phase II

Further Study Details: 

OBJECTIVES: I. Evaluate the response rate and time to treatment failure of paclitaxel with and without the P-glycoprotein (Pgp) antagonist PSC 833 in advanced breast cancer.

II. For each treatment arm, relate paclitaxel AUC (area under curve), and/or time above .05 um/L, to myelosuppression and/or response.

III. To obtain preliminary estimates of MDR in this group of patients by measuring MDR1-Pgp immunostaining in pretreatment biopsies in 20 patients and biopsies taken at the time of progression.

PROTOCOL OUTLINE: This is a randomized study.

Patients are stratified according to three criteria: 1) treatment within 2 years of adjuvant chemotherapy vs. progression on chemotherapy for advanced disease 2) measurable vs. evaluable disease 3) institution.

Patients receive paclitaxel alone or paclitaxel plus PSC 833.

In the first arm, paclitaxel alone is administered by continuous infusion over 3 hours once every 3 weeks.

In the second arm, PSC 833 is administered PO four times a day for 3 days; paclitaxel is administered by continuous infusion over 3 hours on day 2. Courses repeat every 3 weeks.

PROJECTED ACCRUAL: Approximately 70 patients will be accrued per year in this study.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Metastatic breast cancer within 2 years of an adjuvant anthracycline based chemotherapy for advanced disease, or failure of one prior anthracycline based chemotherapeutic regimen for advanced breast cancer; Exception: When anthracyclines are contraindicated, metastatic disease within 2 years of any adjuvant cytotoxic regimen, or failure of one prior cytotoxic chemotherapeutic regimen for advanced breast cancer also qualifies
• Evaluable or measurable disease in at least one nonirradiated area
• No CNS metastases

--Prior/Concurrent Therapy--

• At least 4 weeks since any investigational therapy
• Biologic therapy: No concurrent antibiotics, e.g. clarithromycin, erythromycin, nafcillin, rifampin, itraconazole, ketoconazole, or fluconazole (no greater than 200 mg/day allowed)
• Chemotherapy: No prior paclitaxel; At least 6 weeks since nitrosoureas; At least 4 weeks since other myelosuppressive chemotherapy
• Endocrine therapy: At least 2 weeks since hormone therapy; No concurrent danazol
• Radiotherapy: At least 3 weeks since radiation therapy
• Surgery: Must be recovered from previous surgery
• Other: No concurrent calcium channel blockers, e.g. diltiazem, nicardipine, and verapamil; No concurrent anticonvulsants, e.g. carbamazepine, phenobarbital, and phenytoin; No concurrent bromocriptine

--Patient Characteristics--

• Age: Not specified
• Performance status: SWOG 0-2
• Life expectancy: Not specified
• Hematopoietic: Platelet count at least 100,000/mm3; Hemoglobin at least 8.0 g/dL; Absolute neutrophil count at least 1500/mm3
• Hepatic: Total serum bilirubin no greater than 1.5 mg/dL; No history of chronic active hepatitis or cirrhosis; SGOT and/or SGPT no greater than 2 times the upper limit of normal
• Renal: Serum creatinine no greater than 2.0 mg/dL
• Other: Not HIV positive; Not pregnant or nursing; Effective contraceptive required of fertile patients; No uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or bowel obstruction; No history of a second malignancy with the exception of non-melanoma skin cancer or carcinoma in situ of the cervix; No known hypersensitivity to ingredients of the study medication or cyclosporine; No neurologic problems requiring treatment; No treatment with drugs within 48 hours that are known to interact with cyclosporine

California
      Beckman Research Institute, City of Hope, Duarte,  California,  91010,  United States
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States
      USC/Norris Comprehensive Cancer Center, Los Angeles,  California,  90033-0800,  United States
Canada, Ontario
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada

Study chairs or principal investigators

James H. Doroshow,  Study Chair,  Beckman Research Institute   

Study ID Numbers:  CDR0000065380; CHNMC-96002; NCI-H97-1137
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002937
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08