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: Phase I/II trial to determine the effectiveness of combining capecitabine and paclitaxel in treating patients who have metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer	Drug: capecitabine  Drug: paclitaxel  Procedure: chemotherapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose (MTD) of capecitabine when combined with paclitaxel in patients with metastatic adenocarcinoma of the breast.
• Determine the clinical efficacy of the dose immediately preceding the MTD identified in phase I, in terms of response rate, time to treatment failure, time to disease progression, and overall survival, in these patients.
• Determine the toxicity of this regimen in these patients.
• Determine a well-tolerated drug combination for these patients.

OUTLINE: This is a dose-escalation, multicenter study of capecitabine.

Patients receive oral capecitabine twice daily on days 1-14 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 21 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 or more of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the dose level immediately preceding the MTD.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for phase I and 15-46 patients will be accrued for phase II of this study.

Ages Eligible for Study:  18 Years   -   64 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic adenocarcinoma of the breast
• Patients in phase I:
• Evaluable disease
• Patients in phase II:
• Bidimensionally measurable disease
• Bone metastases are not considered measurable
• No known or clinically suspected CNS metastases
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age:

• 18 to 64

Sex:

• Not specified

Menopausal status:

• Not specified

Performance status:

• WHO 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC greater than 3,500/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST/ALT no greater than 2 times ULN (3 times ULN if liver metastases present)

Renal:

• Patients in phase I:
• Creatinine clearance at least 50 mL/min
• Patients in phase I or II:
• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No grade 2 or greater atrioventricular block

Other:

• No cognitive impairment or severe psychiatric disorder
• No greater than grade 2 preexisting peripheral neuropathy
• No other prior or concurrent malignancy except adequately treated carcinoma in situ of the cervix or basal cell or squamous cell skin cancer
• Able to tolerate steroid premedication

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• More than 6 months since prior adjuvant chemotherapy
• At least 1 year since prior continuous infusion of fluorouracil or capecitabine
• At least 1 year since prior taxane administered once every 3 weeks
• No prior taxane or capecitabine administered weekly
• No more than 1 prior chemotherapy regimen for metastatic or locally advanced breast cancer
• No other concurrent chemotherapy

Endocrine therapy:

• Prior hormonal treatment for metastatic breast cancer allowed
• No concurrent continuous glucocorticosteroids
• No concurrent systemic endocrine treatment for breast cancer

Radiotherapy:

• No concurrent radiotherapy to indicator lesion or more than 30% of bone marrow

Surgery:

• Not specified

Other:

• No other concurrent anticancer treatment
• No concurrent immunosuppressive drugs
• Concurrent bisphosphonates allowed if indicator lesion is non-bone
• Able to tolerate steroid premedication

Switzerland
      Inselspital, Bern, Bern,  CH-3010,  Switzerland
      UniversitaetsSpital, Zurich,  CH-8091,  Switzerland

Study chairs or principal investigators

Stefan Aebi, MD,  Study Chair,  Inselspital, Bern   

Study ID Numbers:  CDR0000069236; SWS-SAKK-26/00; EU-20135; NCT00031876
Record last reviewed:  March 2005
Last Updated:  March 10, 2005
Record first received:  March 8, 2002
ClinicalTrials.gov Identifier:  NCT00031876
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08