Irinotecan and Capecitabine in Treating Women With Advanced Breast Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as irinotecan and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Irinotecan may help capecitabine kill more tumor cells by making tumor cells more sensitive to the drug. PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan and capecitabine in treating women with advanced breast cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the maximum tolerated dose of capecitabine and irinotecan in women with advanced breast cancer. Determine the degree of accumulation of cells in S-phase in tumor biopsies from patients treated with this regimen. Determine the dose-limiting toxicity and other major or unusual toxic effects of this regimen in these patients. Determine any antitumor activity of this regimen in these patients. Determine the pharmacokinetics of this regimen, including the active metabolite SN-38, in these patients. Correlate pharmacokinetic parameters of this regimen with the biological changes observed in these patients. Determine, preliminarily, the relationship of tumor response with modulation of S-phase in patients treated with this regimen. OUTLINE: This is a dose-escalation study. Patients receive irinotecan IV over 1.5 hours on days 1, 8, 22, and 29 and oral capecitabine twice daily on days 1-14 and 23-36. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: A total of 8-37 patients will be accrued for this study within 18-24 months.

Official Title
-----------------
Phase I Study of Irinotecan Followed by Capecitabine in Patients With Advanced Breast Carcinoma

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: capecitabine
* Drug: irinotecan hydrochloride


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Diagnosis of breast cancer not eligible for potentially curative therapy or studies of higher priority Advanced disease Tumor accessible to biopsy AND not irradiated Failed at least 1 prior chemotherapy regimen (not including adjuvant chemotherapy) Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Female Menopausal status Not specified Performance status ECOG 0-2 Life expectancy At least 3 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.0 g/dL Hepatic AST ≤ 2 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN Renal Creatinine ≤ 1.5 times ULN OR Creatinine clearance ≥ 50 mL/min Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No active uncontrolled bacterial, viral, or fungal infection No poor medical risk from non-malignant systemic disease PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics Prior irinotecan allowed Prior carboplatin allowed More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) Endocrine therapy Not specified Radiotherapy See Disease Characteristics More than 4 weeks since prior radiotherapy except for small port radiotherapy for local control Surgery More than 4 weeks since prior major surgery Other No concurrent high-dose IV cyclosporine

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: capecitabine|nan|
|Drug: irinotecan hydrochloride|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent breast cancer, stage IV breast cancer