Predicting Response to Capecitabine in Women With Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Identifying genes that increase a person's susceptibility to side effects caused by capecitabine may help doctors plan better treatment. PURPOSE: This clinical trial is studying blood samples in predicting response to capecitabine in women with metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary To determine the sensitivity, specificity, and positive and negative predictive values of dihydrouracil/uracil (UH_2/U) ratio measured before starting treatment on grade 3-4 capecitabine-related toxicity in women with metastatic breast cancer. Secondary To prospectively test the value of the germinal genotype of thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) as predictors of resistance to capecitabine. To evaluate the practical feasibility of such pre-therapeutic screening. To determine the sensitivity, specificity, and positive and negative predictive values of dihydropyrimidine dehydrogenase genotyping on grade 3-4 capecitabine-related toxicity in the first and second courses. To evaluate the predictive gain provided by genotyping relative to phenotyping alone. To evaluate the influence of TS and MTHFR gene polymorphisms on clinical response and duration of response. To evaluate the pharmacokinetics of capecitabine and its metabolites and their relationship with UH_2/U and genotype. To evaluate the total cost of pre-therapeutic phenotyping alone and the combination of phenotyping and genotyping. To exhaustively analyze the 23 exons of the dihydropyrimidine dehydrogenase (DPYD) gene in patients who developed toxicity. OUTLINE: This is a multicenter study. Patients receive oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected 8-15 days before the start of treatment and periodically on the first day of treatment for dihydropyrimidine dehydrogenase phenotyping (dihydrouracil/uracil ratio and high performance liquid chromatography analysis), genotyping (4 most relevant single nucleotide polymorphisms), and pharmacokinetic analysis.

Official Title
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Multicentric Pilot Study of Dihydropyrimidine Dehydrogenase (DPD) Deficiency for Predicting Capecitabine Toxicity in Breast Cancer Patients

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: capecitabine
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Radiologically (by scintography) or histologically confirmed metastatic breast cancer At least 1 measurable or evaluable target lesion Receiving capecitabine as monotherapy or with targeted antiangiogenic therapies (e.g., bevacizumab or trastuzumab) No uncontrolled brain metastases Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified Life expectancy ≥ 3 months Fertile patients must use effective contraception No chronic uncontrolled illness No congestive heart failure No peripheral venous disease No severe uncontrolled infection No hypoxemic respiratory failure No prior primary cancer except for basal cell carcinoma of the skin No psychologic disorder PRIOR CONCURRENT THERAPY: See Disease Characteristics No capecitabine co-administered with chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: capecitabine<br> | Drug: capecitabine<br> <br> Other: laboratory biomarker analysis<br> <br> Other: pharmacological study<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Capecitabine-related toxicity (i.e., hematological, diarrhea, and hand-foot syndrome) recorded during the first and second courses |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer