Breast Cancer
Conditions
Keywords
stage IV breast cancer
Brief summary
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
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.
Interventions
DRUGcapecitabine
OTHERlaboratory biomarker analysis
OTHERpharmacological study
Sponsors
Centre Antoine Lacassagne
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Capecitabine-related toxicity (i.e., hematological, diarrhea, and hand-foot syndrome) recorded during the first and second courses | 3 months |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORJean Marc Ferrero, MD
Centre Antoine Lacassagne
Outcome results
None listed