Predicting Response to Capecitabine in Women With Metastatic Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT00953537
- Lead Sponsor
- Centre Antoine Lacassagne
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 303
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description capecitabine pharmacological study - capecitabine laboratory biomarker analysis - capecitabine capecitabine -
- Primary Outcome Measures
Name Time Method Capecitabine-related toxicity (i.e., hematological, diarrhea, and hand-foot syndrome) recorded during the first and second courses 3 months
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Centre Antoine Lacassagne
🇫🇷Nice, France