Predicting Response to Capecitabine in Women With Metastatic Breast Cancer
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.
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multicentric Pilot Study of Dihydropyrimidine Dehydrogenase (DPD) Deficiency for Predicting Capecitabine Toxicity in Breast Cancer Patients|
- Capecitabine-related toxicity (i.e., hematological, diarrhea, and hand-foot syndrome) recorded during the first and second courses [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2009|
|Study Completion Date:||February 2011|
|Primary Completion Date:||January 2011 (Final data collection date for primary outcome measure)|
|capecitabine||Drug: capecitabine Other: laboratory biomarker analysis Other: pharmacological study|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00953537
|Centre Antoine Lacassagne|
|Nice, France, 06189|
|Principal Investigator:||Jean Marc Ferrero, MD||Centre Antoine Lacassagne|