NCT00953537

Predicting Response to Capecitabine in Women With Metastatic Breast Cancer

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 303 (actual)
• Sponsor: Centre Antoine Lacassagne · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	capecitabine
OTHER	laboratory biomarker analysis
OTHER	pharmacological study

Timeline

• Start date: 2009-01-01
• Primary completion: 2011-01-01
• Completion: 2011-02-01
• First posted: 2009-08-06
• Last updated: 2015-02-10

Locations

1 site across 1 country: France