Predicting Response to Capecitabine in Women With Metastatic Breast Cancer

Centre Antoine Lacassagne

Status: Completed

Conditions: Breast Cancer

Treatments: Drug: capecitabine; Other: laboratory biomarker analysis; Other: pharmacological study

Study type: Interventional

Funder types: Other

Identifiers

NCT00953537

EUDRACT-2008-004136-20

2008/21

INCA-RECF0942

CALACASS-DPD-Sein

CDR0000638377

Details and patient eligibility

About

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.

Full 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.

Enrollment: 303 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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303 participants in 1 patient group

capecitabine

Other group

Treatment:

Other: pharmacological study

Drug: capecitabine

Other: laboratory biomarker analysis