Predicting Response to Capecitabine in Women With Metastatic Breast Cancer

NCT ID: NCT00953537

Last Updated: 2015-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 303 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2011-02-28

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

capecitabine

Group Type: OTHER

capecitabine

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Interventions

capecitabine

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Centre Antoine Lacassagne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean Marc Ferrero, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Antoine Lacassagne

Locations

Centre Antoine Lacassagne

Nice, , France

Countries

France

Other Identifiers

CALACASS-DPD-Sein

Identifier Type: -

Identifier Source: secondary_id

2008/21

Identifier Type: -

Identifier Source: secondary_id

INCA-RECF0942

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2008-004136-20

Identifier Type: -

Identifier Source: secondary_id

CDR0000638377

Identifier Type: -

Identifier Source: org_study_id