Predicting Response to Capecitabine in Women With Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00953537
• Other study ID #: CDR0000638377
• Secondary ID: CALACASS-DPD-Sei
• Status: Completed
• Phase: N/A
• First received: August 5, 2009
• Last updated: February 8, 2015
• Start date: January 2009
• Est. completion date: February 2011

Study information

• Verified date: February 2015
• Source: Centre Antoine Lacassagne
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 303
• Est. completion date: February 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• capecitabine

Other:
• laboratory biomarker analysis

• pharmacological study

Locations

Country	Name	City	State
France	Centre Antoine Lacassagne	Nice

Sponsors (1)

Lead Sponsor	Collaborator
Centre Antoine Lacassagne

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Capecitabine-related toxicity (i.e., hematological, diarrhea, and hand-foot syndrome) recorded during the first and second courses		3 months	Yes