Predicting Response to Capecitabine in Women With Metastatic Breast Cancer

February 8, 2015 updated by: Centre Antoine Lacassagne

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

303

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Nice, France, 06189
        • Centre Antoine Lacassagne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: capecitabine
Other: pharmacological study
Other: laboratory biomarker analysis
Drug: capecitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Capecitabine-related toxicity (i.e., hematological, diarrhea, and hand-foot syndrome) recorded during the first and second courses
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Antoine Lacassagne

Investigators

  • Principal Investigator: Jean Marc Ferrero, MD, Centre Antoine Lacassagne

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Actual)

January 1, 2011

Study Completion (Actual)

February 1, 2011

Study Registration Dates

First Submitted

August 5, 2009

First Submitted That Met QC Criteria

August 5, 2009

First Posted (Estimate)

August 6, 2009

Study Record Updates

Last Update Posted (Estimate)

February 10, 2015

Last Update Submitted That Met QC Criteria

February 8, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000638377
  • 2008/21
  • CALACASS-DPD-Sein
  • INCA-RECF0942
  • EUDRACT-2008-004136-20

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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