Predicting Response to Capecitabine in Women With Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Centre Antoine Lacassagne
ClinicalTrials.gov Identifier:
NCT00953537
First received: August 5, 2009
Last updated: February 8, 2015
Last verified: February 2015
  Purpose

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.


Condition Intervention
Breast Cancer
Drug: capecitabine
Other: laboratory biomarker analysis
Other: pharmacological study

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicentric Pilot Study of Dihydropyrimidine Dehydrogenase (DPD) Deficiency for Predicting Capecitabine Toxicity in Breast Cancer Patients

Resource links provided by NLM:


Further study details as provided by Centre Antoine Lacassagne:

Primary Outcome Measures:
  • Capecitabine-related toxicity (i.e., hematological, diarrhea, and hand-foot syndrome) recorded during the first and second courses [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Enrollment: 303
Study Start Date: January 2009
Study Completion Date: February 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
capecitabine Drug: capecitabine Other: laboratory biomarker analysis Other: pharmacological study

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00953537

Locations
France
Centre Antoine Lacassagne
Nice, France, 06189
Sponsors and Collaborators
Centre Antoine Lacassagne
Investigators
Principal Investigator: Jean Marc Ferrero, MD Centre Antoine Lacassagne
  More Information

Additional Information:
No publications provided

Responsible Party: Centre Antoine Lacassagne
ClinicalTrials.gov Identifier: NCT00953537     History of Changes
Other Study ID Numbers: CDR0000638377, CALACASS-DPD-Sein, 2008/21, INCA-RECF0942, EUDRACT-2008-004136-20
Study First Received: August 5, 2009
Last Updated: February 8, 2015
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Centre Antoine Lacassagne:
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Capecitabine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 25, 2015