Predicting Response to Capecitabine in Women With Metastatic Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00953537
First received: August 5, 2009
Last updated: NA
Last verified: August 2009
History: No changes posted
  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
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 National Cancer Institute (NCI):

Primary Outcome Measures:
  • Capecitabine-related toxicity (i.e., hematological, diarrhea, and hand-foot syndrome) recorded during the first and second courses [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: January 2009
Estimated Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
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 Recruiting
Nice, France, 06189
Contact: Jean Marc Ferrero, MD    33-4-9203-1114    jean-marc.ferrerero@nice.fnclcc.fr   
Sponsors and Collaborators
Centre Antoine Lacassagne
Investigators
Principal Investigator: Jean Marc Ferrero, MD Centre Antoine Lacassagne
  More Information

Additional Information:
No publications provided

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: August 5, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IV breast cancer

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

ClinicalTrials.gov processed this record on September 18, 2014