High Throughput Technologies to Drive Breast Cancer Patients to Specific Phase I/II Trials of Targeted Agents (SAFIR-01)

This study has been completed.
Sponsor:
Collaborators:
Ministry of Health, France
Gustave Roussy, Cancer Campus, Grand Paris
Information provided by (Responsible Party):
UNICANCER
ClinicalTrials.gov Identifier:
NCT01414933
First received: June 17, 2011
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

High sensitivity to targeted agents has been observed in patients whose tumor cells present a genetic/genomic deregulation of the target (Kit mutation, ERBB2 amplification, EGFR mutations) together with addiction to the given target. More recently, activation of "alternative pathways" (Kras mutation, PI3K mutations) have been reported as a common resistance mechanism to single agent tyrosine kinase inhibitors (trastuzumab, cetuximab).

From these data has emerged the hypothesis that identification of the deregulated pathway through new molecular tools could allow to propose a more tailored targeted regimen.

Based on these concepts, numbers of phase I/II trials enrich their populations in patients presenting specific molecular alterations.

High throughput technologies (array CGH, sequencing, gene expression array) identify deregulated genes. In addition, these technologies determine whether such genomic alterations are single (expected efficacy of single agent) or multiple (rationale for combination). In a pilot study that included 135 patients, we recently performed a combination of array CGH and hot spot mutation array in order to drive patients into phase I/II clinical trials. This study led to the conclusions that high throughput technologies i. are feasible (80%) and robust, ii. identify "targetable" genomic alterations in around 40% of samples.

In the present study, the investigators will perform high throughput technologies to drive 400 metastatic breast cancer patients into specific phase I/II trials.


Condition Intervention
Metastatic Breast Cancer
Other: Biopsy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: High Throughput Technologies to Drive Breast Cancer Patients to Specific Phase I/II Trials of Targeted Agents

Resource links provided by NLM:


Further study details as provided by UNICANCER:

Primary Outcome Measures:
  • number of patients included in early phase trials evaluating targeted drugs [ Time Frame: one year after obtaining the molecular profile ] [ Designated as safety issue: No ]
    To use whole genome / integrated biology approach to drive patients in early clinical trials. The goal is to include at least 30% of the patients in a clinical trial evaluating targeted agent, according to the molecular alteration detected on high throughput technologies


Secondary Outcome Measures:
  • overall survival [ Time Frame: 3 years after inclusion in SAFIR ] [ Designated as safety issue: No ]
    To evaluate the efficacy of such patient selection in terms of survival

  • Progression free survival [ Time Frame: 3 years after inclusion in SAFIR ] [ Designated as safety issue: No ]
    To evaluate the efficacy of such patient selection in terms of progression free survival

  • To evaluate the efficacy of such patient selection in terms of survival response rate [ Time Frame: 3 years after inclusion in SAFIR ] [ Designated as safety issue: No ]
    To evaluate the efficacy of such patient selection in terms of best response rate


Biospecimen Retention:   Samples With DNA

Metastasis biopsy and DNA from biopsy


Enrollment: 423
Study Start Date: May 2011
Study Completion Date: May 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Other: Biopsy
    Breast metastases biopsy
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

women or men with metastatic breast cancer

Criteria

Inclusion Criteria:

  • Men and Women with histologically diagnosed breast cancer
  • Metastatic relapse or stage IV breast cancer at diagnosis
  • Metastases amenable to biopsy
  • Age <70 years old
  • PS 0/1
  • No restriction regarding the number of previous chemotherapy or endocrine therapies

Exclusion Criteria:

  • Age <18
  • Life expectancy <3 months
  • Symptomatic or progressing brain metastases
  • Progressive patients at the time of biopsy
  • LVEF <50% (MUGA or ultrasonography)
  • Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:

    • Absolute neutrophil count < 1.5 x 109/L
    • Platelet count < 100 x 109/L
    • Haemoglobin < 90 g/L
    • ASAT/ALAT > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases
    • Total bilirubin > 1.5 times ULN
    • Creatinine >1.5 times ULN
    • Corrected calcium > ULN
    • Phosphate > ULN
  • Abnormal blood coagulation that contra-indicates biopsy
  • Patients deprived of liberty or placed under the authority of a tutor
  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: NCT01414933

Locations
France
Institut Bergonié
Bordeaux, France
Centre François Baclesse
Caen, France
Centre Georges François Leclerc
Dijon, France
Centre Oscar Lambret
Lille, France
Centre Léon Bérard
Lyon, France
Institut Paoli Calmettes
Marseille, France
Centre Val D'Aurelle
Montpellier, France
Centre Alexis Vautrin
Nancy, France
Institut de Cancérologie de l'Ouest/ René Gauducheau
Nantes, France
Centre Antoine Lacassagne
Nice, France
Institut Curie
Paris, France
Institut Jean Godinot
Reims, France
Centre Eugène Marquis
Rennes, France
Centre Henri Becquerel
Rouen, France
Institut Curie/ René Huguenin
Saint-Cloud, France
Centre Paul Strauss
Strasbourg, France
Institut Claudius Regaud
Toulouse, France
Institut Gustave Roussy
Villejuif, France
Sponsors and Collaborators
UNICANCER
Ministry of Health, France
Gustave Roussy, Cancer Campus, Grand Paris
Investigators
Principal Investigator: Fabrice André, MD phD Institut Gustave Roussy, Villejuif, France
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT01414933     History of Changes
Other Study ID Numbers: GRT01/0710 SAFIR-01
Study First Received: June 17, 2011
Last Updated: January 10, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on August 28, 2014