High Throughput Technologies to Drive Breast Cancer Patients to Specific Phase I/II Trials of Targeted Agents (SAFIR-01)
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.
|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|
- 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
- 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
|Study Start Date:||May 2011|
|Study Completion Date:||May 2013|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01414933
|Centre François Baclesse|
|Centre Georges François Leclerc|
|Centre Oscar Lambret|
|Centre Léon Bérard|
|Institut Paoli Calmettes|
|Centre Val D'Aurelle|
|Centre Alexis Vautrin|
|Institut de Cancérologie de l'Ouest/ René Gauducheau|
|Centre Antoine Lacassagne|
|Institut Jean Godinot|
|Centre Eugène Marquis|
|Centre Henri Becquerel|
|Institut Curie/ René Huguenin|
|Centre Paul Strauss|
|Institut Claudius Regaud|
|Institut Gustave Roussy|
|Principal Investigator:||Fabrice André, MD phD||Institut Gustave Roussy, Villejuif, France|