Clinical trial NCT01414933: High Throughput Technologies to Drive Breast Cancer Patients to Specific Phase I/II Trials of Targeted Agents
Official title: High Throughput Technologies to Drive Breast Cancer Patients to Specific Phase I/II Trials of Targeted Agents
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Metastatic Breast Cancer
Lead sponsor: UNICANCER
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: Gustave Roussy, Cancer Campus, Grand Paris
First posted: 2011-08-11
Enrollment: 423
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: women or men with metastatic breast cancer

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: number of patients included in early phase trials evaluating targeted drugs
timeFrame: one year after obtaining the molecular profile
Secondary outcomes:
measure: overall survival
timeFrame: 3 years after inclusion in SAFIR
measure: Progression free survival
timeFrame: 3 years after inclusion in SAFIR
measure: To evaluate the efficacy of such patient selection in terms of survival response rate
timeFrame: 3 years after inclusion in SAFIR
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonié
city: Caen
country: France
facility: Centre François Baclesse
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Centre Val D'Aurelle
city: Nancy
country: France
facility: Centre Alexis Vautrin
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest/ René Gauducheau
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie
city: Reims
country: France
facility: Institut Jean Godinot
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Cloud
country: France
facility: Institut Curie/ René Huguenin
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Institut Gustave Roussy, Villejuif, France
name: Fabrice André, MD phD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Andre F, Delaloge S, Soria JC. Biology-driven phase II trials: what is the optimal model for molecular selection? J Clin Oncol. 2011 Apr 1;29(10):1236-8. doi: 10.1200/JCO.2010.31.6877. Epub 2011 Feb 22. No abstract available.
citation: Andre F, Bachelot T, Commo F, Campone M, Arnedos M, Dieras V, Lacroix-Triki M, Lacroix L, Cohen P, Gentien D, Adelaide J, Dalenc F, Goncalves A, Levy C, Ferrero JM, Bonneterre J, Lefeuvre C, Jimenez M, Filleron T, Bonnefoi H. Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER). Lancet Oncol. 2014 Mar;15(3):267-74. doi: 10.1016/S1470-2045(13)70611-9. Epub 2014 Feb 7.