High Throughput Technologies to Drive Breast Cancer Patients to Specific Phase I/II Trials of Targeted Agents

NCT ID: NCT01414933

Last Updated: 2017-05-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 423 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2013-05-31

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.

Conditions

Metastatic Breast Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Biopsy

Breast metastases biopsy

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role: collaborator

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fabrice André, MD phD

Role: PRINCIPAL_INVESTIGATOR

Institut Gustave Roussy, Villejuif, France

Locations

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

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 21343554 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24508104 (View on PubMed)

Other Identifiers

GRT01/0710 SAFIR-01

Identifier Type: -

Identifier Source: org_study_id