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

NCT01414933 | Completed DMC

• 1 other identifier: GRT01/0710 SAFIR-01
• Study Type: observational
• Target: 423
• Locations: 1 country
• Sites: 18

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

Outcome Measures

Primary Outcomes (1)

• number of patients included in early phase trials evaluating targeted drugs

  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

  one year after obtaining the molecular profile

Secondary Outcomes (3)

• overall survival

  3 years after inclusion in SAFIR

• Progression free survival

  3 years after inclusion in SAFIR

• To evaluate the efficacy of such patient selection in terms of survival response rate

  3 years after inclusion in SAFIR

Interventions

Biopsy OTHER

Breast metastases biopsy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

women or men with metastatic breast cancer

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UNICANCER: lead
• Ministry of Health, France: collaborator
• Gustave Roussy, Cancer Campus, Grand Paris: collaborator

Study Sites (18)

Institut Bergonié

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Centre Georges François Leclerc

Dijon, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Centre Val D'Aurelle

Montpellier, France

Location

Centre Alexis Vautrin

Nancy, France

Location

Institut de Cancérologie de l'Ouest/ René Gauducheau

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Institut Curie

Paris, France

Location

Institut Jean Godinot

Reims, France

Location

Centre Eugène Marquis

Rennes, France

Location

Centre Henri Becquerel

Rouen, France

Location

Institut Curie/ René Huguenin

Saint-Cloud, France

Location

Centre Paul Strauss

Strasbourg, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Related Publications (2)

• 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.

  PMID: 21343554 BACKGROUND

• 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.

  PMID: 24508104 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Metastasis biopsy and DNA from biopsy

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Biopsy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Fabrice André, MD phD

  Institut Gustave Roussy, Villejuif, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2011
• First Posted: August 11, 2011
• Study Start: May 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: May 1, 2013
• Last Updated: May 4, 2017

Record last verified: 2017-05

Locations

FR (18)