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

Metastatic Breast Cancer Clinical Trial

— SAFIR-01  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01414933
• Other study ID #: GRT01/0710 SAFIR-01
• Status: Completed
• Phase: N/A
• First received: June 17, 2011
• Last updated: May 3, 2017
• Start date: May 2011
• Est. completion date: May 2013

Study information

• Verified date: May 2017
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 423
• Est. completion date: May 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Other:
• Biopsy
Breast metastases biopsy

Locations

Country	Name	City	State
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

Sponsors (3)

Lead Sponsor	Collaborator
UNICANCER	Gustave Roussy, Cancer Campus, Grand Paris, Ministry of Health, France

Country where clinical trial is conducted

France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	overall survival	To evaluate the efficacy of such patient selection in terms of survival	3 years after inclusion in SAFIR
Secondary	Progression free survival	To evaluate the efficacy of such patient selection in terms of progression free survival	3 years after inclusion in SAFIR
Secondary	To evaluate the efficacy of such patient selection in terms of survival response rate	To evaluate the efficacy of such patient selection in terms of best response rate	3 years after inclusion in SAFIR