A Study to Select Rational Therapeutics Based on the Analysis of Matched Tumor and Normal Biopsies in Subjects With Advanced Malignancies

NCT01856296 | Completed

• 2 other identifiers: 2012-A01738-352012/1946
• Study Type: interventional
• Target: 303
• Locations: 1 country
• Sites: 1

Brief Summary

An open non-randomized study using biology driven selection of therapies. WINTHER study will explore matched tumoral and normal tissue biopsies and will use a novel method for predicting efficacy of drugs. The aim is to provide a rational personalized therapeutic choice to all (100 %) patients enrolled in the study, harboring oncogenic events (mutations/ translocations/ amplifications, etc.) or not. The total number of patients treated in the study will be two hundred across all participating cancer centers (European countries -France; Spain-, Israel, USA and Canada). All centers will realize the same study independently.

Conditions

Metastatic Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  To assess the individual outcome of patients with advanced malignancies, by comparing the progression-free survival (PFS) using a treatment regimen selected by a molecular analysis of a patient's tumor with the PFS for the most recent regimen on which the patient had experienced progression * ARM A : PFS2/PFS1 \>1.5 in 50% of patients * ARM B : PFS2/PFS1 \>1.5 in 40% of patients The primary endpoint of the study is the ratio of the PFS of the current treatment (PFS2) versus the previous treatment (PFS1). Because patients will be enrolled in the study while they are still on treatment (before progression), we expect that PFS for the previous treatment is fully observed. If patients withdrew from the treatment due to treatment related toxicity and lost to follow-up, it is considered that the PFS endpoint is reached. If patients are lost to follow up due to other reasons, PFS is censored at the time of last follow up.

  Up to 6 months

Study Arms (2)

Arm A

EXPERIMENTAL

ARM A patients with an identified oncogenic driver mutations/amplifications/translocations), who will potentially benefit from targeted therapies, either on the market or in clinical trials according to existing knowledge of matching oncogenic events with actionable drugs. This will be detected through Next Generation Sequencing (NGS) performed by Foundation Medicine, CLIA certified.

Procedure: Biopsy

Arm B

EXPERIMENTAL

patients negative for oncogene events (which remains the majority), for whom genome based relevant information will be obtained through functional genomics (micro arrays and gene expression profiling) performed by Institut Gustave Roussy, and innovative computational methods enabling a rational choice of therapies. For such patients we will apply a new prediction model of efficacy of existing and under clinical trial drugs, based on differences in gene expression profiling between tumor and normal biopsies to be matched with relevant genes that are related to drug activities.

Procedure: Biopsy

Interventions

Biopsy PROCEDURE

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent
• Any histologic type of metastatic cancer, (except for lung and brain at US sites), in which histologic normal counterpart can be obtained.
• Progression by RECIST (Response Evaluation Criteria In Solid Tumors) or other criteria on at least one prior regimen for advanced disease.
• Ability to undergo a biopsy or surgical procedure to obtain fresh tumor biopsy paired with its normal counterpart.
• Age from 18 years
• Life expectancy of at least 3 months
• ECOG Performance status of 0 to 1
• Measurable or evaluable disease according to RECIST 1.1 criteria
• For U.S. sites, advanced cancer patients that have exhausted all effective therapy for their disease and have progressed after previous line of therapy (documented disease progression under last treatment received) and conventional methods of assigning new therapy would not be expected to increase survival by more than 3 months.

You may not qualify if:

• Any patient that might require a lung or brain biopsy are excluded (at US sites)
• Alteration of organ function or hematopoietic function as defined by the following criteria:
• Bilirubin \> 2.0 ULN
• Polynuclear neutrophil \< 1.5 x 109/L
• Platelets \< 100 x 10 9/L
• Hemoglobin \< 90 g/L
• Creatinine \> 1.5 ULN
• Calcemia \> 1.5 ULN
• Phosphatemia \> 1.5 ULN
• Coagulation abnormality prohibiting a biopsy
• Symptomatic or progressive brain metastases detected by radio imaging, or meningeal

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (1)

Institut Gustave Roussy

Villejuif, Val De Marne, 94805, France

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Biopsy

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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 Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2013
• First Posted: May 17, 2013
• Study Start: April 23, 2013
• Primary Completion: December 7, 2015
• Study Completion: February 22, 2019
• Last Updated: June 18, 2019

Record last verified: 2019-06

Locations

FR (1)