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

Metastatic Cancer Clinical Trial

— WINTHER  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01856296
• Other study ID #: 2012-A01738-35
• Secondary ID: 2012/1946
• Status: Completed
• Phase: N/A
• Start date: April 23, 2013
• Est. completion date: February 22, 2019

Study information

• Verified date: June 2019
• Source: Gustave Roussy, Cancer Campus, Grand Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 303
• Est. completion date: February 22, 2019
• Est. primary completion date: December 7, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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:

1. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) >2.5 x upper limit of normal (ULN), except for patients with liver metastases, for which AST and ALT > 5.0 ULN is the exclusion criteria.

2. Bilirubin > 2.0 ULN

3. Polynuclear neutrophil < 1.5 x 109/L

4. Platelets < 100 x 10 9/L

5. Hemoglobin < 90 g/L

6. Creatinine > 1.5 ULN

7. Calcemia > 1.5 ULN

8. Phosphatemia > 1.5 ULN

• Coagulation abnormality prohibiting a biopsy

• Symptomatic or progressive brain metastases detected by radio imaging, or meningeal

• Patient who received a personalized therapeutic treatment based on molecular anomaly during the treatment period prior to the WINTHER directed treatment (defining the PFS1). Hormonal therapy may be continued during WINTHER suggested therapy. The exclusion of prior matched targeted therapy includes but is not limited to all targeted therapeutics that are EMA approved and genomically matched to patients. If there are questions about whether or not a prior therapy is matched targeted treatment it will be agreed on by discussion between PIs who are also Clinical Management Committee members; the resolution should take place prior to starting WINTHER directed treatment.

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Procedure:
• Biopsy

Locations

Country	Name	City	State
France	Institut Gustave Roussy	Villejuif	Val De Marne

Sponsors (1)

Lead Sponsor	Collaborator
Gustave Roussy, Cancer Campus, Grand Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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