RNASARC - Molecular Screening Program of Soft Tissue Sarcomas With Complex Genomic Profile to Detect NTRK1/2/3, ROS1 or ALK Gene Fusions. (RNASARC)

April 7, 2023 updated by: Centre Leon Berard
This trial is a multicenter, prospective cohort study aiming to describe molecular profiles of soft tissue sarcoma (STS) with complex genomic profiles in particular to assess the incidence of NTRK1/2/3, ROS1 or ALK gene fusions to direct such patients through an ongoing clinical trial with entrectinib when appropriate. An exploratory translational program is also correlated to this trial in order to analyse immune gene expression.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Following inform consent form (ICF) signature, a formalin-fixed and paraffin-embedded (FFPE) tumor block (archival or a dedicated freshly collected tumor biopsy) will be collected for all enrolled patients and centralized at the biological resources platform of the Centre Léon Bérard.

At reception, a central pathological review will be performed to confirm if quality and quantity of material is acceptable: all tumor sample should present at least 20 % (ideally 30 %) of tumor cells and have a surface area > 5 mm2 (optimal condition is a surface area of 5-25 mm2). If the quality and quantity of tumor sample do not meet the standards, patients will be considered as "screening failure". If standards are met, inclusion will be confirmed and molecular screening will be initiated as well as the translational research program.

The molecular screening to detect NTRK1,2,3, ROS1 or ALK gene rearrangements will be a two-step process, consisting of :

  1. First, immunohistochemistry (IHC) assay to detect protein expression of TRKA/B/C (encoded by NTRK1,2,3), ROS1 or ALK. Only positive IHC samples will continued the 2nd step of molecular screening. Negative IHC patients do not require further NTRK, ROS or ALK gene rearrangement testing; however tumor samples will be further used for additional translational research program presented in Section VII and data about the clinical evolution of these patients will be collected
  2. Second, RNAseq analysis will be performed on positive IHC specimens to detect specific rearrangements in the NTRK1,NTRK2, NTRK3, ROS1 or ALK genes.
  3. Following molecular analyses, screening results will be immediately (within 24 hours) communicated to investigators, GSF-GETO Network and Ignyta representatives in order to recommend patients with NTRK1, NTRK2, NTRK3, ROS1 or ALK rearrangement for formal eligibility determination for potential enrolment in a clinical trial in particular with entrectinib (STARTRK-2; NCT02568267).

Study Type

Interventional

Enrollment (Actual)

376

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Clermont-Ferrand, France, 63011
        • Centre Jean PERRIN
      • Dijon, France, 21079
        • Centre Georges-François Leclerc
      • Lille, France, 59000
        • Centre Oscar LAMBRET
      • Limoges, France
        • CHU de Limoges Hopital Dupuytren
      • Lyon, France, 69008
        • Centre Léon Bérard
      • Nancy, France, 54511 cedex
        • Institut de Cancérologie de Lorraine
      • Nice, France
        • Centre Antoine LACASSAGNE
      • Paris, France
        • Institut Gustave Roussy
      • Rennes, France
        • Centre Eugène Marquis
      • Saint-Priest-en-Jarez, France
        • Institut de cancérologie de la Loire Lucien Neuwirth

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • I1. Male or female patients aged ≥ 12 years at time of informed consent form (ICF) signature.
  • I2. Histologically confirmed diagnosis of advanced /metastatic disease STS with complex genomics (e.g., Leiomyosarcoma [LMS], Undifferentiated Pleomorphic Sarcoma [UPS], pleomorphic liposarcoma/rhabdomyosarcoma [P-LPS/P-RMS], angiosarcoma, malignant peripheral nerve sheath tumor [MPNST], myxofibrosarcoma, fibrosarcoma).
  • I3. Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor sample, with the corresponding hematoxylin and eosin stained slide and a pathological report:

either a tumor archival block (less than 3 years old) or a dedicated freshly collected de novo biopsy performed from one accessible lesion visible by medical imaging and accessible to percutaneous sampling with a diameter of at least 10 mm.

  • I4. Tumor sample meeting following quality/quantity control (QC) criteria confirmed by a central pathological review:

at least 20% (ideally 30%) of tumor cells and a sample size surface area > 5mm2 (ideally 5-25mm2).

  • I5. Patient (and legal guardians if not-emancipated minor) should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study procedures as per protocol.
  • I6. Patient must be covered by a medical insurance.

Non-inclusion criteria:

  • NI1. Patients with non-assessable tumor sample.
  • NI2. Prior treatment with approved or investigational TRK, ROS1, or ALK inhibitors. Any other prior anticancer therapy are allowed with no limit of prior number of treatment lines.
  • NI3. Pregnant or breast-feeding patients.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NTRK, ROS and ALK molecular screening

The molecular screening to detect NTRK1, 2, 3, ROS or ALK gene rearrangements will be a two step process, consisting of:

  1. First, immunohistochemistry (IHC) assay to detect protein expression of TRKA/B/C (encoded by NRTK1,2,3), ROS1 or ALK.
  2. Second, RNAseq analysis will be performed on positive IHC specimens to detect specific rearrangements in the NTRK1, NTRK2, NTRK3, ROS1 or ALK genes.
Genetic: Blood and tumor samples

FFPE tumor block (archival or a dedicated freshly collected tumor biopsy) will be collected for all enrolled patients and centralized.

Blood sampling for Translational Research (optional) (2*10mL EDTA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the proportion of patients with NTRK1/2/3, ROS1 or ALK gene fusions (95% confidence interval)
Time Frame: 24 months
Such molecular pre-screening will allow to direct eligible patients with sarcomas harboring an NTRK1/2/3, ROS1 or ALK fusion to a clinical trial with entrectinib, when judged appropriate by the patient's treating oncologist. Depending of the molecular alterations, other therapeutic options could be envisaged.
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with NTRK1/2/3, ROS1, or ALK gene fusion per histological sub-types of STS with complex genomics
Time Frame: 24 months since first inclusion
the partitioning of STS patients with NTRK1/2/3, ROS1 or ALK gene fusions within the different STS sub-types.
24 months since first inclusion
Clinical characteristics of patients with NTRK1/2/3, ROS1, or ALK gene fusion versus patients with no NTRK1/2/3, ROS1, or ALK gene fusion.
Time Frame: 24 months since first inclusion
Comparisons of quantitative variables will be assessed with Student t-test or Wilcoxon-Mann and Whitney test , as appropriate. Comparisons of qualitative variables will be assessed with the X2 test or the Fisher's exact test, as appropriate.
24 months since first inclusion
anti-cancer treatments initiated since inclusion.
Time Frame: 36 months
anti-cancer treatments initiated since inclusion among patients with NTRK1/2/3, ROS1, or ALK gene fusion and among patients with no NTRK1/2/3, ROS1, or ALK gene fusion.
36 months
Overall survival (OS)
Time Frame: 36 months
Overall survival (OS) among patients with NTRK1/2/3, ROS1, or ALK gene fusion and among patients with no NTRK1/2/3, ROS1, or ALK gene fusion. It will be measured from the date of STS diagnosis to the date of death from any cause. Patients who are alive at the time of analysis will be censored at the date of last contact. OS will be estimated using the Kaplan-Meier method, and will be described in terms of medians along with the associated 2-sided 95% confidence interval (CI)
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Leon Berard

Collaborators

Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2018

Primary Completion (Anticipated)

February 15, 2024

Study Completion (Anticipated)

January 15, 2025

Study Registration Dates

First Submitted

December 4, 2017

First Submitted That Met QC Criteria

December 12, 2017

First Posted (Actual)

December 18, 2017

Study Record Updates

Last Update Posted (Actual)

April 10, 2023

Last Update Submitted That Met QC Criteria

April 7, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ET17-080 (RNASARC)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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