ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03375437
Recruitment Status : Recruiting
First Posted : December 18, 2017
Last Update Posted : June 13, 2018
Sponsor:
Collaborator:
Ignyta, Inc.
Information provided by (Responsible Party):
Centre Leon Berard

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Soft Tissue Sarcoma Advanced Cancer Metastatic Cancer Genetic: Blood and tumor samples Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 750 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: RNASARC - Molecular Screening Program of Soft Tissue Sarcomas With Complex Genomic Profile to Detect NTRK1/2/3, ROS1 or ALK Gene Fusions.
Actual Study Start Date : February 15, 2018
Estimated Primary Completion Date : February 15, 2020
Estimated Study Completion Date : January 15, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: NTRK, ROS and ALK molecular screening 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)





Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03375437


Contacts
Contact: Armelle DUFRESNE, MD (0)4 69 85 61 47 ext +33 armelle.dufresne@lyon.unicancer.fr

Locations
France
Centre Georges-Francois Leclerc Recruiting
Dijon, France, 21079
Contact: Nicolas ISAMBERT, MD       nisambert@cgfl.fr   
Sub-Investigator: Céline CHARON BARRA, MD         
Sub-Investigator: Audrey HENNEQUIN, MD         
Sub-Investigator: Alice HERVIEU, MD         
Sub-Investigator: Sylvie ZANETTA, MD         
Centre Oscar Lambret Recruiting
Lille, France, 59000
Contact: Nicolas PENEL, MD         
Principal Investigator: Nicolas PENEL, MD         
Sub-Investigator: Fredrik LAESTADIUS, MD         
Sub-Investigator: Diane PANNIER, MD         
Sub-Investigator: Yves-Marie ROBIN, MD         
Sub-Investigator: Thomas RYCKEWAERT, MD         
CHU de Limoges Hôpital Dupuytren Recruiting
Limoges, France
Contact: Valérie LEBRUN-LY, MD         
Principal Investigator: Valérie LEBRUN-LY, MD         
Sub-Investigator: Sandrine LAVAU-DENES, MD         
Sub-Investigator: Isabelle POMMEPUY, MD         
Centre Léon Bérard Recruiting
Lyon, France, 69008
Contact: Armelle DUFRESNE, MD         
Sub-Investigator: Jean-Yves BLAY, MD         
Sub-Investigator: Mehdi BRAHMI, MD         
Sub-Investigator: Philippe CASSIER, MD         
Sub-Investigator: Nadège CORRADINI, MD         
Sub-Investigator: Isabelle RAY-COQUARD, MD         
Institut de Cancérologie de la Loire Lucien Neuwirth Recruiting
Saint-Priest-en-Jarez, France
Contact: Olivier COLLARD, MD       olivier.collard@icloire.fr   
Principal Investigator: Olivier COLLARD, MD         
Sponsors and Collaborators
Centre Leon Berard
Ignyta, Inc.
Investigators
Principal Investigator: Armelle DUFRESNE, MD Centre Leon Berard

Publications of Results:
Other Publications:

Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT03375437     History of Changes
Other Study ID Numbers: ET17-080 (RNASARC)
First Posted: December 18, 2017    Key Record Dates
Last Update Posted: June 13, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centre Leon Berard:
Clinical Trial
Multicenter Trial
NTRK1
NTRK2
NTRK3
ROS1
ALK
RNAseq
entrectinib
STARTRK-2

Additional relevant MeSH terms:
Sarcoma
Neoplasm Metastasis
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplastic Processes
Pathologic Processes