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

NCT03375437 | Active Not Recruiting

• 1 other identifier: ET17-080 (RNASARC)
• Study Type: interventional
• Target: 376
• Locations: 1 country
• Sites: 10

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.

Conditions

Soft Tissue Sarcoma; Advanced Cancer; Metastatic Cancer

Keywords

Clinical Trial; Multicenter Trial; NTRK1; NTRK2; NTRK3; ROS1; ALK; RNAseq; entrectinib; STARTRK-2

Outcome Measures

Primary Outcomes (1)

• the proportion of patients with NTRK1/2/3, ROS1 or ALK gene fusions (95% confidence interval)

  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 Outcomes (4)

• Proportion of patients with NTRK1/2/3, ROS1, or ALK gene fusion per histological sub-types of STS with complex genomics

  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.

  24 months since first inclusion

• anti-cancer treatments initiated since inclusion.

  36 months

• Overall survival (OS)

  36 months

Study Arms (1)

NTRK, ROS and ALK molecular screening

EXPERIMENTAL

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

Interventions

Blood and tumor samples GENETIC

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)

NTRK, ROS and ALK molecular screening

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Centre Leon Berard: lead
• Hoffmann-La Roche: collaborator

Study Sites (10)

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Georges-Francois Leclerc

Dijon, 21079, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

CHU de Limoges Hôpital Dupuytren

Limoges, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Institut de Cancérologie de Lorraine

Nancy, 54511 cedex, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Institut Gustave ROUSSY

Paris, France

Location

Centre Eugène Marquis

Rennes, France

Location

Institut de Cancérologie de la Loire Lucien Neuwirth

Saint-Priest-en-Jarez, France

Location

Related Publications (14)

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  PMID: 27291997 BACKGROUND

• Jain S, Xu R, Prieto VG, Lee P. Molecular classification of soft tissue sarcomas and its clinical applications. Int J Clin Exp Pathol. 2010 Apr 23;3(4):416-28.

  PMID: 20490332 BACKGROUND

• Fleitas T, Ibarrola-Villava M, Ribas G, Cervantes A. MassARRAY determination of somatic oncogenic mutations in solid tumors: Moving forward to personalized medicine. Cancer Treat Rev. 2016 Sep;49:57-64. doi: 10.1016/j.ctrv.2016.07.007. Epub 2016 Jul 29.

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• Schmidt KT, Chau CH, Price DK, Figg WD. Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment. J Clin Pharmacol. 2016 Dec;56(12):1484-1499. doi: 10.1002/jcph.765. Epub 2016 Jun 17.

  PMID: 27197880 BACKGROUND

• Nakagawara A. Trk receptor tyrosine kinases: a bridge between cancer and neural development. Cancer Lett. 2001 Aug 28;169(2):107-14. doi: 10.1016/s0304-3835(01)00530-4.

  PMID: 11431098 BACKGROUND

• Pulciani S, Santos E, Lauver AV, Long LK, Aaronson SA, Barbacid M. Oncogenes in solid human tumours. Nature. 1982 Dec 9;300(5892):539-42. doi: 10.1038/300539a0. No abstract available.

  PMID: 7144906 BACKGROUND

• Martin-Zanca D, Hughes SH, Barbacid M. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature. 1986 Feb 27-Mar 5;319(6056):743-8. doi: 10.1038/319743a0.

  PMID: 2869410 BACKGROUND

• Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC, Le LP, Zheng Z, Tan W, Stephenson P, Shreeve SM, Tye LM, Christensen JG, Wilner KD, Clark JW, Iafrate AJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20;371(21):1963-71. doi: 10.1056/NEJMoa1406766. Epub 2014 Sep 27.

  PMID: 25264305 BACKGROUND

• Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. doi: 10.1056/NEJMoa1311107.

  PMID: 24670165 BACKGROUND

• Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov. 2015 Jan;5(1):25-34. doi: 10.1158/2159-8290.CD-14-0765. Epub 2014 Dec 19.

  PMID: 25527197 BACKGROUND

• Doebele RC, Davis LE, Vaishnavi A, Le AT, Estrada-Bernal A, Keysar S, Jimeno A, Varella-Garcia M, Aisner DL, Li Y, Stephens PJ, Morosini D, Tuch BB, Fernandes M, Nanda N, Low JA. An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. Cancer Discov. 2015 Oct;5(10):1049-57. doi: 10.1158/2159-8290.CD-15-0443. Epub 2015 Jul 27.

  PMID: 26216294 BACKGROUND

• Judson I, Verweij J, Gelderblom H, Hartmann JT, Schoffski P, Blay JY, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, Krarup-Hansen A, Alcindor T, Marreaud S, Litiere S, Hermans C, Fisher C, Hogendoorn PC, dei Tos AP, van der Graaf WT; European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014 Apr;15(4):415-23. doi: 10.1016/S1470-2045(14)70063-4. Epub 2014 Mar 5.

  PMID: 24618336 RESULT

• Ryan CW, Merimsky O, Agulnik M, Blay JY, Schuetze SM, Van Tine BA, Jones RL, Elias AD, Choy E, Alcindor T, Keedy VL, Reed DR, Taub RN, Italiano A, Garcia Del Muro X, Judson IR, Buck JY, Lebel F, Lewis JJ, Maki RG, Schoffski P. PICASSO III: A Phase III, Placebo-Controlled Study of Doxorubicin With or Without Palifosfamide in Patients With Metastatic Soft Tissue Sarcoma. J Clin Oncol. 2016 Nov 10;34(32):3898-3905. doi: 10.1200/JCO.2016.67.6684. Epub 2016 Sep 30.

  PMID: 27621408 RESULT

• Dufresne A, Pissaloux D, Ngo C, Penel N, Le Cesne A, Macagno N, Vanacker H, Henon C, Jean-Denis M, Rughoo K, Tirode F, Blay JY, Brahmi M. Natural history and treatment efficacy in an ambispective case series of NTRK-rearranged mesenchymal tumors. ESMO Open. 2023 Apr;8(2):101202. doi: 10.1016/j.esmoop.2023.101202. Epub 2023 Apr 11.

  PMID: 37054503 DERIVED

MeSH Terms

Conditions

Sarcoma; Neoplasm Metastasis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Armelle DUFRESNE, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2017
• First Posted: December 18, 2017
• Study Start: February 15, 2018
• Primary Completion: December 15, 2024
• Study Completion: December 15, 2025
• Last Updated: August 26, 2024

Record last verified: 2024-08

Locations

FR (10)