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Soft Tissue SarcomaRNASARCNCT03375437

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

A study testing Blood and tumor samples in people with Soft Tissue Sarcoma and Advanced Cancer, run by Centre Leon Berard at 10 sites in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Blood and tumor samples
Could I receive a placebo?
No, everyone receives an active treatment
How many people
376 participants
Where
10 sitesFrance
Study dates
15 Feb 2018to 15 Dec 2025
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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).
Show all 12Show fewer
  • 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.

Who cannot join

None listed.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

France10 sites

  • Centre Jean Perrin

    Clermont-Ferrand, 63011

  • Centre Georges-Francois Leclerc

    Dijon, 21079

  • Centre Oscar Lambret

    Lille, 59000

  • CHU de Limoges Hôpital Dupuytren

    Limoges

  • Centre Léon Bérard

    Lyon, 69008

  • Institut de Cancérologie de Lorraine

    Nancy, 54511 cedex

  • Centre Antoine Lacassagne

    Nice

  • Institut Gustave ROUSSY

    Paris

  • Centre Eugène Marquis

    Rennes

  • Institut de Cancérologie de la Loire Lucien Neuwirth

    Saint-Priest-en-Jarez

Other trials in France

About this study

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.

Read the 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).
Being tested
Blood and tumor samples
Keywords
Clinical Trial, Multicenter Trial, NTRK1, NTRK2, NTRK3, ROS1, ALK, RNAseq, entrectinib, STARTRK-2
Medical subject headings
Sarcoma, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Blood and tumor samplesGenetic

    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)

Study groups in NCT03375437
Study groupRoleWhat they receive
NTRK, ROS and ALK molecular screeningExperimentalThe 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.
Receives: Genetic: Blood and tumor samples

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 24 months

Secondary outcomes (4)

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

    the partitioning of STS patients with NTRK1/2/3, ROS1 or ALK gene fusions within the different STS sub-types.

    Measured: 24 months since first inclusion

  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.

    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.

    Measured: 24 months since first inclusion

  3. anti-cancer treatments initiated since inclusion.

    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.

    Measured: 36 months

  4. Overall survival (OS)

    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)

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Dec 2017
  2. Study start15 Feb 2018
  3. Primary completion15 Dec 2024 (estimated)
  4. Study completion15 Dec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Screening
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
376 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03375437
Sponsor's protocol ID
ET17-080 (RNASARC)
Acronym
RNASARC
Status last verified
Aug 2024
First submitted
4 Dec 2017
Last updated
26 Aug 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. doi: 10.1016/S0140-6736(16)30587-6. Epub 2016 Jun 9.

    PubMed 27291997

  • 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.

    PubMed 20490332

  • 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.

    PubMed 27501018

  • 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.

    PubMed 27197880

  • 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.

    PubMed 11431098

  • 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.

    PubMed 7144906

  • 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.

    PubMed 2869410

  • 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.

    PubMed 25264305

  • 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.

    PubMed 24670165

  • 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.

    PubMed 25527197

  • 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.

    PubMed 26216294

  • 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.

    PubMed 24618336

  • 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.

    PubMed 27621408

  • 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.

    PubMed 37054503

Questions about this trial

What is this clinical trial studying?

A study testing Blood and tumor samples in people with Soft Tissue Sarcoma and Advanced Cancer, run by Centre Leon Berard at 10 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 26 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

the proportion of patients with NTRK1/2/3, ROS1 or ALK gene fusions (95% confidence interval) (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03375437, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2024.

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