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

N/AActive Not RecruitingNCT03375437

Centre Leon Berard376 enrolled

Overview

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.

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

Allocation

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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.

Locations (10)

Centre Jean Perrin

Clermont-Ferrand, France

Centre Georges-Francois Leclerc

Dijon, France

Centre Oscar Lambret

Lille, France

CHU de Limoges Hôpital Dupuytren

Limoges, France

Centre Léon Bérard

Lyon, France

Institut de Cancérologie de Lorraine

Nancy, France

Centre Antoine Lacassagne

Nice, France

Institut Gustave ROUSSY

Paris, France

Centre Eugène Marquis

Rennes, France

Institut de Cancérologie de la Loire Lucien Neuwirth

Saint-Priest-en-Jarez, France

Outcomes

Primary Outcomes

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.

Time frame: 24 months

Secondary Outcomes

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.

Time frame: 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.

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.

Time frame: 24 months since first inclusion

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.

Time frame: 36 months

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)