Clinical trial NCT03375437: RNASARC - Molecular Screening Program of Soft Tissue Sarcomas With Complex Genomic Profile to Detect NTRK1/2/3, ROS1 or ALK Gene Fusions.
Official title: RNASARC - Molecular Screening Program of Soft Tissue Sarcomas With Complex Genomic Profile to Detect NTRK1/2/3, ROS1 or ALK Gene Fusions.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Soft Tissue Sarcoma
Advanced Cancer
Metastatic Cancer
Keywords: Clinical Trial
Multicenter Trial
NTRK1
NTRK2
NTRK3
ROS1
ALK
RNAseq
entrectinib
STARTRK-2
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2017-12-18
Enrollment: 376
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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.

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).

Eligibility 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.

Primary outcomes:
measure: the proportion of patients with NTRK1/2/3, ROS1 or ALK gene fusions (95% confidence interval)
timeFrame: 24 months
Secondary outcomes:
measure: Proportion of patients with NTRK1/2/3, ROS1, or ALK gene fusion per histological sub-types of STS with complex genomics
timeFrame: 24 months since first inclusion
measure: 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.
timeFrame: 24 months since first inclusion
measure: anti-cancer treatments initiated since inclusion.
timeFrame: 36 months
measure: Overall survival (OS)
timeFrame: 36 months
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Georges-Francois Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: CHU de Limoges Hôpital Dupuytren
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Gustave ROUSSY
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie de la Loire Lucien Neuwirth
Study officials:
affiliation: Centre Leon Berard
name: Armelle DUFRESNE, MD
role: PRINCIPAL_INVESTIGATOR
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