Molecular Profiling to Improve Outcome of Patients in Cancer. A Pilot Study

Study Overview
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Brief Summary
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Next Generation Sequencing in cancer: a feasibility study in France to assess sample circuit and to perform analyzes within a limited time.

Detailed Description
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The first France disease genomic medicine program in the field of cancer has been retained by the 2025 Genomic Medicine France Plan. This program, called MULTIPLI encompasses two innovative personalized medicine clinical trials in soft-tissue sarcoma and colorectal carcinoma involving targeted molecules according to the tumor profile of each patient. This 1st clinical research program aims implementing exome sequencing and RNA sequencing to determine the genomic profile and to provide a therapeutic decision for each patient. Genomic analyzes will be performed on different technical platforms: samples will be collected in each investigating center, nucleic acids extraction will be performed on two genetic platforms, Inca labeled and identified for the purpose of this study: Institut Bergonié and Hôpital Européen Georges Pompidou. CNRGH (Centre National de Recherche en Génomique Humaine) was retained for operational platform genomics and Institut Bergonie for bioinformatics data processing. Each genomic profile will be discussed within a multidisciplinary tumor board which aims at providing a therapeutic decision for each patient and to propose a targeted treatment in case of actionable molecular alteration. The purpose of this program is to perform analysis on a set of gene, in order to provide results no more than after 6 weeks after the sample arrival on the biopathological platform. This gene panel analysis is based on the predefined list of genes that are direct targets of the drugs available in the MULTIPLI program. Before implanting this program in a large-scale launch, it was essential to set up a pilot study in order to evaluate both sample's management between several platforms, and the time to report the results, and to verify that it was in line with the objectives set.

Official Title
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Molecular Profiling to Improve Outcome of Patients in Cancer. A Pilot Study (MULTIPLI-0)

Conditions
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Colorectal Carcinoma, Soft Tissue Sarcoma

Intervention / Treatment
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* Genetic: Next Generation Sequencing (NGS): exome, RNA seq


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients Disease: Advanced and/or metastatic soft-tissue sarcoma OR metastatic carcinoma Patient consenting to tumor sequencing, secondary reuse of their data Patient informed about this study Exclusion Criteria: N/A

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| STS<br>Patients with advanced/metastatic soft-tissue sarcoma | Genetic: Next Generation Sequencing (NGS): exome, RNA seq<br>* Tumor and blood samples will be sequenced at medium-high coverage at the whole genome (exome) and transcriptome levels (RNA Seq). This will allow detecting variants in a larger set of samples even though only from the main clone will be precisely measured. The whole exome will be performed at a mean coverage of at least 60x for the normal DNA samples and 120x for the tumor DNA samples. The transcriptome of the tumor will be performed at enough depth of coverage to detect gene fusions, transcriptome variants and measure the digital expression of already annotated isoforms. For both sequencing configurations: Data from each cancer and normal genome will be analysed for the presence of somatic variants. DNA and RNA sequencing results will be integrated. Technical replication for the mutations / chromosome alterations / transcript fusions that most likely drive the tumour process will be performed via Target Resequencing of the genomic / coding regions of interest.<br>|
| CCR<br>Patients with metastatic colorectal carcinoma | Genetic: Next Generation Sequencing (NGS): exome, RNA seq<br>* Tumor and blood samples will be sequenced at medium-high coverage at the whole genome (exome) and transcriptome levels (RNA Seq). This will allow detecting variants in a larger set of samples even though only from the main clone will be precisely measured. The whole exome will be performed at a mean coverage of at least 60x for the normal DNA samples and 120x for the tumor DNA samples. The transcriptome of the tumor will be performed at enough depth of coverage to detect gene fusions, transcriptome variants and measure the digital expression of already annotated isoforms. For both sequencing configurations: Data from each cancer and normal genome will be analysed for the presence of somatic variants. DNA and RNA sequencing results will be integrated. Technical replication for the mutations / chromosome alterations / transcript fusions that most likely drive the tumour process will be performed via Target Resequencing of the genomic / coding regions of interest.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delay time to send a validated exome sequencing report from sample receipt | The time delay between the date of sample receipt by the platform and the date of dispatch of a validated MTB report to physician | an average of 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of patients with samples received by Platform for whom a validated exome sequencing report is available | Rate of patients for whom a report was transmitted, within the patients for whom the samples were received by the platforms | Throughout the study period, on average of 3 months | 
| Delay time to send a validated exome sequencing report from signature to informed consent by the patient | The time delay between the date of informed consent signature and the date of dispatch of a validated MTB report to physician | an average of 8 weeks | 
| The rate of patients with signed informed consent for whom a validated exome sequencing report is available | Rate of patients for whom a report was transmitted, within the patients for whom signed consent has been signed | Throughout the study period, on average of 3 months | 
| Delay time to receive sample on Platform from signature of informed consent | The time delay between the date of informed consent signature and the date of sample receipt on platform | on average of 2 weeks | 
| The rate of patients with signed informed consent for whom samples have been received by platform | Rate of patients for whom samples have been received by platform, within the patients for whom signed consent has been signed | Throughout the study period, on average of 3 months | 
| Delay time to receipt nucleic acids on CNRGH from samples receipt on platform | The time delay between the date of sample receipt on platform and the date of nucleic acids receipt on CNRGH | on average of 1 week | 
| The rate of patients with samples sending date completed on electronic case for whom samples have been received by platform | Rate of patients for whom samples have been received by platform, within the patients for whom sending date has been completed on electronic case | Throughout the study period, on average of 3 months | 
| The rate of patients with samples received on platform for whom these samples have been qualified in first step by platform and nucleic acids have been received by CNRGH | Rate of patients for whom samples have been qualified in first step by platform and nucleic acids received by CNRGH, within the patients for whom samples have been received by platform | Throughout the study period, on average of 3 months | 
| The rate of patients with samples received on Platform for whom these samples have been qualified in second step by platform and nucleic acids have been received by CNRGH | Rate of patients for whom samples have been qualified in second step by platform and nucleic acids received by CNRGH, within the patients for whom samples have been received by platform | Throughout the study period, on average of 3 months | 
| The rate of patients with samples received on platform for whom these samples have been qualified in first and second step by Platform and nucleic acids have been received by CNRGH | Rate of patients for whom samples have been qualified in first and second step by platform and nucleic acids received by CNRGH, within the patients for whom samples have been received by platform | Throughout the study period, on average of 3 months | 
| Delay time to receive all sequencing files from nucleic acids receipt on CNRGH | The time delay between the date of nucleic acids receipt on CNRGH and the date of receipt of all sequencing files by bioinformatic platform | on average of 3 weeks | 
| The rate of patients with nucleic acids received on CNRGH for whom all sequencing files have been qualified by bioinformatics platform | Rate of patients for whom all sequencing files have been qualified by bioinformatics platform, within the patients for whom samples have been received by CNRGH | Throughout the study period, on average of 3 months | 
| The rate of patients with nucleic acids received on CNRGH for whom sequencing have been qualified by CNRGH | Rate of patients for whom sequencing have been qualified by CNRGH, within the patients for whom samples have been received by CNRGH | Throughout the study period, on average of 3 months | 
| Delay time to receive bioinformatics analysis for interpretation from availability of all sequencing files | The time delay between the date of receipt of all sequencing files by bioinformatics platform and the date of receipt of bioinformatics analysis by biologist for interpretation | on average of 1 week | 
| The rate of patients with sequencing files received by bioinformatic Platform for whom these files have been qualified for analysis | Rate of patients for whom all sequencing file have been qualified by bioinformatic platform, within the patients for whom all sequencing file have been received by bioinformatic platform | Throughout the study period, on average of 3 months | 
| The rate of patients with sequencing files received by bioinformatic Platform for whom analysis have been transmitted for interpretation | Rate of patients for whom bioinformatic analysis have been transmitted for interpretation, within the patients for whom all sequencing file have been received by bioinformatic platform | Throughout the study period, on average of 3 months | 
| Delay time to send a validated exome sequencing report from availability of bioinformatic analysis | The time delay between the date of bioinformatic analysis availability for interpretation and the date of dispatch of a validated MTB report to physician | on average of 1 week | 
| The rate of patients with bioinformatic analysis available for interpretation for whom biological interpretation has been performed | Rate of patients for whom bioinformatic analysis has been interpreted by biologist, within the patients for whom bioinformatics analysis have been transmitted | Throughout the study period, on average of 3 months | 
| The rate of patients with bioinformatic analysis available for interpretation for whom results has been discussed by MTB | Rate of patients for whom biological report has been discussed by MTB, within the patients for whom bioinformatics analysis have been transmitted | Throughout the study period, on average of 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exome, Next Generation Sequencing, Colorectal carcinoma, RNA sequencing, Soft-tissue sarcoma