Exome analysis of tumor DNA and constitutional DNA in patients included in 1st line treatment

Exome analysis

François Ghiringhelli, PU-PH

Emilie Rederstorff, PhD

Bruno CHAUFFERT, MD

Laura MANSI, MD

Antoine ITALIANO, MD

Antoine DROUILLARD, MD

Benoist CHIBAUDEL, MD

Nicolas PENEL, MD

Jaafar BENNOUNA, MD

Nicolas Isanbert, MD

Charles Coutant, PU-PH

The "simple" analysis of the exome can determine somatic and constitutional mutations. The major challenge lies in the translation of sequencing data into clinically relevant information allowing the clinician to guide his decision-making A "complex" analysis of the exome would provide access to structural DNA data, concerning mutational signatures, tumor mutational load, analysis of large deletions, loss of heterozygosity as well as amplification of certain genes which may have an impact on the management of patients.

No data available to date makes it possible to assess the clinical interest of the availability of its additional information resulting from a "complex" analysis compared to a "simple" analysis. The objective of the EXOMA2 study is to assess the proportion of patients for whom the proposed therapy is derived from its additional information (complex analysis) and would not have been possible with a classic exome analysis (simple analysis) .

We hereby formulate the hypothesis that a "complex" analysis on a population presenting a metastatic or locally advanced disease treated early (from the 1st line of treatment) will make it possible to determine therapeutic indications which could not be discovered with a "simple" analysis.

Exome Analysis (Complexe vs Simple) to Help the Therapeutic Decision for the Precision Medicine

A Multicenter, Prospective, Multi-organ Study to Evaluate the Clinical Benefit of an Exome "Complex" Analysis Versus an Exome "Simple" Analysis to Help the Therapeutic Decision for the Precision Medicine

Centre Georges Francois Leclerc

Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Sarcoma

Colorectal Neoplasms

Neoplasms by Histologic Type

Neoplasms, Connective and Soft Tissue

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Soft Tissue Sarcoma

Patients with advanced/metastatic soft-tissue sarcoma

Patients with metastatic colorectal carcinoma

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.

Next Generation Sequencing (NGS): exome, RNA seq

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

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.

For each participant, biological specimens will be collected for molecular analysis :

* Whole blood sample for constitutional characteristics
* Tumor sample (fresh-frozen or formalin-fixed paraffin embedded)

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

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

The time delay between the date of sample receipt by the platform and the date of dispatch of a validated MTB report to physician

Rate of patients for whom a report was transmitted, within the patients for whom the samples were received by the platforms

The time delay between the date of informed consent signature and the date of dispatch of a validated MTB report to physician

Rate of patients for whom a report was transmitted, within the patients for whom signed consent has been signed

The time delay between the date of informed consent signature and the date of sample receipt on platform

Rate of patients for whom samples have been received by platform, within the patients for whom signed consent has been signed

The time delay between the date of sample receipt on platform and the date of nucleic acids receipt on CNRGH

Rate of patients for whom samples have been received by platform, within the patients for whom sending date has been completed on electronic case

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

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

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

The time delay between the date of nucleic acids receipt on CNRGH and the date of receipt of all sequencing files by bioinformatic 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

Rate of patients for whom sequencing have been qualified by CNRGH, within the patients for whom samples have been received by CNRGH

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

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

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

The time delay between the date of bioinformatic analysis availability for interpretation and the date of dispatch of a validated MTB report to physician

Rate of patients for whom bioinformatic analysis has been interpreted by biologist, within the patients for whom bioinformatics analysis have been transmitted

Rate of patients for whom biological report has been discussed by MTB, within the patients for whom bioinformatics analysis have been transmitted

Institut Bergonié

Plateforme labellisée Inca - Institut Bergonié, Bordeaux

Plateforme labellisée Inca - Hôpital Européen Georges Pompidou, Paris

CNRGH, Evry

EUCLID Clinical Trial Platform

Institut National de la Santé Et de la Recherche Médicale, France

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Bronchogenic

cancer patients To explore the phenomena of resistance during the therapeutic response and/or the progression of the pathology, the investigatorswill used a multidisciplinary approach including high-throughput sequencing (Exome-seq and RNAseq) from blood and tumor samples and immunological profil by ELISA

Blood sample RNA_seq at time of diagnostic, best response and relapse ; Biopsy Exom_seq and RNA_seq at time of diagnostic and relapse Immulogical Profiling at time of diagnostic, best response and relapse

cancer patients

PHILIPPE GENNE, PhD

SEBASTIEN VACHENC

CHRISTELLE DE LA FOUCHARDIERE, MD

FERNANDO BAZAN, MD

ISABELLE DESMOULINS, MD

PASCAL FOUCHER, MD

Christelle CLEMENT-DUCHÊNE, MD

CHRISTELLE CLEMENT-DUCHÊNE, MD

AUDE-MARIE SAVOYE, MD

MICHELE BEAU-FALLER, MD

NICOLAS ISAMBERT, MD

DAVID TOUGERON, MD

MARINE GILABERT, MD

PHILIPPE LEVY, MD

NICOLAS GIRARD, MD

FRANCOIS GHIRINGHELLI, MD

Precision medicine is considered to be one of the major issues in patient care. A lot of research has already proven itself with the implementation of targeted therapies including immunotherapies offering patients improved response and survival rates. But despite these major therapeutic advances, resistance to anti-cancer treatment is a major obstacle in the care of patients. Indeed, to date, many patients die of cancer, 9.6 million deaths worldwide in 2018. Nowadays, improving understanding of the mechanisms of resistance of cancer cells to anti-tumor treatments is therefore a major issue. The great diversity of molecular mechanisms involved in the phenomena of resistance to treatment, whether intrinsic (de novo, or primary) or acquired (secondary), constitutes a real therapeutic challenge. Indeed, a better understanding of the mechanisms of resistance would make it possible to explore new therapeutic strategies making it possible to circumvent these phenomena of escape in different types of cancer. It is in this context that the OncoSNIPE project was developed. The objective of this project is to identify early and / or late markers of resistance to treatment in 3 different pathologies concerned with resistance issues: triple negative breast cancer or Lum B or locally advanced or metastatic non -small-cell lung cancer or pancreatic cancer. In this project, in order to best cover the diversity of mechanisms involved in these resistances, the investigators propose a multidisciplinary approach with clinical, genomic, transcriptomic and immunological dimensions of the pathology through the data collected from 600 patients (200 for each pathology) for 4 years

Precision medicine is considered to be one of the major issues in patient care. A lot of research has already proven itself with the implementation of targeted therapies including immunotherapies offering patients improved response and survival rates. But despite these major therapeutic advances, resistance to anti-cancer treatment is a major obstacle in the care of patients. Indeed, to date, many patients die of cancer, 9.6 million deaths worldwide in 2018. Nowadays, improving understanding of the mechanisms of resistance of cancer cells to anti-tumor treatments is therefore a major issue. The great diversity of molecular mechanisms involved in the phenomena of resistance to treatment, whether intrinsic (de novo, or primary) or acquired (secondary), constitutes a real therapeutic challenge. Indeed, a better understanding of the mechanisms of resistance would make it possible to explore new therapeutic strategies making it possible to circumvent these phenomena of escape in different types of cancer. It is in this context that the OncoSNIPE project was developed. The objective of this project is to identify early and / or late markers of resistance to treatment in 3 different pathologies concerned with resistance issues : triple negative breast cancer or lum B or locally advanced or metastatic non- small-cell lung cancer or pancreatic cancer. In this project, in order to best cover the diversity of mechanisms involved in these resistances, the investigators propose a multidisciplinary approach with clinical, genomic, transcriptomic and immunological dimensions of the pathology through the data collected from 600 patients (200 for each pathology) for 4 years.

The patient populations targeted in this study have one common thing: rapid progression of their pathology, making it possible to obtain models for evaluating markers of early and / or late responses over the period of follow-up of 2-year post-inclusion patients, and thus provide the information necessary to understand the resistance mechanisms.

To explore the phenomena of resistance, during the therapeutic response and / or the progression of the pathology, the investigators will used a multidisciplinary approach including high-throughput sequencing (Exome-seq and RNAseq) and immunological profil by ELISA . Patients will have long-term follow-up with different biological samples, at baseline (blood and biopsy) and at each tumoral evaluation or tumoral progression evaluated by medical imaging.

In this study a part of samples (blood and biopsies) will be collected specifically for this study. This is why the study is therefore interventional

OncoSNIPE - Study of Molecular Profiles Associated With the Development of Resistance in Solid Cancer Patients

Molecular Profiles Associated With Resistance Development in Cancer Patients. Prospective Exploratory Study From 3 Cancer Locations: TNBC or Locally Advanced or Metastatic, Non-small Cell or Pancreatic or Bronchial Cancers

1. Genomic changes associated with early and/or late resistance to treatment given alone or in combination in patients \[ Time Frame: Through study completion, up to 2 years \]
2. Transcriptomic changes associated with early and/or late resistance to treatment given alone or in combination in patients \[ Time Frame: Through study completion, up to 2 years \]
3. Immunophenotypic changes associated with early and/or late resistance to treatment given alone or in combination in patients \[ Time Frame: Through study completion, up to 2 years \]

Clinical data from Baseline until 24 months

Oncodesign SA

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Breast Neoplasms

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

745 patients with HER2-positive and triple-negative breast cancer who underwent neoadjuvant therapy followed by breast surgery.

137 patients with metastatic prostate cancer

Somatic and germline whole exome sequencing will be analyzed for prostate and HER2-positive breast cancer

Somatic whole exome and germline whole genome sequencing will be analyzed for triple-negative breast cancer

whole exome and whole genome sequencing analysis

Marina Bessel

André Mancini

Eduardo K Neto

Gláucio A Bertollo

Daniela L Louzeiro

Flávio Brandão

Angélica N Rodrigues

Aline BL Gongora

Williams F Barra

Edilmar M Santos

Alessandra Notari

Cristiano P Souza

Henrique G Ascenço

Ruffo Freitas Jr.

Pedro ER Liedke

Gustavo Werutsky

Juliana J Menezes

Christina PO Kussler

Lilian AR Barros

Vitor F Vasconcellos

Daniela D Rosa, PhD

This project aims to perform complete sequencing of the somatic (tumor) and germline exomes during clinical investigation of cancer patients treated through the Brazilian Unified Health System to generate genomic and phenotypic data for the Brazilian Ministry of Health's National Precision Genomics and Health Program, called Genomas Brasil, as well as to collect data on the population's ancestry.

In Brazil, the most frequent types of neoplasm are prostate cancer in men and breast cancer in women. Understanding the molecular variants in tumors, which result from mutations and variants that occur during carcinogenesis, can affect treatment response and disease prognosis and is an important target of oncology research. Detecting hereditary genetic syndromes also helps in oncological follow-up, allowing prediction of the risk of new neoplasms. This project aims to perform complete sequencing of the somatic (tumor) and germline exomes during clinical investigation of cancer patients treated through the Brazilian Unified Health System to generate genomic and phenotypic data for the Brazilian Ministry of Health's National Precision Genomics and Health Program, called Genomas Brasil, as well as to collect data on the population's ancestry.

Whole blood and formalin-fixed paraffin-embedded (FFPE) tissue

Onco-Genomas Brasil: Mapping Breast and Prostate Cancer in the Brazilian Public Health System

Characterize the genomic ancestry of Brazilian patients with breast and prostate cancer

Mutations in the somatic and germline exomes/genomes of women with HER2-positive and triple-negative breast cancer and of men with metastatic prostate cancer will be described

Mutations in the somatic and germline exomes/genomes will be correlated to clinical outcomes

Mutations in the somatic and germline exomes/genomes will be correlated to response to treatments

Identify mutations in germline exomes/genomes related to hereditary cancer syndromes

Ministry of Health, Brazil

Hospital Moinhos de Vento

Symptoms and General Pathology

Neoplasm Metastasis

Blood samples and, for some patients, buccal (mouth cell) samples will be collected at diagnosis and/or relapse. Solid tumor samples will be collected in the normal course of treatment, from biopsy, blood or other specimens. For blood-based cancers such as leukemia, blood and bone marrow specimens will be collected before treatment begins, on day 29 and possibly at a later time point if relapse occurs.

Patients may meet, depending on test results, with their physician and a genetic counselor to discuss possible changes in their treatment options and/or lifestyle changes.

Cancer Treatment Options

Stuart S Winter, MD

The goal of this study is to develop a new, local system that will use special tests based on patients' genetic makeup to better tailor cancer care at the University of New Mexico Cancer Center.

The Food and Drug Administration has already approved over forty (40) drugs to treat cancer patients based on specific genetic makeup, and more agents are in development that will support this new approach to treatment, often referred to as "personalized medicine."

The goal of performing specific tests on patients' genetic material is to discover tumor-specific, single nucleotide variations (SNVs) and other forms of genetic changes (called epigenetic changes) that can be detected when comparing normal tissue and tumor tissue. This can help guide cancer care decisions that may be more effective for patients. These will be called clinically actionable findings, or CAF.

Additional health related findings may be made, not related to cancer but to other conditions, diseases or syndromes. These are called secondary findings (SF). In this study the investigators will also measure how often they find SF and will discuss their possible impact on other aspects of patients' health. If patients want to know about these findings, they will be discussed with a panel of experts including genetic counselors.

Finally, the investigators will compare how often CAF and SF differ from those identified in nationwide samples.

For brevity, the investigators include the approaches of whole genome sequencing, whole exome sequencing of just the protein-coding exons, enrichment and sequencing of methylated DNA and RNA or transcriptome-sequencing under the broad category term, Whole Genome Sequencing (WGS).

The development of rapid and low cost next-generation genome sequencing technologies brings the promise of a new era of precision therapeutics to clinical practice, but it is associated with significant challenges, including reproducible generation of high-quality sequence data and the need for comprehensive data analysis and interpretation that is translatable to clinical action. Equally critical are the ethical, legal, and social issues surrounding the introduction of WGS testing and its clinical application in multiethnic, multicultural populations, particularly those who have historically experienced discrimination or even unethical research practices. Of particular concern are issues surrounding the privacy, ownership, storage, and use of WGS data.

Genome Sequencing of Human Cancer Tissues

The investigators will utilize new genomics technologies in to identify potentially Clinically Actionable Findings (CAF) in patient tumor and other samples. Based on individual patient data, alternative treatment options will be offered to patients.

The investigators will measure the frequency with which clinically actionable findings (CAF) that could impact current patient care decisions occur in tumor and other samples.

Determine whether CAF identified in the unique patient populations treated at the University of New Mexico Cancer Center differ from those identified in nationwide data sets such as The 1000 Genomes Project or The Cancer Genome Atlas (TCGA) data collections.

Identify the numbers and types technological, social, ethical and/or legal barriers that might limit the use of genomics information in patient care at the University of New Mexico Cancer Center and the University of New Mexico Health Sciences Center. The investigators will assess the frequency of use of CAF by local treating physicians. They will assess how often cancer treatment choice is altered as a result of providing CAF to physicians and patients. The investigators will assess how often identified CAF are entered into patient medical records. They will assess the frequency with which patients choose to receive information about potentially detrimental SF unrelated to their cancer care.

Identify other genomics-based findings in patient samples unrelated to cancer care, but which might impact other aspects of patients' health. These will be referred to as Secondary Findings, or SF. For example, if a SF is identified that suggests an increased risk of diabetes, this would be considered a secondary finding. This will be discussed by a panel of medical experts, and if patients wish to have this information returned to them, their doctor and genetic counselor will discuss the SF. Patients can choose not to have SF returned to them.

Determine whether SF identified in the unique patient populations treated at the University of New Mexico Cancer Center differ from those identified in nationwide samples such as The 1000 Genomes Project or The Cancer Genome Atlas (TCGA).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Exome Analysis (Complexe vs Simple) to Help the Therapeutic Decision for the Precision Medicine	NCT04614480	Cancer	Exome analysis	18 Years -	Centre Georges Francois Leclerc
Molecular Profiling to Improve Outcome of Patients in Cancer. A Pilot Study	NCT03546127	Colorectal Carc... Soft Tissue Sar...	Next Generation...	18 Years -	Institut National de la Santé Et de la Recherche Médicale, France
Exome Analysis (Complexe vs Simple) to Help the Therapeutic Decision for the Precision Medicine	NCT04614480	Cancer	Exome analysis	18 Years -	Centre Georges Francois Leclerc
Molecular Profiling to Improve Outcome of Patients in Cancer. A Pilot Study	NCT03546127	Colorectal Carc... Soft Tissue Sar...	Next Generation...	18 Years -	Institut National de la Santé Et de la Recherche Médicale, France
OncoSNIPE - Study of Molecular Profiles Associated With the Development of Resistance in Solid Cancer Patients	NCT04548960	CANCER	cancer patients	18 Years -	Oncodesign SA
Exome Analysis (Complexe vs Simple) to Help the Therapeutic Decision for the Precision Medicine	NCT04614480	Cancer	Exome analysis	18 Years -	Centre Georges Francois Leclerc
Onco-Genomas Brasil: Mapping Breast and Prostate Cancer in the Brazilian Public Health System	NCT05306600	Breast Cancer Prostate Cancer	whole exome and...	18 Years -	Hospital Moinhos de Vento
Genome Sequencing of Human Cancer Tissues	NCT02105545	Cancer	Cancer Treatmen...	-	New Mexico Cancer Care Alliance

Spots Global Cancer Trial Database for exome

Every month we try and update this database with for exome cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for exome

Every month we try and update this database with for exome cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for exome cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.