Program to Establish the Genetic and Immunologic Profile of Patient's Tumor for All Types of Advanced Cancer

Study Overview
=================
Brief Summary
-----------------
It is a non-randomized, multicentric, cohort study, combined with a biological sample collection, a clinical data collection and with a genetic and immunologic biomarkers study. The ProfiLER program aims to implement a personalized cancer medicine approach by proposing to establish the genetic and immunologic profile of the tumor for patients with an advanced malignant tumor, in order to define a map of genetic (for the pre-identified target genes) and immunologic profiles for all the studied types of cancer. This study will also allow adapting the therapeutic management of these patients, if needed, by giving them targeted therapies or immunotherapies (commercialized on in ongoing clinical trials), based on the recommendations of the multidisciplinary molecular board. The genetic and immunologic profile of the tumor will be determined from archival or fresh collected (biopsy of a reachable lesion) tumor sample and from a blood sample. The correlation between genetic profiles of the tumor, patients immunity status and clinical data (progression, tumor response, etc.) collected from the patient medical records will probably allow us to identify biomarkers with a potential predictive value and to determine if some genetic disorders are linked to immunity status alterations.

Detailed Description
-----------------
Determination of the tumor profile and review in multidisciplinary molecular board: The genetic and immunologic profile will be performed from the available tumor sample and from a blood sample. Genetic profile: Research of mutations/insertions/deletions for an array of predefined genes in tumor deoxyribonucleic acid by high-throughput sequencing Analysis of copy number variations of genes on tumor deoxyribonucleic acid by microarray-based comparative genomic hybridization Analysis of rearrangements involving the gene Anaplastic Lymphoma Kinase that can't be detected by Next Generation Sequencing or array Comparative Genomic Hybridization (balanced translocations) by means of fluorescent hybridization probes on tumor samples Immunologic profile: analysis of the expression of relevant immunologic markers Clinical data collection: Patients' clinical data will be collected from the patient medical record. This study is not a treatment evaluation. Patients' follow-up and treatment will be performed according to the center local practices or to the specificities of a clinical trial in which the patient would have been enrolled, depending on the recommendations given by the multidisciplinary molecular board, with the review of the tumor genetic profile.

Official Title
-----------------
Program to Establish the Genetic and Immunologic Profile of Patient's Tumor for All Types of Advanced Cancer

Conditions
-----------------
Neoplasms

Intervention / Treatment
-----------------
* Genetic: Blood and tumor samples


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed diagnosis of advanced (locally-advanced or metastatic) malignant tumor of any histological type Tumor sample available to determine the genetic profile: either archival tumor sample [FFPE (formalin fixed and paraffin embedded)] or perform a new biopsy on an accessible lesion (left at the investigator's appreciation). For biopsies, presence of at least one tumor lesion with a diameter ≥ 20 mm, visible by medical imaging and accessible to repeatable percutaneous (needle biopsies 18 gauge or larger) sampling that permit core needle biopsy (ideally 4 cores) without unacceptable risk of a major procedural complication. Please note that brain and bone lesions are not considered as accessible lesions. Patient with 1st, 2nd or 3rd line therapy (NB: endocrine therapy (monotherapy) are not considered as line therapy) for advanced / metastatic cancer. For patients over 70 years of age, a Performance Status (PS) of 0 on the ECOG scale. Patient must be covered by a medical insurance. Informed consent signed by the patient and/or by parents (or legal representative) for patients below 18. Exclusion Criteria: No tumor sample available.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blood and tumor samples<br> | Genetic: Blood and tumor samples<br>* Genetic: Establishment of the genetic and immunologic profile Whole blood sampling : 1 tube for the constitutional DNA extraction; 3 tubes for ancillary studies and research. Collection of the available archival tumor sample (frozen or FFPE). If there's no available sample, the investigator will prescribe a biopsy of a reachable lesion. With the established profile, recommendations will be given by a multidisciplinary molecular board.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish a map of genetic profiles (for the pre-identified target genes) for all types of advanced malignant tumors. | Description of the incidence rates of each detected genetic disorder among the pre-identified target genes in the global cohort and for each histological type. | at least 3 years after patient enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish a map of immunologic profiles for all types of advanced malignant tumors. | Description of the incidence rates of each detected immunologic disorder in the global cohort and for each histological type. | at least 3 years after patient enrollment | 
| Determine for each histological type of tumor, characteristic profiles of genetic and/or immunologic disorders and disorders that might be common to several histological types. | Comparison of the genetic and immunologic profiles between patients with the same tumor type or between tumors of different types. | at least 3 years after patient enrollment | 
| Identify genetic and/or immunologic biomarkers (or molecular profiles) with a potential predictive value on response to treatments. | Tumor response (determined by the investigator and/or the radiologist) assessed after each treatment received by the patient during his/her whole participation to the study (if data are available in the medical record). | at least 3 years after patient enrollment | 
| Identify biomarkers (constitutional or somatic alterations in tumor cells) that might be correlated with systemic or local alterations of the immunity status observed in some patients with advanced cancers | lymphopenia, over-representation of Treg, dendritic cells alterations, | at least 3 years after patient enrollment | 
| Assess the changes of genetic and/or immunologic profiles in case of progressive disease |  | at least 3 years after patient enrollment | 
| Number of patients with a recommanded therapy based on their molecular profil and/or for whom the therapy hs been administrated and description of the recommanded therapy | A description will be done of therapie(s) recommanded and/or received by patients based on recommandation done by the Molecular Tumor Board after reviewing of molecular profil | at least 3 years after patient enrollment | 
| Describe the clinical impact of this molecular profiling in term of PFS | Progression free survival for each recommanded therapies received | at least 3 years after patient enrollment | 
| Describe the clinical impact of this molecular profiling in term of OS | Overall survival for each recommanded therapies received | at least 3 years after patient enrollment | 
| Describe the clinical impact of this molecular profiling in term of tumor response | Tumoral response (clinic and/or radiologic) for each recommanded therapies received | at least 3 years after patient enrollment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
all advanced malignant tumor