The proposal is to conduct a prospective, multi-cohort study aiming to decipher molecular profiles/biological characteristics of advanced cancer patients during the course of their disease with longitudinal and sequential analyses of tumor and liquid biopsies. This approach will allow i) to develop a model in order to predict tumor response / resistance in real life conditions and to better understand adaptive mechanisms and ii) to potentially propose therapeutic options to enrolled patients following the review of the biological/molecular data generated during this study and during a Molecular Tumor Board in case of disease progression. This study will include 12 cohorts according to tumor type and standard treatment received (See Inclusion criteria I1). Patient will be enrolled before the initiation of standard anti-cancer treatment.
Most of the molecular screening programs have allowed to successfully guide patients to personalized therapy only for a minority of patients (10-20%) and few patients have actually benefit from these programs with low objective response under personalized therapy. During the course of disease and / or of treatment, tumors become more heterogeneous and include a collection of cells harboring distinct molecular signatures with differential levels of sensitivity to treatment. Assessment of tumor heterogeneity and plasticity are essential for the development of effective therapies. Longitudinal analysis of biopsy samples is of considerable interest to assess the complex clonal architecture of cancers and potentially adapt cancer treatment to tumor profile/characteristics overtime. In this context, profiling of circulating tumor DNA using non-invasive liquid biopsies is also an interesting approach to assess cancer evolution by showing the contribution of clonal heterogeneity to chemotherapy resistance and metastasis in high-risk patients. The proposal is to conduct a prospective, multi-cohort study aiming to decipher molecular profiles/biological characteristics of advanced cancer patients during the course of their disease with longitudinal and sequential analyses of tumor and liquid biopsies. This approach will allow i) to develop a model in order to predict tumor response / resistance in real life conditions and to better understand adaptive mechanisms and ii) to potentially propose therapeutic options to enrolled patients following the review of the biological/molecular data generated during this study and during a Molecular Tumor Board in case of disease progression. This study will include 12 cohorts according to tumor type and standard treatment received (See Inclusion criteria I1). Patient will be enrolled before the initiation of standard anti-cancer treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
500
Longitudinal molecular profiling of tumor and liquid biopsies.
HOPITAL Pierre WERTHEIMER - HCL
Bron, France
NOT_YET_RECRUITINGCentre Léon Bérard
Lyon, France
RECRUITINGNumber of patients with meaningful molecular genetic alterations on tumor sample
Identification of molecular genetic alterations based on molecular characterisation (WES and RNASeq) of tumor at diagnosis, then under standard anti-cancer treatment : treatment start, 1st radiological evaluation and disease progression
Time frame: At the end of study (4 years)
Number of patients with meaningful molecular genetic alterations on circulating tumour DNA (ctDNA)
Identification of molecular genetic alterations based on molecular characterisation (WES and RNASeq) of ctDNA under standard anti-cancer treatment : treatment start, each radiological evaluation and disease progression
Time frame: At the end of study (4 years)
Number of patients with meaningful immunological features
Identification and characterisation of the tumor microenvironment and the host's immunological profile, at diagnosis and during patient treatment
Time frame: At the end of study (4 years)
Objective Response Rate (ORR) as per RECIST V1.1 and according to central review
For solid tumors excluding glioblastoma only
Time frame: 3 months
Progression-Free Survival (PFS)
For glioblastoma only
Time frame: 6 months
Objective Response Rate (ORR) according to iwCLL criteria
For chronic lymphocytic leukemia
Time frame: 6 months
Correlation between disease evolution and molecular and/or immunological biomarkers
To identify potential prognostic and predictive biomarkers on tumor samples collected during patient's treatment and follow-up detected by molecular biology techniques, and on immunological findings
Time frame: Time Frame: up to 4 years
Evaluation of circulating-tumor DNA (ctDNA; liquid biopsy) yields similar genomic profile as the tumor sample.
To identify potential prognostic and predictive biomarkers based on changes on circulating tumour DNA (ctDNA), detected by molecular biology techniques
Time frame: 48 months
Number of patients with recommended therapy according to biological data (liquid versus tumor biopsy)
Time frame: 48 months
Tumor characteristics using a radiomic approach and detailed analyses of imaging.
Time frame: 48 months
FACT-G questionnaire
To evaluate the quality of life and emotional distress anxiety/depression over time of patients
Time frame: 48 months
HADS questionnaire
To evaluate the quality of life and emotional distress anxiety/depression over time of patients
Time frame: 48 months
PRO questionnaire
To evaluate the quality of life and emotional distress anxiety/depression over time of patients
Time frame: 48 months
Correlation between patient's understanding and experiences of precision medicine clinical trial
Measured by thematic analysis of semi-structured interviews: themes and sub-themes will be analyzed in order to develop items for the construction and validation of a quantitative questionnaire.
Time frame: 48 months
Correlation between socio-spatial inequalities in access to the PLANET program and the impact on the quality of life of patients
Questionnaire
Time frame: 48 months
TKI pharmacokinetics
Plasma concentrations of TKI
Time frame: 48 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.