Intrinsic Validity of Molecular Marker(s) Detection on Tissular Tumoral DNA to Predict the Efficacy of 177Lutetium-PSMA-617 (Lu-PSMA) Treatment for Castration-resistant Metastatic Prostate Cancer (PSMA-PRED)
Overview
- Phase
- N/A
- Intervention
- Blood samples
- Conditions
- Castration-resistant Metastatic Prostate Cancer
- Sponsor
- Centre Jean Perrin
- Enrollment
- 120
- Locations
- 5
- Primary Endpoint
- Molecular abnormalities retained on primary tumor sample predicting response to Lu-PSMA in metastatic castration resistant prostate cancer patients assessed according to RECIST 1.1 and/or PCWG3 criteria
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
Prostate cancer is the most common cancer in men. Its incidence is rising as the population ages. In the localized stage, the 5-year overall survival rate (OS) is 98%. Metastatic progression and resistance to castration have a negative impact on prognosis. Despite recent advances in management, the 5-year OS is around 30%. Therapeutic advances in this indication have been made mainly by the use of taxanes and second-generation hormone therapy. These treatments have improved OS and progression-free survival (PFS). They are now used as standard therapy.
More recently, the Phase III VISION trial confirmed the improvement in OS and radiological PFS achieved by treatment with the radioligand 177Lutetium-PSMA-617 (Lu-PSMA) in patients with advanced metastatic castration-resistant prostate cancer (mCRPC).
This treatment is currently available in early access in France. Despite encouraging results, 40% of patients will not respond to Lu-PSMA, and there are currently no validated predictive factors. Studies are currently on going, but the identification of biomarkers seems necessary to better stratify risk in these patients.
Numerous tissue prognostic tests based on molecular characteristics or cell proliferation are emerging with this in mind. At present, molecular profiling is not a routine technique for prostate cancer, as it is for other solid cancers. At an early stage, the Decipher® Genomic classification tool has shown prognostic utility independently of therapeutic and clinico-pathological data.
According to recent studies, methylome analysis would enable the subdivision of mCRPCs and could help identify new therapeutic targets.
In the metastatic phase, certain molecular abnormalities involving DNA repair genes are predictive of response to PARP inhibitors.
Molecular analysis (mutations, copy number alterations, gene expression, DNA methylation) could therefore be useful in optimizing the management of mCRPC patients treated with Lu-PSMA.
If reliable molecular abnormalities are identified on tissue, a diagnostic technique based on circulating tumor DNA (ctDNA) analysis will be useful in decision-making for these patients. A biological collection will therefore be created during the course of this study, with a view to using ctDNA analysis in subsequent research.
Detailed Description
Prostate cancer is the most common cancer in men. Its incidence is rising as the population ages. In the localized stage, the 5-year overall survival rate (OS) is 98%. Metastatic progression and resistance to castration have a negative impact on prognosis. Despite recent advances in management, the 5-year OS is around 30%. Therapeutic advances in this indication have been made mainly by the use of taxanes and second-generation hormone therapy. These treatments have improved OS and progression-free survival (PFS). They are now used as standard therapy. More recently, the Phase III VISION trial confirmed the improvement in OS and radiological PFS achieved by treatment with the radioligand 177Lutetium-PSMA-617 (Lu-PSMA) in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). This treatment is currently available in early access in France. Despite encouraging results, 40% of patients will not respond to Lu-PSMA, and there are currently no validated predictive factors. Studies are currently on going, but the identification of biomarkers seems necessary to better stratify risk in these patients. Numerous tissue prognostic tests based on molecular characteristics or cell proliferation are emerging with this in mind. At present, molecular profiling is not a routine technique for prostate cancer, as it is for other solid cancers. At an early stage, the Decipher® Genomic classification tool has shown prognostic utility independently of therapeutic and clinico-pathological data. According to recent studies, methylome analysis would enable the subdivision of mCRPCs and could help identify new therapeutic targets. In the metastatic phase, certain molecular abnormalities involving DNA repair genes are predictive of response to PARP inhibitors. Molecular analysis (mutations, copy number alterations, gene expression, DNA methylation) could therefore be useful in optimizing the management of mCRPC patients treated with Lu-PSMA. If reliable molecular abnormalities are identified on tissue, a diagnostic technique based on circulating tumor DNA (ctDNA) analysis will be useful in decision-making for these patients. A biological collection will therefore be created during the course of this study, with a view to using ctDNA analysis in subsequent research. This is an interventional, multi-center study. The study is prospective, single-arm, open-label and non-randomized. Its primary objective is to identify biomarkers of interest, in primary tissue, predictive of response to Lu-PSMA treatment in patients with mCRPC, through the detection of molecular abnormalities in DNA/RNA and methyloma.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male \>18 years of age
- •Patient with histologically confirmed of metastatic castration resistant prostatic adenocarcinoma and with tumor biological material available (prostatic biopsies or prostatectomy)
- •Patient who received at least one taxane line and a second generation hormone therapy line
- •Patient receiving androgen deprivation therapy with serum testosterone \< 50 ng/dL or \< 1.7 nmol/L or having undergone surgical castration
- •Progressive mCRPC based based on at least 1 of the following criteria :
- •Serum or plasma PSA progression defined as 2 consecutive increases in PSA measured at least 1 week prior. The minimal start value is 2.0 ng/mL ; 1,0 ng/mL is the minimal start value if confirmed increase in PSA is the only indication of progress
- •Soft-tissue progression by RECIST 1.1 criteria
- •Progression of bone disease : two new lesions ; only the positivity of bone scan defines metastatic bone disease, according to PCWG3 criteria.
- •Patients with at least one metastasis, bone and/or soft tissue and/or visceral, documented by the following methods in the 43 days prior to inclusion :
- •Bone metastasis (regardless of location) highlighted by bone scan AND/OR
Exclusion Criteria
- Not provided
Arms & Interventions
Interventional
Genetic analysis will be conducted on intial tumor sample in order to identify biomarkers
Intervention: Blood samples
Outcomes
Primary Outcomes
Molecular abnormalities retained on primary tumor sample predicting response to Lu-PSMA in metastatic castration resistant prostate cancer patients assessed according to RECIST 1.1 and/or PCWG3 criteria
Time Frame: From enrollment to 24 months after Lu-PSMA treatment
Biological interpretation and response to Lu-PSMA treatment on bone scan and CT scan according to RECIST 1.1 and/or PCWG3 criteria
Secondary Outcomes
- Correlation between biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and survival without radiological progression(From enrollment to 24 months after Lu-PSMA treatment)
- Correlation between biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and overall survival(From enrollement to the end of the study, up to 58 months)
- Correlation between biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and survival without biological progression(From enrollment to 24 months after Lu-PSMA treatment)
- Correlation between biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and survival without clinical progression(From enrollment to 24 months after Lu-PSMA treatment)
- Assess whether consideration of clinical characteristics improves biomarker performance(From enrollement to end of Lu-PSMA treatment, up to 58 months)
- Assess whether consideration of radiological characteristics improves biomarker performance(From enrollement to end of Lu-PSMA treatment, up to 58 months)
- Correlation between the biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and adverse effects during treatment.(From enrollment to the end of Lu-PSMA treatment, up to 58 months)
- Assess whether consideration of biological characteristics improves biomarker performance(From enrollement to end of Lu-PSMA treatment, up to 58 months)
- Biological interpretation and response to Lu-PSMA treatment on PET scan(From enrollment to 24 months after Lu-PSMA treatment)