Ignite Creation Date:
2024-05-06 @ 9:40 AM
Last Modification Date:
2024-10-26 @ 12:17 PM
Study NCT ID:
NCT03040791
Status:
UNKNOWN
Last Update Posted:
2021-08-26
First Post:
2017-01-27
Brief Title:
Nivolumab in Prostate Cancer With DNA Repair Defects ImmunoProst Trial
Sponsor:
Hospital Moinhos de Vento
Organization:
Hospital Moinhos de Vento
Study Overview
Official Title:
Nivolumab in Prostate Cancer With DNA Repair Defects ImmunoProst Trial
Status:
UNKNOWN
Status Verified Date:
2021-08
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ImmunoProst
Brief Summary:
Prostate Cancer PC is the most frequent cancer in men accounting for 21 of new cases of cancer in men in the United States Among the four most incident tumors breast lung and colorectal cancer prostate cancer is the only that does not have any predictive biomarker to guide the treatment Even though the molecular heterogeneity of PC is well-documented treatment has not been molecularly stratified and the need for genetic prognostic and predictive markers is critical
DNA repair defects DRD mainly in the Homologous Recombination HR pathway such as BRCA1 BRCA2 ATM and CHEK2 are emerging as potential biomarkers in prostate cancer It is well known BRCA1 and BRCA2 carriers have better Progression-Free Survival PFS and Overall Survival OS than non-carriers in ovarian cancer Differently than ovarian tumors that BRCA mutations provides a good prognosis PC patients who harbor HR defects have a higher Gleason score 6 an increased risk of recurrence and poor prognosis The predictive role of DRD in PC was demonstrated in a recent trial using Olaparib a PARP inhibitor in DRD carriers This trial showed 88 of response rate with Olaparib a PARP inhibitor that acts in HR pathway by synthetic lethality
Recent data demonstrated important association between HR deficient high-grade serous ovarian cancer HGSOC high neoantigen load and high expression of PD-1PD-L1 compared with HR proficient HGSOCs 10 This study showed that BRCA1 and BRCA2 mutations increase the number of tumor-infiltrating lymphocytes TILs and confer a better prognosis The unprecedented success of immunotherapy in malignant disorders has provided evidence that the patients immune system can be improved to attack established tumors mainly melanoma non-small cell lung cancer and kidney cancer A high mutational burden increases the likelihood of the development of specific neoepitopes that would confer clinical benefit from CTLA-4 and PD-1 blockade
These data showed that specific DNA repair defects increase the mutational burden the expression of PD-1PD-L1 and TILs and could improve the response to immunotherapy in cancer This rationale was already tested in a trial that evaluated the PD-1 checkpoint inhibitor Pembrolizumab in mismatch-repair deficient patients a kind of DNA repair defect by definition This important trial showed that this DRD predicted clinical benefit of immune checkpoint blockade in many types of cancer especially colorectal cancer
DNA repair defects DRD mainly in the Homologous Recombination HR pathway such as BRCA1 BRCA2 ATM and CHEK2 are emerging as potential biomarkers in prostate cancer It is well known BRCA1 and BRCA2 carriers have better Progression-Free Survival PFS and Overall Survival OS than non-carriers in ovarian cancer Differently than ovarian tumors that BRCA mutations provides a good prognosis PC patients who harbor HR defects have a higher Gleason score 6 an increased risk of recurrence and poor prognosis The predictive role of DRD in PC was demonstrated in a recent trial using Olaparib a PARP inhibitor in DRD carriers This trial showed 88 of response rate with Olaparib a PARP inhibitor that acts in HR pathway by synthetic lethality
Recent data demonstrated important association between HR deficient high-grade serous ovarian cancer HGSOC high neoantigen load and high expression of PD-1PD-L1 compared with HR proficient HGSOCs 10 This study showed that BRCA1 and BRCA2 mutations increase the number of tumor-infiltrating lymphocytes TILs and confer a better prognosis The unprecedented success of immunotherapy in malignant disorders has provided evidence that the patients immune system can be improved to attack established tumors mainly melanoma non-small cell lung cancer and kidney cancer A high mutational burden increases the likelihood of the development of specific neoepitopes that would confer clinical benefit from CTLA-4 and PD-1 blockade
These data showed that specific DNA repair defects increase the mutational burden the expression of PD-1PD-L1 and TILs and could improve the response to immunotherapy in cancer This rationale was already tested in a trial that evaluated the PD-1 checkpoint inhibitor Pembrolizumab in mismatch-repair deficient patients a kind of DNA repair defect by definition This important trial showed that this DRD predicted clinical benefit of immune checkpoint blockade in many types of cancer especially colorectal cancer
Detailed Description:
This is a Phase II two-stage multi-center single-arm and open-label trial of Nivolumab BMS-936558 in patients with metastatic castration-resistant prostate cancer mCRPC who have progressed to a taxane-based chemotherapy regimen previously Eligible patients must have ECOG 0-2 and material for biomarker analysis Prior enzalutamide abiraterone and cabazitaxel are permitted but not necessary to enrollment The germline and somatic DRD BRCA1 BRCA2 ATM PTEN CHEK2 RAD51C RAD51D PALB2 MLH1 MSH2 MSH6 PMS2 will be assessed by T-NGS of metastatic sites or by liquid biopsy The primary endpoint is PSA 50 response rate PSA50 following the Prostate Cancer Working Group 3 criteria The trial will meet its endpoint if 329 men achieve a PSA50 response The secondary endpoints will include progression-free survival PFS overall survival radiologic PFS PSA response rate at 6 and 12 months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None