Various approaches are currently being developed for prostate cancer immunotherapy. However, a major challenge facing the development of cancer immunotherapy is the identification of tumors that would best respond to this type of treatment. Different studies suggest that prostate cancer more likely to progress are more infiltrated by exhausted T cells expressing the cell surface protein PD1 (Programmed cell death 1). Therefore, there is a strong rationale for selecting patients at higher risk of progression for testing the efficacy of anti-PD1 therapy. High glucose metabolism as detected by fludeoxyglucose F18 (FDG)-positron emission tomography (PET) (18FDG-PET) imagery is an innovative biological biomarker-based method to identify patients at higher risk of recurrence and early failure to hormonotherapy. Recent study demonstrated that high intra-prostatic 18-FDG-uptake was associated with higher Gleason grades. Therefore the one third of Gleason ≥ 8 prostate cancer patients with higher 18FDG uptake would be ideal candidates for early immunotherapy treatments based on anti-PD-1 such as pembrolizumab. The study aimed to identify biomarkers predictive the response to Pembrolizumab given prior to radical prostatectomy in participants with primary prostate cancer at high risk of progression.
This is a Phase II, single-arm and open-label trial of pembrolizumab (MK-3475) in localized prostate cancer patients with newly diagnosed non-metastatic prostate cancer (Gleason grade ≥8 on biopsy) with positive tumor by FDG-PET (SUV max \>4) who chose to undergo radical prostatectomy and lymph node dissection as primary treatment. The trial will meet its endpoint if a reduction in cancer extent, proliferative index and increased apoptosis, as well as an induction of favorable immune cell infiltration and immune checkpoint expression profiles are observed after treatment compare to baseline..
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Pembrolizumab 200 mg every three weeks for 3 cycles only
CHU de Québec-Université Laval
Québec, Canada
The antitumor activity of pembrolizumab assessed as the tumor response rate based on the change in tumor volume as measured by 18FDG-PET
The change in tumor volume will be assessed by change in tumor volume from baseline after 3 cycles of pembrolizumab treatment
Time frame: Through study completion, an average of 1 year
Mean difference change in proliferative index in prostate cancer patients between patients treated with pembrolizumab and the control cohort
Proliferative index is measured by Ki67/apoptosis rate
Time frame: Through study completion, an average of 1 year
Immune cell infiltration and immune checkpoint expression
Compare large panel of ICP (Immune CheckPoints) ligand expression between patients treated by pembrolizumab and cohort control by imaging mass cytometry
Time frame: Through study completion, an average of 1 year
One year PSA (Prostate Specific Antigen) failure rate
A statistically significant difference in the 1 year PSA failure rate compared to a historical cohort of untreated patients will indicate that the study has met this secondary objective.
Time frame: At the end of study completion, an average of 3 years
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.0
Time frame: Through study completion, an average of 2 years
Number of participants with decrease in SUV uptake after 3 cycles of pembrolizumab
Time frame: Through study completion, an average of 2 years
Assess a possible correlation between deficient mismatched repair (dMMR) and microsatellite instability-high (MSI-H) and response to pembrolizumab.
dMMR and MSI-H status will be determined by immunochemistry and PCR (Polymerase Chain Reaction) respectively
Time frame: At the end of study completion, an average of 3 years
Assess the expression of a series of cytokines and eicosanoids
The concentration of 27 cytokines and 37 eicosanoids in tumor sample will be evaluated
Time frame: At the end of study completion, an average of 3 years
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