Biomarkers for Neoadjuvant Pembrolizumab in Non-Metastatic Prostate Cancer Positive by 18FDG-PET Scanning (PICT-01)
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|ClinicalTrials.gov Identifier: NCT04009967|
Recruitment Status : Recruiting
First Posted : July 8, 2019
Last Update Posted : March 20, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: Pembrolizumab||Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Clinical and Translational Study of Neoadjuvant Pembrolizumab Before Radical Prostatectomy in Non-metastatic Gleason ≥8 Prostate Cancer Patients Positive by 18FDG-PET Scanning ( PICT-01)|
|Actual Study Start Date :||January 10, 2020|
|Estimated Primary Completion Date :||November 1, 2021|
|Estimated Study Completion Date :||November 30, 2022|
Experimental: Prostate Cancer
Participants will receive 3 cycles of pembrolizumab regardless of PD-L1 status. After completion of the second cycle of pembrolizumab treatment, and just before the third injection of pembrolizumab an 18FDG-PET/CT scan will be performed to assess a potential metabolic response. Then between 2 to 4 weeks after the third treatment, subjects will undergo radical prostatectomy. Subjects will be followed every 3 months during the first year post-surgery and according to physician decision during the following years.
Pembrolizumab 200 mg every three weeks for 3 cycles only
Other Name: Keytruda
- The antitumor activity of pembrolizumab assessed as the tumor response rate based on the change in tumor volume as measured by 18FDG-PET [ Time Frame: Through study completion, an average of 1 year ]The change in tumor volume will be assessed by change in tumor volume from baseline after 3 cycles of pembrolizumab treatment
- Mean difference change in proliferative index in prostate cancer patients between patients treated with pembrolizumab and the control cohort [ Time Frame: Through study completion, an average of 1 year ]Proliferative index is measured by Ki67/apoptosis rate
- Immune cell infiltration and immune checkpoint expression [ Time Frame: Through study completion, an average of 1 year ]Compare large panel of ICP (Immune CheckPoints) ligand expression between patients treated by pembrolizumab and cohort control by imaging mass cytometry
- One year PSA (Prostate Specific Antigen) failure rate [ Time Frame: At the end of study completion, an average of 3 years ]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.
- 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. [ Time Frame: At the end of study completion, an average of 3 years ]dMMR and MSI-H status will be determined by immunochemistry and PCR (Polymerase Chain Reaction) respectively
- Assess the expression of a series of cytokines and eicosanoids [ Time Frame: At the end of study completion, an average of 3 years ]The concentration of 27 cytokines and 37 eicosanoids in tumor sample will be evaluated
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04009967
|Contact: Alain Bergeron, Ph.D||418-525-4444 ext 15530||Alain.Bergeron@crchudequebec.ulaval.ca|
|Contact: Marjorie Besançon, Ph.D||418-525-4444 ext email@example.com|
|CHU de Québec-Université Laval||Recruiting|
|Contact: Yves Fradet, MD 418 525-4444 ext 15555 firstname.lastname@example.org|
|Contact: Marjorie Besançon, PhD 418 525-4444 ext 20417 email@example.com|
|Principal Investigator: Yves Fradet, MD|
|Principal Investigator:||Yves Fradet, MD||CHU de Québec-Université Laval|