Urologic CancerPhase 2Pembro-SRTNCT04931979
SRT in Combination With Pembrolizumab in Patients With Recurrent Prostate Cancer After Radical Prostatectomy
A Phase 2 study testing Pembrolizumab Injection [Keytruda] and Salvage Radiation Therapy (SRT) in people with Urologic Cancer and Biochemical Recurrence of Malignant Neoplasm of Prostate, run by Prof. Dr. med. Christian Gratzke at 1 site in Germany.
Trial summary
To evaluate the efficacy and safety of a pembrolizumab therapy of pembrolizumab in combination with standard salvage radiation therapy (SRT) in patients with biochemical recurrence (BCR) of prostate-specific antigen (PSA) persistence after radical prostatectomy (RP). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Urologic Cancer, Biochemical Recurrence of Malignant Neoplasm of Prostate
- What is being tested?
- Pembrolizumab Injection [Keytruda] and Salvage Radiation Therapy (SRT)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteGermany
- Study dates
- 20 Oct 2022to 1 Apr 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male patients who are at least 18 years of age on the day of signing informed consent
- Histologically confirmed diagnosis of an adenocarcinoma of the prostate and a BCR or PSA persistence after RP
- Histology of the RP specimen needs to fulfill the following criteria: adenocarcinoma of the prostate, Gleason score 7-10; pNX or pN0 or pN1 (max. 2 lymph nodes involved)
- Imaging within 50 days prior to study inclusion is mandatory (patient registration) ([68Ga] or [18F] PSMA PET-CT as standard imaging modality, alternatively CT abdomen and full-body bone scan)
- PSA value between ≥0.2 and ≤1.0 ng/ml measured at least six weeks postoperatively
- The patients agree not to undergo testicular sperm extraction for at least 90 days after the last administration of pembrolizumab. (Due to prior surgical removal of the prostate no contraception is necessary.)
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- Written informed consent obtained according to international guidelines and local law
- Patients further having an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Patients with adequate organ function as defined in clinical trial protocol (CTP) (Section 4)
Who cannot join
- Prior-therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
- Prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to registration (like neo-adjuvant androgen deprivation therapy (ADT), secondary hormone ablation or taxan-based chemotherapy).
- Prior radiotherapy within 4 weeks before start of study medication. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- Distant metastases or suspicious lymph nodes outside the lower pelvis in imaging with PSMA PET-CT are to be excluded (patients with PET positive bone lesions that are morphologically not clearly suspicious of metastases and would not change clinical practice can be included).
- Adverse histology of RP specimen (e.g. neuroendocrine or small cell)
- Any vaccination with live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study medication. Administration of killed vaccines is allowed.
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- Currently or previously participating in a study of an investigational product within 4 weeks prior to the first dose of study medication.
- Diagnosis of immunodeficiency, chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication.
- History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Active autoimmune disease that required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
- History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or currently pneumonitis/ interstitial lung disease
- Active infection requiring systemic therapy.
- History of Human Immunodeficiency Virus (HIV) infection.
- History of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as Hepatitis C virus (HCV) RNA is detected) infection. No testing is required.
- History of active TB (Bacillus Tuberculosis).
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the investigator.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- History of allogeneic tissue/solid organ transplantation.
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Clinic of Urology, Medical Center - University of Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Markus T Grabbert, Dr. med., +49 761 270 28930, markus.grabbert@uniklinik-freiburg.de
Anika Josef, Dr. phil., +49 761 270 77110, anika.josef@uniklinik-freiburg.de
About this study
Official title: Radiotherapy in Combination With Pembrolizumab in Patients With PSA Persistence or Biochemical Recurrence After Radical Prostatectomy Due to Prostate Cancer
To evaluate the efficacy and safety of a pembrolizumab therapy of pembrolizumab in combination with standard salvage radiation therapy (SRT) in patients with biochemical recurrence (BCR) of prostate-specific antigen (PSA) persistence after radical prostatectomy (RP).
Read the detailed description
Current guidelines recommend a salvage radiation therapy (SRT) with at least 66 Gy as preferred treatment option in patients with biochemical recurrence (BCR) resp. PSA (prostate-specific antigen) persistence after radical prostatectomy (RP). The guideline recommendation is based on two non-randomized controlled trials that showed an improved cancer-specific survival and a better local tumor control. The optimal timing for a radiation therapy cannot be clearly defined by the available literature. A radiation therapy as early as possible with a PSA level <0,5 ng/ml seems to be beneficial. The guideline recommendation is based on two non-randomized controlled trials that showed an improved cancer-specific survival and a better local tumor control. A complete biochemical response is to be expected in approx. 60-70% of patients after 12 months.
The established imaging modality in patients with BCR used to be computed tomography of the abdomen and bone scintigraphy for the detection of skeletal lesions. The introduction of PSMA PET/CT (prostate-specific membrane antigen positron emission tomography combined with CT) has changed the imaging in patients with recurrent prostate cancer and several studies could show improved oncological results compared to patients undergoing standard treatment without positron emission tomography (PET) positive lesions with a 10% improvement in biochemical recurrence-free survival after 2 years.
Immunotherapy alone has not yet proven to be efficacious in prostate cancer as a monotherapy in smaller studies. Several trials could show that the combination of the immunotherapy and radiation therapy has the potential to provide a synergistic effect in treating genitourinary malignancies, whereas more studies are needed to uncover the exact underlying mechanism. In brief, radiation therapy of the location of recurrence increases the tumor´s immunogenic potential and a systemic immunological reaction is initiated that leads to an increased activity of the immune system against tumor tissue (abscopal effect). Lately several trials have been evaluating a possible synergistic effect with tolerable side-effects. A trial combining those two treatment regimens in the early treatment of prostate cancer recurrence is not available up to date.
The clinical benefit of concomitant androgen deprivation therapy (ADT) is controversial and literature failed to show a clear overall survival benefit for all patients. Several retrospective trials have been evaluating a concomitant ADT and for patients with risk factors like suspicious lymph-nodes in staging diagnostics. Several studies have been evaluating the effect of concomitant ADT though. Shipley et al. could show the addition of 24 months of bicalutamide to SRT resulted in significantly higher rates of long-term overall survival. However, sub-group analyses revealed that this effect counts mainly for patients with PSA of >0.7 ng/ml before SRT. The GETUG-AFU trial did not find any survival benefit for short term (6 months) ADT additionally to SRT. However, a significant benefit in progression-free survival after 120 months of follow-up time was reported. A combination therapy of pembrolizumab and radiation therapy has not been evaluated before in this patient population. The investigators hypothesize that this combination is more effective than radiation therapy alone due to a radiogenic triggered immunomodulation which increases the anti-tumor effect of pembrolizumab. For patients with BCR or PSA persistence after RP no such treatment regimen has been tested yet.
- Being tested
- Pembrolizumab Injection [Keytruda], Salvage Radiation Therapy (SRT)
- Keywords
- urologic cancer, biochemical recurrence of prostate-specific antigen, radical prostatectomy, pembrolizumab
- Medical subject headings
- Urologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab Injection [Keytruda]Drug
Up to 17 cycles of pembrolizumab until disease progression, toxicity, death, or withdrawal of IC (whichever occurs first)
Salvage Radiation Therapy (SRT)Radiation
SRT according to standard of care (SRT with at least 66 Gy)
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Pembrolizumab 200mg i.v. three-weekly in combination with salvage radiation therapy (SRT) according to standard of care Receives: Drug: Pembrolizumab Injection [Keytruda]; Radiation: Salvage Radiation Therapy (SRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete biochemical response
number of patients with complete biochemical response defined as a PSA level below limit of detection.
Patients will be counted as a responder with respect to the primary endpoint, if the PSA level is below the limit of detection at week 60 (± 2 weeks) after start of trial treatment. Patients will be counted as a non-responder with respect to the primary endpoint, if the PSA level is above the limit of detection at week 60 (± 2 weeks).
Measured: at week 60 (+/- weeks) after start of treatment
Secondary outcomes (1)
Radiographic progression-free survival
The probability of radiographic progession-free survival at week 60 (+/- 2 weeks) after start of treatment will be estimated as the number of patients who are alive and progression-free divided by the total number of treated patients.
Measured: at week 60 (+/- 2 weeks) after start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2021
- Study start20 Oct 2022
- Primary completion1 Jul 2025 (estimated)
- Study completion1 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urologic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The trial is designed as a phase II, open-label, monocentric, single-arm trial evaluating a combination therapy of pembrolizumab and salvage radiation therapy (SRT) in patients with biochemical recurrence (BCR) or persisting prostate-specific antigen (PSA) after radical prostatectomy (RP).
- Masking
- None (open label)
- Enrolment
- 49 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prof. Dr. med. Christian Gratzke
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Prof. Dr. med. Christian Gratzke, University Hospital Freiburg
- Investigators
- Christian Gratzke, Prof. Dr., Principal investigator, University Medical Center - University of Freiburg, Clinical of Urology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04931979
- Sponsor's protocol ID
- MK-3475-C51
- Other IDs
- 2021-001291-42, P003141
- Acronym
- Pembro-SRT
- Status last verified
- Nov 2022
- First submitted
- 19 Apr 2021
- Last updated
- 1 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiotherapy in Combination With Pembrolizumab in Patients With PSA Persistence or Biochemical Recurrence After Radical Prostatectomy Due to Prostate Cancer
- ClinicalTrials.gov ID
- NCT04931979
- Acronym / sponsor ID
- Pembro-SRT / MK-3475-C51
- Keywords
- urologic cancer, biochemical recurrence of prostate-specific antigen, radical prostatectomy, pembrolizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 49 participants (estimated)
- Lead sponsor
- Prof. Dr. med. Christian GratzkeUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 20 Oct 2022 (actual)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 1 Apr 2026 (estimated)
- First posted
- 18 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the efficacy and safety of a pembrolizumab therapy of pembrolizumab in combination with standard salvage radiation therapy (SRT) in patients with biochemical recurrence (BCR) of prostate-specific antigen (PSA) persistence after radical prostatectomy (RP).
Detailed description
Current guidelines recommend a salvage radiation therapy (SRT) with at least 66 Gy as preferred treatment option in patients with biochemical recurrence (BCR) resp. PSA (prostate-specific antigen) persistence after radical prostatectomy (RP). The guideline recommendation is based on two non-randomized controlled trials that showed an improved cancer-specific survival and a better local tumor control. The optimal timing for a radiation therapy cannot be clearly defined by the available literature. A radiation therapy as early as possible with a PSA level <0,5 ng/ml seems to be beneficial. The guideline recommendation is based on two non-randomized controlled trials that showed an improved cancer-specific survival and a better local tumor control. A complete biochemical response is to be expected in approx. 60-70% of patients after 12 months.
The established imaging modality in patients with BCR used to be computed tomography of the abdomen and bone scintigraphy for the detection of skeletal lesions. The introduction of PSMA PET/CT (prostate-specific membrane antigen positron emission tomography combined with CT) has changed the imaging in patients with recurrent prostate cancer and several studies could show improved oncological results compared to patients undergoing standard treatment without positron emission tomography (PET) positive lesions with a 10% improvement in biochemical recurrence-free survival after 2 years.
Immunotherapy alone has not yet proven to be efficacious in prostate cancer as a monotherapy in smaller studies. Several trials could show that the combination of the immunotherapy and radiation therapy has the potential to provide a synergistic effect in treating genitourinary malignancies, whereas more studies are needed to uncover the exact underlying mechanism. In brief, radiation therapy of the location of recurrence increases the tumor´s immunogenic potential and a systemic immunological reaction is initiated that leads to an increased activity of the immune system against tumor tissue (abscopal effect). Lately several trials have been evaluating a possible synergistic effect with tolerable side-effects. A trial combining those two treatment regimens in the early treatment of prostate cancer recurrence is not available up to date.
The clinical benefit of concomitant androgen deprivation therapy (ADT) is controversial and literature failed to show a clear overall survival benefit for all patients. Several retrospective trials have been evaluating a concomitant ADT and for patients with risk factors like suspicious lymph-nodes in staging diagnostics. Several studies have been evaluating the effect of concomitant ADT though. Shipley et al. could show the addition of 24 months of bicalutamide to SRT resulted in significantly higher rates of long-term overall survival. However, sub-group analyses revealed that this effect counts mainly for patients with PSA of >0.7 ng/ml before SRT. The GETUG-AFU trial did not find any survival benefit for short term (6 months) ADT additionally to SRT. However, a significant benefit in progression-free survival after 120 months of follow-up time was reported. A combination therapy of pembrolizumab and radiation therapy has not been evaluated before in this patient population. The investigators hypothesize that this combination is more effective than radiation therapy alone due to a radiogenic triggered immunomodulation which increases the anti-tumor effect of pembrolizumab. For patients with BCR or PSA persistence after RP no such treatment regimen has been tested yet.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The trial is designed as a phase II, open-label, monocentric, single-arm trial evaluating a combination therapy of pembrolizumab and salvage radiation therapy (SRT) in patients with biochemical recurrence (BCR) or persisting prostate-specific antigen (PSA) after radical prostatectomy (RP).
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Pembrolizumab Injection [Keytruda], Radiation: Salvage Radiation Therapy (SRT)Pembrolizumab 200mg i.v. three-weekly in combination with salvage radiation therapy (SRT) according to standard of care |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male patients who are at least 18 years of age on the day of signing informed consent
- Histologically confirmed diagnosis of an adenocarcinoma of the prostate and a BCR or PSA persistence after RP
- Histology of the RP specimen needs to fulfill the following criteria: adenocarcinoma of the prostate, Gleason score 7-10; pNX or pN0 or pN1 (max. 2 lymph nodes involved)
- Imaging within 50 days prior to study inclusion is mandatory (patient registration) ([68Ga] or [18F] PSMA PET-CT as standard imaging modality, alternatively CT abdomen and full-body bone scan)
- PSA value between ≥0.2 and ≤1.0 ng/ml measured at least six weeks postoperatively
Key exclusion criteria (20 listed)
- Prior-therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
- Prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to registration (like neo-adjuvant androgen deprivation therapy (ADT), secondary hormone ablation or taxan-based chemotherapy).
- Prior radiotherapy within 4 weeks before start of study medication. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- Distant metastases or suspicious lymph nodes outside the lower pelvis in imaging with PSMA PET-CT are to be excluded (patients with PET positive bone lesions that are morphologically not clearly suspicious of metastases and would not change clinical practice can be included).
- Adverse histology of RP specimen (e.g. neuroendocrine or small cell)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab Injection [Keytruda]Up to 17 cycles of pembrolizumab until disease progression, toxicity, death, or withdrawal of IC (whichever occurs first) | Drug | Treatment |
| Salvage Radiation Therapy (SRT)SRT according to standard of care (SRT with at least 66 Gy) | Radiation | Treatment |
Primary outcome
Complete biochemical response
Time frame: at week 60 (+/- weeks) after start of treatment
number of patients with complete biochemical response defined as a PSA level below limit of detection. Patients will be counted as a responder with respect to the primary endpoint, if the PSA level is below the limit of detection at week 60 (± 2 weeks) after start of trial treatment. Patients will be counted as a non-responder with respect to the primary endpoint, if the PSA level is above the limit of detection at week 60 (± 2 weeks).
1 secondary outcome
Radiographic progression-free survival
Time frame: at week 60 (+/- 2 weeks) after start of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian Gratzke, Prof. Dr. principal investigator
University Medical Center - University of Freiburg, Clinical of Urology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab Injection [Keytruda] and Salvage Radiation Therapy (SRT) in people with Urologic Cancer and Biochemical Recurrence of Malignant Neoplasm of Prostate, run by Prof. Dr. med. Christian Gratzke at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Markus T Grabbert, Dr. (+49 761 270 28930, markus.grabbert@uniklinik-freiburg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete biochemical response (time frame: at week 60 (+/- weeks) after start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2023.