Radiotherapy in combination with pembrolizumab in patients with PSA persistence or biochemical recurrence after radical prostatectomy due to prostate cancer - Pembro-SRT

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical Center - University Of Freiburg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

28 Oct 2022 → ongoing

Decision date (initial)

2024-08-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

MSD SHARP & DOME GmbH

External identifiers

EU CT number

2024-513633-20-00

EudraCT number

2021-001291-42

ClinicalTrials.gov

NCT04931979

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy and safety 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).

Conditions and MedDRA coding

recurrent prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Male patients who are at least 18 years of age on the day of signing informed consent.
2. 2. Histologically confirmed diagnosis of an adenocarcinoma of the prostate and a BCR or PSA persistence after RP.
3. 3. 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).
4. 4. Imaging within 50 days prior to study inclusion (patient registration) is mandatory ([68Ga] or [18F] PSMA PET-CT as standard imaging modality, alternatively CT abdomen and full-body bone scan).
5. 5. PSA value between ≥0.2 and ≤1.0 ng/ml measured at least six weeks postoperatively.
6. 6. 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.)
7. 7. Written informed consent obtained according to international guidelines and local law.
8. 8. Patients further having an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
9. 9. Patients with adequate organ function as defined in Table 2.

Exclusion criteria 20

1. 1. 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).
2. 2. 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 taxanbased chemotherapy).
3. 3. 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.
4. 4. Distant metastases or suspicious lymph nodes outside the lower pelvis in imaging with PSMA PET-CT (patients with PET positive bone lesions that are morphologically not clearly suspicious of metastases and would not change clinical practice can be included).
5. 5. Adverse histology of RP specimen (e.g. neuroendocrine or small cell)
6. 6. Any vaccination with live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study medication. Administration of killed vaccine is allowed.
7. 7. Currently or previously participating in a study of an investigational product within 4 weeks prior to the first dose of study medication.
8. 8. 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.
9. 9. History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
10. 10. Known active CNS metastases and/or carcinomatous meningitis.
11. 11. Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
12. 12. 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.
13. 13. History of (non-infectious) pneumonitis/intestinal lung disease that required steroids or currently pneumonitis/intestinal lung disease.
14. 14. Active infection requiring systemic therapy.
15. 15. History of Human Immunodeficiency Virus (HIV) infection.
16. 16. History of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection. No testing is required.
17. 17. History of active TB (Bacillus Tuberculosis).
18. 18. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the investigator.
19. 19. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
20. 20. History of allogeneic tissue/solid organ transplantation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. complete biochemical response defined as a PSA level below limit of detection at week 60 after start of pembrolizumab.

Secondary endpoints 6

1. radiographic progression-free survival (rPFS) at week 60 after start of pembrolizumab.
2. PSA-nadir level and time to PSA-nadir (TTN)
3. Pembrolizumab exposure: number of administered pembrolizumab doses
4. ADT: administered concomitant substances, duration, dosage (in high-risk patients only)
5. Time to initiation of subsequent therapy (secondary ADT or novel hormonal agents [NHA])
6. Functional assessment of cancer therapy - Prostate: FACT-P ver. 4.0 (www.facit.org)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical Center - University Of Freiburg

Sponsor organisation

Medical Center - University Of Freiburg

Address

Breisacher Strasse 153, Mooswald Mooswald

City

Freiburg Im Breisgau

Postcode

79110

Country

Germany

Scientific contact point

Organisation

Medical Center - University Of Freiburg

Contact name

Dr. med. Markus Tobias Grabbert

Public contact point

Organisation

Medical Center - University Of Freiburg

Contact name

Dr. med. Markus Tobias Grabbert

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications