SRT in Combination With Pembrolizumab in Patients With Recurrent Prostate Cancer After Radical Prostatectomy

NCT04931979 | Recruiting Phase 2 DMC

• 3 other identifiers: MK-3475-C512021-001291-42P003141
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Urologic Cancer; Biochemical Recurrence of Malignant Neoplasm of Prostate

Keywords

urologic cancer; biochemical recurrence of prostate-specific antigen; radical prostatectomy; pembrolizumab

Outcome Measures

Primary Outcomes (1)

• 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).

  at week 60 (+/- weeks) after start of treatment

Secondary Outcomes (1)

• Radiographic progression-free survival

  at week 60 (+/- 2 weeks) after start of treatment

Other Outcomes (12)

• PSA-nadir level

  lowest PSA level during pembrolizumab administration (49 weeks)

• Time to PSA-nadir (TNN)

  from start of trial treatment (visit 1/cycle 1) to lowest PSA level (up to 17 visits/ cycles of trial treatment during 49 weeks)

• Duration of pembrolizumab exposure

  from start of pembrolizumab administration (cycle 1/visit 1) to up to visit /cycle 17 during 49 weeks for each patient, each cycle is 21 days

Study Arms (1)

Treatment

EXPERIMENTAL

Pembrolizumab 200mg i.v. three-weekly in combination with salvage radiation therapy (SRT) according to standard of care

Drug: Pembrolizumab Injection [Keytruda]; Radiation: Salvage Radiation Therapy (SRT)

Interventions

Pembrolizumab Injection [Keytruda] DRUG

Up to 17 cycles of pembrolizumab until disease progression, toxicity, death, or withdrawal of IC (whichever occurs first)

Treatment

Salvage Radiation Therapy (SRT) RADIATION

SRT according to standard of care (SRT with at least 66 Gy)

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.)
• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Prof. Dr. med. Christian Gratzke: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Clinic of Urology, Medical Center - University of Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

RECRUITING

MeSH Terms

Conditions

Urologic Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases

Study Officials

• Christian Gratzke, Prof. Dr.

  University Medical Center - University of Freiburg, Clinical of Urology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Markus T Grabbert, Dr.

CONTACT

+49 761 270 28930; markus.grabbert@uniklinik-freiburg.de

Anika Josef, Dr.

CONTACT

+49 761 270 77110; anika.josef@uniklinik-freiburg.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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).

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: June 18, 2021
• Study Start: October 20, 2022
• Primary Completion: July 1, 2025
• Study Completion: April 1, 2026
• Last Updated: March 1, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)