WITHDRAWN

Trimodality Approach of Low Dose iOnizing Radiation With or Without Neoadjuvant Pembrolizumab and Prostatectomy for Men With Intermediate/High Risk Prostate Cancer (TALON)

Conditions

Prostate Cancer KEYTRUDA pembrolizumab prostatectomy localized prostate cancer prostate radiation low dose prostate radiation

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study will enroll prostate cancer patients with an unfavorable intermediate- or high-risk diagnosis. The purpose of this study is to determine whether a regimen of pembrolizumab and low dose prostate radiation or low dose prostate radiation alone prior to a prostatectomy affects cells of the immune system and if it is a safe option for this stage of prostate cancer. Participants will be randomized 1:1 (like flipping a coin) to receive pembrolizumab, low dose prostate radiation and a prostatectomy or low dose prostate radiation and a prostatectomy. Pembrolizumab is an investigational drug that increases the ability of the immune system to kill tumor cells. Low dose radiation can alter the way tumor cells look to the immune cells. For example, the immune cells may express different proteins that make them more susceptible to immune cell killing or the structure of the tumor may be altered to allow the immune cells to infiltrate the tumor more thoroughly. The prostate tissue collected from the prostatectomy will be analyzed for differences in pathology and local immune cell infiltration, and participants will be followed for 2 years to watch for prostate specific antigen (PSA) recurrence and prostate cancer recurrence.

Official Title

Trimodality Approach of Low Dose iOnizing Radiation With or Without Neoadjuvant Pembrolizumab and Prostatectomy for Men With Intermediate/High Risk Prostate Cancer (TALON)

Quick Facts

Study Start:2025-06

Study Completion:2026-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:WITHDRAWN

Study ID

NCT04569461

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Ability to understand and the willingness to sign a written informed consent document. 2. Age ≥ 18 years 3. Histologic evidence of adenocarcinoma of the prostate who are deemed candidates for radical prostatectomy. Variants such as neuroendocrine components or ductal carcinoma are allowed. Pure small cell carcinoma is not allowed. 4. At least one unfavorable intermediate or high risk factors or classified as high risk clinically localized disease as defined by NCCN guidelines: 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix A) 6. Adequate normal organ and marrow function as defined below by the following criteria within 10 days prior to first dose of study treatment.: 1. Hemoglobin ≥ 9.0 g/dL 2. Absolute neutrophil count (ANC ≥1.5 x 10\^9/L) 3. Platelet count ≥100 x 10\^9/L 4. Serum bilirubin ≤ 1.5 x Institutional Upper Limit of Normal (ULN) 5. AST/SGOT and ALT/SGPT ≤ 2.5 x ULN 6. Measured creatinine clearance (CL) \>50 mL/min 8. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.	1. History of or known bone, brain, visceral, or soft tissue metastasis, including lymph nodes based on standard of care imaging with CT or pelvic MRI showing no LNs greater than 1.5cm and bone scan showing no evidence of bone metastasis. 2. Prior pelvic radiation or prostate cryotherapy or high-intensity focused ultrasound (HIFU) 3. Any prior treatment with PD-1 or PD-L1 checkpoint inhibitors or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137, PD-L2). 4. Has received an investigational agent (or used an investigational device) within 4 weeks prior to study intervention administration. 5. Prior therapy for prostate cancer 6. Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 7. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid). 8. Presence of a condition requiring chronic steroid use (equivalent to \>10 mg of prednisone daily) or other immunosuppressive drugs (i.e., for organ transplant). The following are exceptions to this criterion: 1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) 2. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 9. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 10. History of another primary malignancy except for: 1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of investigational product (IP) and of low potential risk for recurrence 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease 3. Adequately treated carcinoma in situ without evidence of disease 11. History of allogenic stem cell transplant 12. History of active primary immunodeficiency 13. Known history of human immunodeficiency virus 14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. 15. Has not adequately recovered from major surgery or has ongoing surgical complications. 16. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. 17. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 18. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. 19. Any condition which, in the opinion of the investigator, would preclude participation in this trial

Inclusion Criteria

Exclusion Criteria

1. Ability to understand and the willingness to sign a written informed consent document.
2. Age ≥ 18 years
3. Histologic evidence of adenocarcinoma of the prostate who are deemed candidates for radical prostatectomy. Variants such as neuroendocrine components or ductal carcinoma are allowed. Pure small cell carcinoma is not allowed.
4. At least one unfavorable intermediate or high risk factors or classified as high risk clinically localized disease as defined by NCCN guidelines:
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix A)
6. Adequate normal organ and marrow function as defined below by the following criteria within 10 days prior to first dose of study treatment.:
1. Hemoglobin ≥ 9.0 g/dL
2. Absolute neutrophil count (ANC ≥1.5 x 10\^9/L)
3. Platelet count ≥100 x 10\^9/L
4. Serum bilirubin ≤ 1.5 x Institutional Upper Limit of Normal (ULN)
5. AST/SGOT and ALT/SGPT ≤ 2.5 x ULN
6. Measured creatinine clearance (CL) \>50 mL/min
8. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

1. History of or known bone, brain, visceral, or soft tissue metastasis, including lymph nodes based on standard of care imaging with CT or pelvic MRI showing no LNs greater than 1.5cm and bone scan showing no evidence of bone metastasis.
2. Prior pelvic radiation or prostate cryotherapy or high-intensity focused ultrasound (HIFU)
3. Any prior treatment with PD-1 or PD-L1 checkpoint inhibitors or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137, PD-L2).
4. Has received an investigational agent (or used an investigational device) within 4 weeks prior to study intervention administration.
5. Prior therapy for prostate cancer
6. Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
7. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid).
8. Presence of a condition requiring chronic steroid use (equivalent to \>10 mg of prednisone daily) or other immunosuppressive drugs (i.e., for organ transplant). The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
2. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
9. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
10. History of another primary malignancy except for:
1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of investigational product (IP) and of low potential risk for recurrence
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
3. Adequately treated carcinoma in situ without evidence of disease
11. History of allogenic stem cell transplant
12. History of active primary immunodeficiency
13. Known history of human immunodeficiency virus
14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.
15. Has not adequately recovered from major surgery or has ongoing surgical complications.
16. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
17. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
18. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
19. Any condition which, in the opinion of the investigator, would preclude participation in this trial

Contacts and Locations

Principal Investigator

Daniel George, MD

PRINCIPAL_INVESTIGATOR

Duke University

Study Locations (Sites)

Duke University Medical Center

Durham, North Carolina, 27710

United States

Collaborators and Investigators

Sponsor: Duke University

Daniel George, MD, PRINCIPAL_INVESTIGATOR, Duke University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-06

Study Completion Date2026-12-01

Study Record Updates

Study Start Date2025-06

Study Completion Date2026-12-01

Terms related to this study

Keywords Provided by Researchers

prostate cancer
KEYTRUDA
pembrolizumab
prostatectomy
localized prostate cancer
prostate radiation
low dose prostate radiation

Additional Relevant MeSH Terms

Prostate Cancer