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

This study will enroll prostate cancer patients with an unfavorable diagnosis. Subjects will receive a combination of pembrolizumab, Stereotactic Body Radiation Therapy (SBRT) to the prostate, and short-term androgen deprivation therapy (STADT or Short-term ADT). After receiving this "trimodal therapy", subjects will undergo a radical prostatectomy. The prostate tissue will be analyzed for differences in pathology and local immune cell infiltration, and subjects will be followed for 2 years to watch for prostate specific antigen (PSA) recurrence. The PSA results will be analyzed by comparing them to historical controls that have already been published, to learn if this therapy approach delays PSA rise.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: pembrolizumab; Radiation: Stereotactic body radiation therapy; Drug: Short-term androgen deprivation therapy; Procedure: Radical Prostatectomy

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Julia Hurrelbrink, RN, BSN; Phone Number: 919-681-1030; Email: julie.hurrelbrink@duke.edu
• Study Contact Backup: Name: Daniel George, MD

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
      • Principal Investigator: Bridget Koontz, MD
      • Contact: Julia Hurrelbrink, RN, BSN; Phone Number: 919-681-1030; Email: julia.hurrelbrink@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion 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 two intermediate risk factors or classified as high risk or very high risk clinically localized disease as defined by NCCN guidelines:

   a. Very high risk. At least one of the following: i. cT3b-T4 disease ii. Primary Gleason pattern of 5 iii. More than 4 cores with a Gleason sum of 8, 9 or 10 b. High risk: At least one of the following: i. cT3a disease ii. Gleason sum of 8, 9 or 10 iii. PSA ≥ 20 ng/ml c. At least two of the following intermediate risk factors: i. cT2b or cT2c disease ii. Gleason sum of 7 (either 3+4 or 4+3) iii. PSA 10-20 ng/ml

5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 (See Appendix A)
6. International Prostate Symptom Score (IPSS) of <18 within 28 days of Cycle 1 Day 1

7. 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 109/L)
   3. Platelet count ≥100 x 109/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.

Exclusion Criteria:

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 (eg, CTLA-4, OX 40, CD137, PD-L2).

4. Is currently participating in or has participated in a study of an investigational agent (or used an investigational device) within 4 weeks prior to the first dose of study treatment.

   a. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.

5. Prior therapy for prostate cancer

   a. Exceptions: Previous alpha-reductase inhibitor use allowed IF patient has not been taking for at least 30 days prior to study treatment initiation, OR if alpha reductase inhibitor was not used as a primary treatment of prostate cancer and the PSA on alpha-reductase inhibitor remains within eligibility when doubled. ]

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 (i.e. with use of disease modifying agents, corticosteroids beyond prednisone 10mg daily or equivalent, or other immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

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:

    c. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence d. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease e. 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 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.
16. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
17. Any condition which, in the opinion of the investigator, would preclude participation in this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single Arm; Subjects with unfavorable localized prostate cancer will be enrolled.This is a single arm, phase II study of pembrolizumab (Keytruda), SBRT, and Short-term Androgen Deprivation Therapy (STADT), known together as trimodality therapy, followed by radical prostatectomy 8 weeks after SBRT.

Drug: pembrolizumab; 200 mg of Pembrolizumab (KEYTRUDA) will be given by IV every 3 weeks for 5 cycles, a total of 15 weeks of treatment.; Other Names: KEYTRUDA; Radiation: Stereotactic body radiation therapy; SBRT will begin on week 7 of the study. The radiation will be given every other day in 5 fractions of 6 Gy for a total of 30 Gy of radiation exposure.; Other Names: SBRT; Drug: Short-term androgen deprivation therapy; Short-term ADT will last for five months. It will consist of treatment with a 1 month dose beginning on Day 0 of the study. Then it will continue with either a single 4 month dose on week 5, or 4 additional 1 month doses, depending on patient and physician preference.; Other Names: STADT; Short-term ADT; Procedure: Radical Prostatectomy; Radical prostatectomy surgery will be performed between week 17 and week 20 of the study, as scheduling permits.; Other Names: RP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects who achieve biochemical progression-free survival (BPFS) at 24 months (2 years)	BPFS will be defined as at least two PSAs 6+ weeks apart with first PSA > 0.2 ng/ml and second PSA >0.2 ng/ml occurring at least 3 months after surgery	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic response in prostatectomy tissue	Pathologic response will be graded using a published 3-point scale.	Through study completion, up to 1 year after last prostatectomy
12 week post-operative PSA	12 week post-operative PSA after pembrolizumab/SBRT/STADT/ RP,	12 weeks after prostatectomy

Collaborators and Investigators

• Sponsor: Daniel George, MD
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Daniel George, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (Actual): September 29, 2020

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: prostate cancer; SBRT; pembrolizumab; ADT; androgen deprivation therapy; prostatectomy; KEYTRUDA; localized prostate cancer; stereotactic
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Androgens
• Other Study ID Numbers: Pro00103396

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No