Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trimodality Approach to Localized Prostate Cancer: Pembrolizumab, ADT, and SBRT Followed by Prostatectomy (TALON)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04569461
Recruitment Status : Not yet recruiting
First Posted : September 29, 2020
Last Update Posted : September 30, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Bridget Koontz, Duke University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: pembrolizumab Radiation: Stereotactic body radiation therapy Drug: Short-term androgen deprivation therapy Procedure: Radical Prostatectomy Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Trimodality Approach to Unfavorable Localized Prostate Cancer: a Prospective Trial of Neoadjuvant Pembrolizumab, ADT, and Prostate SBRT Followed by Radical Prostatectomy
Estimated Study Start Date : November 1, 2020
Estimated Primary Completion Date : January 1, 2025
Estimated Study Completion Date : January 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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 Name: 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 Name: 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 Name: RP




Primary Outcome Measures :
  1. Percentage of subjects who achieve biochemical progression-free survival (BPFS) at 24 months (2 years) [ Time Frame: 24 months ]
    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


Secondary Outcome Measures :
  1. Pathologic response in prostatectomy tissue [ Time Frame: Through study completion, up to 1 year after last prostatectomy ]
    Pathologic response will be graded using a published 3-point scale.

  2. 12 week post-operative PSA [ Time Frame: 12 weeks after prostatectomy ]
    12 week post-operative PSA after pembrolizumab/SBRT/STADT/ RP,



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04569461


Contacts
Layout table for location contacts
Contact: Julia Hurrelbrink, RN, BSN 919-681-1030 julie.hurrelbrink@duke.edu
Contact: Bridget Koontz, MD

Locations
Layout table for location information
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Contact: Julia Hurrelbrink, RN, BSN    919-681-1030    julia.hurrelbrink@duke.edu   
Principal Investigator: Bridget Koontz, MD         
Sponsors and Collaborators
Bridget Koontz
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Principal Investigator: Bridget Koontz, MD Duke University
Layout table for additonal information
Responsible Party: Bridget Koontz, Associate Professor of Radiation Oncology, Duke University
ClinicalTrials.gov Identifier: NCT04569461    
Other Study ID Numbers: Pro00103396
First Posted: September 29, 2020    Key Record Dates
Last Update Posted: September 30, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bridget Koontz, Duke University:
prostate cancer
KEYTRUDA
pembrolizumab
androgen deprivation therapy
prostatectomy
localized prostate cancer
ADT
SBRT
stereotactic
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Pembrolizumab
Androgens
Antineoplastic Agents, Immunological
Antineoplastic Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs