Clinical Trials /

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

NCT04569461

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trimodality Approach to Localized Prostate Cancer: Pembrolizumab, ADT, and SBRT Followed by Prostatectomy
  • Official Title: Trimodality Approach to Unfavorable Localized Prostate Cancer: a Prospective Trial of Neoadjuvant Pembrolizumab, ADT, and Prostate SBRT Followed by Radical Prostatectomy

Clinical Trial IDs

  • ORG STUDY ID: Pro00103396
  • NCT ID: NCT04569461

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
pembrolizumabKEYTRUDASingle Arm
Short-term androgen deprivation therapySTADT, Short-term ADTSingle Arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Single ArmExperimentalSubjects 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.
  • pembrolizumab
  • Short-term androgen deprivation therapy

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of subjects who achieve biochemical progression-free survival (BPFS) at 24 months (2 years)
Time Frame:24 months
Safety Issue:
Description: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

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Bridget Koontz

Trial Keywords

  • prostate cancer
  • KEYTRUDA
  • pembrolizumab
  • androgen deprivation therapy
  • prostatectomy
  • localized prostate cancer
  • ADT
  • SBRT
  • stereotactic

Last Updated

September 29, 2020