Neoadjuvant Pembrolizumab Plus Androgen Axis Blockade Prior to Prostatectomy for High Risk Localized Prostate Cancer

Phase II Study of Neoadjuvant Pembrolizumab Plus Intensive Androgen Axis Blockade Prior to Prostatectomy for High Risk Localized Prostate Cancer

Pembrolizumab will be administered at a dose of 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Enzalutamide will be administered at dose of 160 mg orally every day. All patients will be required to have at least one high-risk criteria.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Enzalutamide

Detailed Description

The investigators propose to study the effects of pembrolizumab combined with intensive androgen receptor (AR) targeting prior to prostatectomy with extended pelvic lymph node dissection in subjects with high-risk localized prostate cancer (HRLPC).

Trial Design- single arm, single-stage, open label Phase II of neoadjuvant immune-hormonal therapy in high-risk localized prostate cancer.

Objectives To evaluate efficacy and safety of pembrolizumab combined with intensive AR targeting prior to prostatectomy in subjects with high-risk localized prostate cancer (HRLPC).

Primary Endpoint Pathologic complete response (pCR) defined as absence of detectable malignant cells in the prostatectomy specimen evaluated by standard histologic techniques.

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wesley Stoller, MA; Phone Number: 54931 5032208262; Email: stoller@ohsu.edu
• Study Contact Backup: Name: Mark Garzotto, MD; Phone Number: 51982 5032208262; Email: mark.garzotto@va.gov

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • VA Portland Healthcare System
      • Contact: Wesley Stoller, MA; Phone Number: 54931 503-220-8262; Email: stoller@ohsu.edu
      • Principal Investigator: Mark Garzotto, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Be willing and able to provide written informed consent/assent for the trial.
• Capability to understand and comply with the protocol and signed informed consent document.
• Be ≥ 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• Histologically confirmed, non-metastatic adenocarcinoma of the prostate
• Prostatectomy with extended lymph node dissection planned as primary therapy
• 10 year or longer life expectancy based on other co-morbidities
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

• Any one of the following three high risk features:

  • Gleason grade > 8-10
  • PSA > 20 ng/ml
  • Clinical stage T3a (resectable)
• No evidence of metastases .
• No other diagnosis of malignancy (with exception of non-melanoma skin cancer or a malignancy diagnosed ≥5 years ago).
• Male subjects of childbearing potential must agree to use an adequate method of contraception. Contraception, starting with the first dose of study therapy through the time of surgery. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Demonstrate adequate organ function, all screening labs should be performed within 30 days of treatment initiation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Intervention; Treatment will be planned for a total of 14 to 16 weeks. Pembrolizumab will be administered every 3 weeks via IV infusion with a dose of 200 mg per infusion. Enzalutamide will be given orally and dispensed to the patient on the date of their first infusion. The dosage of Enzalutamide will be 160 mg, administered once daily for approx. 16 weeks. GNRH agonist therapy will be administered as a standard of care therapy and will follow a standard dosage to maintain castrate levels.

Drug: Pembrolizumab; Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.; Other Names: Keytruda; Drug: Enzalutamide; Patients will receive daily oral doses of study drug (enzalutamide 160 mg/day), which will be administered as four capsules/day to be taken at or near the same time each day.; Other Names: Xtandi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response	No cancer detected on pathology examination of prostatectomy specimen	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Related Adverse Events	Grade 3 or higher adverse event (AE) possibly related or related to any of three treatment drugs (pembrolizumab, enzalutamide, Gonadotropin-releasing hormone (GNRH) agonist) per CTCAE v4.03, evaluated up until 30 days after prostatectomy	4 months + 30 days
Immune -related Adverse Events	Grade 2 or higher immune related AE possibly related or related to any of three treatment drugs (pembrolizumab, enzalutamide, GNRH agonist) per CTCAE v4.03, evaluated up until 30 days after prostatectomy	4 months + 30 days
Biochemical Complete Response	Prostate-Specific Antigen (PSA) < 0.1 ng/mL prior to prostatectomy	4 months
Incidence of Surgical Complications	Clavien-Dindo Classification of Surgical Complications compared to historical department incidence rates.	4 months

Collaborators and Investigators

• Sponsor: Mark Garzotto, MD
• Collaborators: Merck Sharp & Dohme LLC; Astellas Pharma Inc
• Investigators: Principal Investigator: Mark Garzotto, MD, Portland VA Medical Center

Publications and helpful links

General Publications

• Pala L, De Pas T, Conforti F. Boosting anticancer immunotherapy through androgen receptor blockade. Cancer Cell. 2022 May 9;40(5):455-457. doi: 10.1016/j.ccell.2022.04.007. Epub 2022 May 9.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 3, 2018
• Primary Completion (ANTICIPATED): September 3, 2022
• Study Completion (ANTICIPATED): April 30, 2023

Study Registration Dates

• First Submitted: November 20, 2018
• First Submitted That Met QC Criteria: November 21, 2018
• First Posted (ACTUAL): November 26, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 20, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Neoadjuvant; Programmed cell death protein 1 (PD-1)
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: 15235

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
• product manufactured in and exported from the U.S.: No