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

NCT ID: NCT03753243

Last Updated: 2022-04-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-03
• Study Completion Date: 2023-04-30

Brief Summary

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.

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.

Enzalutamide

Intervention Type: DRUG

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.

Interventions

Pembrolizumab

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Keytruda; Xtandi

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Astellas Pharma Inc

INDUSTRY

Sponsor Role: collaborator

Mark Garzotto, MD

FED

Sponsor Role: lead

Responsible Party

Mark Garzotto, MD

Director of Urologic Oncology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mark Garzotto, MD

Role: PRINCIPAL_INVESTIGATOR

Portland VA Medical Center

Locations

VA Portland Healthcare System

Portland, Oregon, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Wesley Stoller, MA

Role: CONTACT

stoller@ohsu.edu

5032208262 ext. 54931

Mark Garzotto, MD

Role: CONTACT

mark.garzotto@va.gov

5032208262 ext. 51982

Facility Contacts

Wesley Stoller, MA

Role: primary

stoller@ohsu.edu

503-220-8262 ext. 54931

References

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.

Reference Type: DERIVED

PMID: 35537411 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

15235

Identifier Type: -

Identifier Source: org_study_id