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

Primary Purpose

Prostate Cancer

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Pembrolizumab

Enzalutamide

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Neoadjuvant, Programmed cell death protein 1 (PD-1)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

VA Portland Healthcare SystemRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intervention

Arm Description

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.

Outcomes

Primary Outcome Measures

Pathologic Complete Response

No cancer detected on pathology examination of prostatectomy specimen

Secondary Outcome Measures

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

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

Biochemical Complete Response

Prostate-Specific Antigen (PSA) < 0.1 ng/mL prior to prostatectomy

Incidence of Surgical Complications

Clavien-Dindo Classification of Surgical Complications compared to historical department incidence rates.

Full Information

NCT ID

NCT03753243

First Posted

November 20, 2018

Last Updated

April 19, 2022

Sponsor

Mark Garzotto, MD

Collaborators

Merck Sharp & Dohme LLC, Astellas Pharma Inc

1. Study Identification

Unique Protocol Identification Number

NCT03753243

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

December 3, 2018 (Actual)

Primary Completion Date

September 3, 2022 (Anticipated)

Study Completion Date

April 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Mark Garzotto, MD

Collaborators

Merck Sharp & Dohme LLC, Astellas Pharma Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

Keywords

Neoadjuvant, Programmed cell death protein 1 (PD-1)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

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

Masking

None (Open Label)

Allocation

N/A

Enrollment

32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intervention

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Pembrolizumab

Other Intervention Name(s)

Keytruda

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Enzalutamide

Other Intervention Name(s)

Xtandi

Intervention Description

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.

Primary Outcome Measure Information:

Title

Pathologic Complete Response

Description

No cancer detected on pathology examination of prostatectomy specimen

Time Frame

4 months

Secondary Outcome Measure Information:

Title

Treatment Related Adverse Events

Description

Time Frame

4 months + 30 days

Title

Immune -related Adverse Events

Description

Time Frame

4 months + 30 days

Title

Biochemical Complete Response

Description

Prostate-Specific Antigen (PSA) < 0.1 ng/mL prior to prostatectomy

Time Frame

4 months

Title

Incidence of Surgical Complications

Description

Clavien-Dindo Classification of Surgical Complications compared to historical department incidence rates.

Time Frame

4 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Wesley Stoller, MA

Phone

5032208262

Ext

54931

stoller@ohsu.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Mark Garzotto, MD

Phone

5032208262

Ext

51982

mark.garzotto@va.gov

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark Garzotto, MD

Organizational Affiliation

Portland VA Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

VA Portland Healthcare System

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Wesley Stoller, MA

Phone

503-220-8262

Ext

54931

stoller@ohsu.edu

First Name & Middle Initial & Last Name & Degree

Mark Garzotto, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35537411

Citation

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.

Results Reference

derived

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

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