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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03753243
• Other study ID #: 15235
• Status: Recruiting
• Phase: Phase 2
• Start date: December 3, 2018
• Est. completion date: April 30, 2023

Study information

• Verified date: April 2022
• Source: Portland VA Medical Center
• Contact: Wesley Stoller, MA
• Phone: 5032208262
• Email: stoller[@]ohsu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: April 30, 2023
• Est. primary completion date: September 3, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	VA Portland Healthcare System	Portland	Oregon

Sponsors (3)

Lead Sponsor	Collaborator
Mark Garzotto, MD	Astellas Pharma Inc, Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response	No cancer detected on pathology examination of prostatectomy specimen	4 months
Secondary	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
Secondary	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
Secondary	Biochemical Complete Response	Prostate-Specific Antigen (PSA) < 0.1 ng/mL prior to prostatectomy	4 months
Secondary	Incidence of Surgical Complications	Clavien-Dindo Classification of Surgical Complications compared to historical department incidence rates.	4 months