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

Phase 2

• Conditions: Prostate Cancer
• Interventions: Drug: Pembrolizumab; Drug: Enzalutamide

• Registration Number: NCT03753243
• Lead Sponsor: Mark Garzotto, MD

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.

Study Timeline

• Study First Submitted: 2018-11-20
• Study First Submitted QC: 2018-11-21
• Study First Posted: 2018-11-26
• Study Start: 2018-12-03
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-19
• Last Update Posted: 2022-04-20
• Primary Completion: 2022-09-03
• Study Completion: 2023-04-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 32

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention	Pembrolizumab	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.
Intervention	Enzalutamide	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.

Primary Outcome Measures

Name	Time	Method
Pathologic Complete Response	4 months	No cancer detected on pathology examination of prostatectomy specimen

Secondary Outcome Measures

Name	Time	Method
Treatment Related Adverse Events	4 months + 30 days	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	4 months + 30 days	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	4 months	Prostate-Specific Antigen (PSA) \< 0.1 ng/mL prior to prostatectomy
Incidence of Surgical Complications	4 months	Clavien-Dindo Classification of Surgical Complications compared to historical department incidence rates.

Trial Locations

Locations (1)

VA Portland Healthcare System; 🇺🇸 Portland, Oregon, United States