Clinical trial NCT03753243: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Neoadjuvant
Programmed cell death protein 1 (PD-1)
Lead sponsor: Portland VA Medical Center
Sponsor class: FED
Collaborators: name: Merck Sharp & Dohme LLC
name: Astellas Pharma Inc
First posted: 2018-11-26
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: single arm, single-stage open label Phase II of neoadjuvant immune-hormonal therapy in high-risk Localized prostate cancer.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Pathologic Complete Response
timeFrame: 4 months
Secondary outcomes:
measure: Treatment Related Adverse Events
timeFrame: 4 months + 30 days
measure: Immune -related Adverse Events
timeFrame: 4 months + 30 days
measure: Biochemical Complete Response
timeFrame: 4 months
measure: Incidence of Surgical Complications
timeFrame: 4 months
Other outcomes:
Locations:
city: Portland
country: United States
facility: VA Portland Healthcare System
state: Oregon
Study officials:
affiliation: Portland VA Medical Center
name: Mark Garzotto, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.