Prostate Cancer
Conditions
Keywords
Neoadjuvant, Programmed cell death protein 1 (PD-1)
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.
Interventions
DRUGPembrolizumab
Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
DRUGEnzalutamide
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.
Sponsors
Merck Sharp & Dohme LLC
Astellas Pharma Inc
Mark Garzotto, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
single arm, single-stage open label Phase II of neoadjuvant immune-hormonal therapy in high-risk Localized prostate cancer.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response | 4 months | No cancer detected on pathology examination of prostatectomy specimen |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
Primary ContactWesley Stoller, MA
Backup ContactMark Garzotto, MD
Outcome results
None listed