Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Carcinoma

Adenocarcinoma

Prostatic Neoplasms

Disease Progression

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Disease Attributes

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

INITIAL TREATMENT PHASE: Patients who are progressing on enzalutamide will receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients continue to receive standard of care enzalutamide PO daily.

MONITORING PHASE: After completion of the initial treatment phase, patients continue to receive standard of care enzalutamide PO daily for the duration of the trial.

RETREATMENT PHASE: Patients with disease response or stability after the initial treatment phase will receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for an additional 4 courses in the absence of disease progression or unacceptable toxicity. Patients continue to receive standard of care enzalutamide PO daily for the duration of the trial.

Enzalutamide

Laboratory Biomarker Analysis

Julie Graff, M.D.

This phase II trial studies how well pembrolizumab works in treating patients with prostate cancer that has spread to other places in the body and keeps growing even when the amount of testosterone in the body is reduced to very low levels despite previous treatment with enzalutamide. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells.

PRIMARY OBJECTIVES:

I. Measure the anti-cancer activity of pembrolizumab in men with metastatic, castration resistant prostate cancer.

SECONDARY OBJECTIVES:

I. To investigate immunological and genetic parameters to evaluate for possible markers and functional changes that are predictive of a clinical response or linked to response or resistance to PD-1 inhibition.

II. To collect circulating tumor cells (CTCs) and determine the degree to which tumor characteristics are shared by the CTCs.

III. Changes in T cell numbers, activation, and phenotype as measured in whole blood at diagnosis and throughout therapy.

IV. Systemic inflammatory markers: serum interleukin (IL)-8, IL-6, IL-1, tumor necrosis factor (TNF) and transforming growth factor (TGF)-beta.

V. Objective disease response by radiographs. VI. Prostate-specific antigen (PSA) progression free survival. VII. Overall survival. VIII. Microbiome and correlation with response.

TERTIARY OBJECTIVES:

I. Additional genetic (deoxyribonucleic acid \[DNA\], ribonucleic acid \[RNA\]) and protein analyses will be conducted to further evaluate immunotherapy and profile/characterize disease.

OUTLINE:

INITIAL TREATMENT PHASE: Patients who are progressing on enzalutamide will receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients continue to receive standard of care enzalutamide orally (PO) daily.

MONITORING PHASE: After completion of the initial treatment phase, patients continue to receive standard of care enzalutamide PO daily for the duration of the trial.

RETREATMENT PHASE: Patients with disease response or stability after the initial treatment phase will receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for an additional 4 courses in the absence of disease progression or unacceptable toxicity. Patients continue to receive standard of care enzalutamide PO daily for the duration of the trial.

After completion of study treatment, patients are followed up at 30 days, and then every 12 weeks for 2.5 years.

Pembrolizumab in Treating Patients With Metastatic Castration Resistant Prostate Cancer Previously Treated With Enzalutamide

Addition of Pembrolizumab Upon Progression on Enzalutamide in Men With mCRPC

One-sample binomial test will be used to assess whether the proportion of PSA response (PSA decrease of at least 50%) is significantly greater than 0.05. Univariable logistic regression analysis will be conducted to assess the association between immunological parameters and PSA response responses. Scale in logit will be assessed for all continuous parameters that are identified to be significantly associated with PSA response. Descriptive statistical analysis will be conducted. The proportion estimate will be reported with 95% confidence interval.

Descriptive statistical analysis will be conducted. The proportion estimate will be reported with 95% confidence interval, and the continuous variables will be summarized using nmissing, mean, std, median, min, and max.

Descriptive statistical analysis will be conducted. The proportion estimate will be reported with 95% confidence interval.

Descriptive statistical analysis will be conducted. The proportion estimate will be reported with 95% confidence interval, and the continuous variables will be summarized using number (n)missing, mean, standard deviation (std), median, minimum (min), and maximum (max).

If there is a decline from baseline, progression is an increase in PSA that is 25% and 2 ng/ml above the nadir, which is confirmed by a second value 3 or more weeks later (i.e., a confirmed rising trend). Kaplan-Meier curve will be plotted to illustrate the PSA progression free survival for all, and for subgroups (abiraterone versus no prior abiraterone and sipuleucel-T versus no prior sipuleucel-T). Descriptive statistical analysis will be conducted. The proportion estimate will be reported with 95% confidence interval.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pembrolizumab in Treating Patients With Metastatic Castration Resistant Prostate Cancer Previously Treated With Enzalutamide	NCT02312557	Castration-Resi... Hormone-Resista... PSA Progression Recurrent Prost... Stage IV Prosta...	Enzalutamide Laboratory Biom... Pembrolizumab	18 Years -	OHSU Knight Cancer Institute
Pembrolizumab in Treating Patients With Metastatic Castration Resistant Prostate Cancer Previously Treated With Enzalutamide	NCT02312557	Castration-Resi... Hormone-Resista... PSA Progression Recurrent Prost... Stage IV Prosta...	Enzalutamide Laboratory Biom... Pembrolizumab	18 Years -	OHSU Knight Cancer Institute

Spots Global Cancer Trial Database for stage iv prostate adenocarcinoma cancer ajcc v8