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

NCT02312557 | Active Not Recruiting Phase 2 Results DMC

• 5 other identifiers: IRB00011025NCI-2014-02131CR00025312MR00044410CRQ 2015
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Castration-Resistant Prostate Carcinoma; Hormone-Resistant Prostate Cancer; PSA Progression; Recurrent Prostate Carcinoma; Stage IV Prostate Adenocarcinoma Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• PSA Response, Defined by a PSA Decrease of at Least 50% Confirmed by a Second Measurement at Least 3 Weeks Later

  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.

  Up to 30 days after completion of study treatment, up to approximately 2.5 years total.

Secondary Outcomes (12)

• Changes in T Cell Activation as Measured in Whole Blood

  Baseline to up to 4 weeks

• Changes in T Cell Numbers as Measured in Whole Blood

  Baseline to up to 4 weeks

• Changes in T Cell Phenotype as Measured in Whole Blood

  Baseline to up to 4 weeks

• Circulating Tumor Cells

  Up to 4 weeks

• Deoxyribonucleic Acid Mutation

  Up to 2.5 years

Study Arms (1)

Treatment (pembrolizumab)

EXPERIMENTAL

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.

Drug: Enzalutamide; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Enzalutamide DRUG

Given PO

Also known as: ASP9785, MDV3100, Xtandi

Treatment (pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ENTRY CRITERIA: Metastatic, castration resistant prostate cancer progressing on enzalutamide after initial response to enzalutamide
• Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma; patients without histologically confirmed adenocarcinoma may be eligible if both the treating physician and the study principal investigator (PI) agree that the patient?s history is unambiguously indicative of advanced adenocarcinoma
• Be willing and able to provide written informed consent/assent for the trial
• Be \>= 18 years of age on day of signing informed consent
• Have metastatic disease
• Have permission to access tissue from an archival tissue sample; (absence of archival tissue will not preclude trial participation)
• Has a metastatic deposit that can be biopsied
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) \>= 1,500/mcL, performed within 28 days of treatment initiation
• Platelets \>= 100,000/mcL, performed within 28 days of treatment initiation
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L, performed within 28 days of treatment initiation
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]); creatinine clearance should be calculated per institutional standard, performed within 28 days of treatment initiation
• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN, performed within 28 days of treatment initiation
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases, performed within 28 days of treatment initiation
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (only if submitting to a biopsy), performed within 28 days of treatment initiation

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment; the use of physiologic doses of corticosteroids may be approved after consultation with the sponsor
• Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier; denosumab is a prohibited medication on study and for 4 weeks prior to day 1
• Has had chemotherapy for castration-resistant disease; chemotherapy for castration-sensitive disease is permitted
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ bladder cancer that has undergone potentially curative therapy
• Has known brain metastases and/or carcinomatous meningitis
• Has a history of seizure
• Has allergy to enzalutamide
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; a severe autoimmune disease is one that requires a significant medical intervention such as hospitalization; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren?s syndrome will not be excluded from the study
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject?s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• Collins Medical Trust: collaborator
• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• Graff JN, Beer TM, Alumkal JJ, Slottke RE, Redmond WL, Thomas GV, Thompson RF, Wood MA, Koguchi Y, Chen Y, Latour E, Bergan RC, Drake CG, Moran AE. A phase II single-arm study of pembrolizumab with enzalutamide in men with metastatic castration-resistant prostate cancer progressing on enzalutamide alone. J Immunother Cancer. 2020 Jul;8(2):e000642. doi: 10.1136/jitc-2020-000642.

  PMID: 32616555 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; pembrolizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Rachel Slottke
• Organization: Oregon Health & Science University

slottker@ohsu.edu

503-494-6117

Study Officials

• Julie Graff, M.D.

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 4, 2014
• First Posted: December 9, 2014
• Study Start: November 18, 2014
• Primary Completion: August 22, 2024
• Study Completion (Estimated): June 30, 2026
• Last Updated: December 3, 2025
• Results First Posted: January 20, 2025

Record last verified: 2025-11

Locations

US (1)