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Castration-Resistant Prostate CarcinomaPhase 2NCT02312557

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

A Phase 2 study testing Enzalutamide, Laboratory Biomarker Analysis and Pembrolizumab in people with Castration-Resistant Prostate Carcinoma and Hormone-Resistant Prostate Cancer, run by OHSU Knight Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Enzalutamide, Laboratory Biomarker Analysis and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
1 siteUnited States
Study dates
18 Nov 2014to 7 May 2026
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (only if submitting to a biopsy), performed within 28 days of treatment initiation
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
  • Have a PSA or radiographic progression on enzalutamide; PSA progression is defined as two consecutive increases in PSA with the second level obtained at least 3 weeks after the first, and the second level of at least 0.5 ng/mL; soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria or >= 2 new lesions on bone scan
  • Have had either surgical castration OR be on luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy with serum testosterone < 50 ng/dl AND agree to stay on LHRH agonist or antagonist therapy during the study

Who cannot join

  • 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
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  • 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
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand (L)1, anti-PD-L2, anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways); previous treatment with sipuleucel-T is permitted
  • Has plans to receive cytotoxic chemotherapy, immune checkpoint inhibitors (eg CTLA-4 blockade), sipuleucel-T, radiopharmaceuticals, abiraterone or other experimental therapy during this study period
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment
  • Has rapid progression of visceral disease and, thus is a candidate for docetaxel; this determination will be at the discretion of the treating physician

Trial locations and contacts

1 site in 1 country.

United States1 site

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: Addition of Pembrolizumab Upon Progression on Enzalutamide in Men With mCRPC

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.

Read the detailed description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

  1. 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.

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

TERTIARY OBJECTIVES:

  1. 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.

Being tested
Enzalutamide, Laboratory Biomarker Analysis, Pembrolizumab
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EnzalutamideDrug

    Also called ASP9785, MDV3100, Xtandi

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT02312557
Study groupRoleWhat they receive
Treatment (pembrolizumab)ExperimentalINITIAL 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.
Receives: Drug: Enzalutamide; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (12)

  1. Changes in T Cell Activation as Measured in Whole Blood

    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.

    Measured: Baseline to up to 4 weeks

  2. Changes in T Cell Numbers as Measured in Whole Blood

    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.

    Measured: Baseline to up to 4 weeks

  3. Changes in T Cell Phenotype as Measured in Whole Blood

    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.

    Measured: Baseline to up to 4 weeks

  4. Circulating Tumor Cells

    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.

    Measured: Up to 4 weeks

  5. Deoxyribonucleic Acid Mutation

    Measured: Up to 2.5 years

  6. Immunohistochemistry for PD-1, PD-L1 and PD-L2 in Prostate Tissue

    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.

    Measured: Baseline

  7. Immunological Parameters, Including Leukocytes, Lymphocytes, and Macrophages in Prostate Tissue

    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.

    Measured: Baseline

  8. Objective Disease Response by Radiographs

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

    Measured: Up to 2.5 years

  9. Overall Survival

    Measured: Up to 2.5 years

  10. Percent Change in PSA

    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).

    Measured: Baseline to up to 30 days after completion of study treatment

  11. PSA Progression Free Survival, Where the Definition of Progression Will be PSA Progression Per Prostate Cancer Working Group 2 Criteria

    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).

    Measured: Up to 2.5 years

  12. Systemic Inflammatory Markers (Serum IL-8, IL-6, IL-1, TNF and TGF-beta)

    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.

    Measured: Up to 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2014 (estimated)
  2. Study start18 Nov 2014
  3. Primary completion22 Aug 2024
  4. Study completion7 May 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02312557
Sponsor's protocol ID
IRB00011025
Other IDs
NCI-2014-02131, CR00025312, MR00044410, CRQ 2015
Status last verified
Oct 2026
First submitted
4 Dec 2014
Last updated
28 Oct 2026
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 32616555

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Enzalutamide, Laboratory Biomarker Analysis and Pembrolizumab in people with Castration-Resistant Prostate Carcinoma and Hormone-Resistant Prostate Cancer, run by OHSU Knight Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PSA Response, Defined by a PSA Decrease of at Least 50% Confirmed by a Second Measurement at Least 3 Weeks Later (time frame: Up to 30 days after completion of study treatment, up to approximately 2.5 years total.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02312557, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.

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