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Enzalutamide With or Without Vaccine Therapy for Advanced Prostate Cancer

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ClinicalTrials.gov Identifier: NCT01867333
Recruitment Status : Completed
First Posted : June 4, 2013
Last Update Posted : November 9, 2022
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


- Enzalutamide is a hormone therapy that is used to treat advanced prostate cancer. It is given after chemotherapy and surgery to help the body destroy the cancer cells. A new possible way of treating prostate cancer is using a vaccine that may help stimulate the immune system. It will help white blood cells recognize and kill the cancer cells in and around the prostate. Researchers want to see whether this vaccine, given with enzalutamide, is more effective at treating advanced prostate cancer than enzalutamide alone.


- To compare the safety and effectiveness of enzalutamide with and without vaccine therapy for advanced prostate cancer.


- Men at least 18 years of age who have advanced castration-resistant prostate cancer.


  • Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies will be used to monitor the cancer before treatment.
  • Participants will be separated into two groups. One group will have enzalutamide and the study vaccine. The other group will have enzalutamide alone.
  • All participants will take enzalutamide once a day. They will take the drug during 4-week cycles of treatment.
  • Treatment will be monitored with frequent blood tests and imaging studies. Participants will continue to take the study drug for as long as the cancer does not grow and the side effects are not severe.
  • The vaccine group of participants will also have the new study vaccine. They will have a single injection on the first day of the first study cycle. There will be regular booster injections afterward. There will be one on day 15 of the first cycle, the first day of the second cycle. The vaccine will then be given every 4 weeks for the next four cycles, and then every 12 weeks (every 3 cycles) thereafter. Participants will continue to have the study vaccine for as long as the cancer does not grow and the side effects are not severe.

Condition or disease Intervention/treatment Phase
Prostate Cancer Biological: PROSTVAC-F/TRICOM Biological: PROSTVAC-V/TRICOM Biological: Enzalutamide (Xtandi) Phase 2

Detailed Description:


  • Enzalutamide is a well-tolerated, modern androgen receptor antagonist (ARA) with more enhanced anti-tumor activity compared to previous ARAs. Phase III trial has demonstrated a 4.8 month improvement in survival and a 37% risk reduction in death in metastatic castration resistant prostate cancer (mCRPC) patients who have had previous docetaxel.
  • PROSTVAC is a therapeutic cancer vaccine which is designed to induce an anti-tumor immune response. In a randomized controlled Phase 2 trial, PROSTVAC therapy was associated with a prolongation of survival by 8.5 months in men with metastatic castrateresistant prostate cancer. An international Phase 3 trial is on-going.
  • Preclinical data has demonstrated that hormonal therapies such as ARAs can enhance the immune response through multiple mechanisms. Specifically, our group has shown that enzalutamide can increase thymic production of na(SqrRoot) ve T-cells, which could be activated by a cancer vaccine. Together, these data provide an important rationale to combine enzalutamide with PSA-TRICOM in mCRPC.
  • Data from the clinical trials with these therapies suggest that they are very well tolerated and without overlapping toxicity.


-Determine if PSA-TRICOM combined with enzalutamide will increase time to progression (as defined by Prostate Cancer Clinical Trials Working Group 2 criteria, incorporated in section 5.2) in chemotherapy-naive metastatic castration resistant prostate cancer patients compared to enzalutamide alone.


  • The study will randomize chemotherapy-naive, mCRPC patients to either enzalutamide alone or enzalutamide with PSA-TRICOM. Enzalutamide will be given at the standard dose of 160 mg daily.
  • PSA-TRICOM will be administered identical to the Phase III dosing with vaccine given week 1 (vaccinia-PSA-TRICOM, 2x10(8) units subcutaneously) and then week 3, 5 and then monthly fowlpox-vaccine (1x10(9) units subcutaneously).
  • After completing 6 months of vaccine, fowlpox-vaccine (1x10(9) units subcutaneously will be administered every 3 months. Patients will be treated until radiographic progression on scans using Prostate Cancer Working Group Criteria.


  • mCRPC patients with rising PSA or progressive disease despite castration levels of testosterone.
  • Chemotherapy-na(SqrRoot) ve with minimal or no symptoms related to prostate cancer.
  • Patients with history of autoimmune disease, brain/leptomeningeal metastasis, a second malignancy within 3 years of enrollment, or a severe co-morbid condition will be excluded.
  • Patients who have received abiraterone will be excluded
  • Patients will be stratified based on previous immunotherapy used as cancer treatment.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVAC /TRICOM and Enzalutamide vs. Enzalutamide Alone in Men With Metastatic Castration Resistant Prostate Cancer
Actual Study Start Date : August 12, 2013
Actual Primary Completion Date : September 28, 2022
Actual Study Completion Date : October 26, 2022

Arm Intervention/treatment
Experimental: 1
Enzaluatmide alone
Biological: Enzalutamide (Xtandi)
An androgen receptor inhibitor.

Experimental: 2
Enzaluatmide with PSA-TRICOM
A recombinant fowlpox virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules.

A recombinant vaccinia virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules.

Biological: Enzalutamide (Xtandi)
An androgen receptor inhibitor.

Primary Outcome Measures :
  1. Increase in time to progression [ Time Frame: 4-5 years ]
    Increase in time to disease progression

Secondary Outcome Measures :
  1. Increased overall survival [ Time Frame: 4-5 years ]
    increase in survival time

  2. Delay in PSA progression [ Time Frame: 4-5 years ]
    increase in time to PSA progression

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
  • Patients must have histologically or cytologically confirmed prostate cancer confirmed by either the Laboratory of Pathology at the NIH Clinical Center or Walter Reed National Military Medical Center at Bethesda prior to starting this study. If no pathologic specimen is available, patients may enroll with a pathologist s report showing a histological diagnosis of prostate cancer and a clinical course consistent with the disease.
  • Castrate testosterone level (<50ng/dl or 1.7nmol /L)
  • Metastatic disease documented by one of the following:
  • Metastatic bone disease on an imaging study, or
  • Soft tissue disease documented by CT/MRI, or
  • Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:

    i. Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR

ii. PSA progression defined by sequence of rising values separated by >1 week (2 separate increasing values over a minimum of 2ng/ml (PCWG2 PSA eligibility criteria) If patients had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal.

The requirement for a 4-6 week withdrawal period following discontinuation of flutamide, nilutamide or bicalutamide only applies to patients who have been on these drugs for at least the prior 6 months. For all other patients they must stop bicalutamide, nilutamide or flutamide the day prior to enrollment.

  • Asymptomatic or mildly symptomatic from prostate cancer; no use of regularly scheduled opiate analgesics for prostate cancer-related pain
  • Patients must agree to continue to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy
  • Age greater than or equal to 18 years.
  • ECOG performance status less than or equal to 1 (Karnofsky greater than or equal to 80%).
  • Patients must have normal organ and marrow function as defined below:
  • absolute neutrophil count greater than or equal to 1,500/mcL
  • platelets greater than or equal to 100,000/mcL
  • total bilirubin within normal institutional limits; for patients with Gilbert s syndrome, total bilirubin less than or equal to 3.0mg/dL
  • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal
  • creatinine within 1.5 X normal institutional limits, OR
  • creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal by Cockcroft-Gault Equation
  • The effects of enzalutamide alone or in combination with PSA-TRICOM on the developing human fetus are unknown. For this reason, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for three (3) months after the last dose of enzalutamide. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.
  • Ability of subject to understand and the willingness to sign a written informed consent document.


  • Patients who are immunocompromised as listed as follows:
  • Human immunodeficiency virus positivity due to the potential for decreased tolerance and may be at risk for severe side effects
  • Chronic administration (defined as daily or every other day for continued use >14 days) of systemic corticosteroids (including steroid eye drops) or other immune suppressive drugs, within 28 days before the first planned dose of PSA-TRICOM. Nasal, or inhaled steroid, and topical steroid creams for small body areas are not excluded.
  • Patients who have undergone allogeneic peripheral stem cell transplantation, or solid organ transplantation requiring immunosuppression
  • History of splenectomy
  • History of, or active autoimmune disease (such as Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia, systemic lupus erythematosis, Sjogrens syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome, Addisons disease, Hashimotos thyroiditis, Crohns or Graves disease). Patients with type 1 diabetes mellitus or vitiligo are not excluded if the condition is well controlled.
  • Patients with a history of brain/leptomeningeal metastasis
  • Patients who have been treated with abiraterone will be excluded
  • Patients with history of seizure as an adult including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Also, current or prior treatment with anti-epileptic medications for the treatment of seizures or history of loss of consciousness. Also transient ischemic attack within 12 months prior to randomization will not be permitted.
  • Patients with second malignancy within 3 years of enrollment; Patients curatively treated non-melanoma skin cancers or carcinoma in situ of the bladder, are not excluded.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide or poxviral vaccines (e.g., vaccinia vaccine)
  • Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin),
  • History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis
  • Previous adverse reactions to smallpox vaccination
  • Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the Day 1 vaccination: (a) children less than or equal to 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV.
  • Any condition which, in the opinion of the investigator, would prevent full participation in this trial (including the long-term follow-up), or would interfere with the evaluation of the trial endpoints.
  • Patients with prior chemotherapy for nonmetastatic prostate cancer within a year are excluded.
  • Receipt of an investigational agent within 28 days (or 56 days for an antibody-based therapy) before the first planned dose of study drugs. (Immune checkpoint inhibitors that are antibody-based will only require 28 days before enrollment)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension (SBP>170/ DBP>105) or psychiatric illness/social situations within 12 months that would limit compliance with study requirements.
  • Use of herbal products that may decrease PSA levels (e.g. saw palmetto)
  • Any gastrointestinal disease that could hinder the absorption of enzalutamide.
  • Patients who have had chemotherapy for metastatic castration-resistant prostate cancer. (Patients who have had docetaxel for metastatic castration sensitive disease per CHAARTED Data35 may enroll as long as they did not have progressive disease while on docetaxel and are 6 months removed from treatment, with all treatment related toxicities resolving to at least grade 1.)
  • Patients who have received radiation therapy, radionuclide therapy or undergone surgery within certain duration (4 weeks) of enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01867333

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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Ravi A Madan, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01867333    
Other Study ID Numbers: 130146
First Posted: June 4, 2013    Key Record Dates
Last Update Posted: November 9, 2022
Last Verified: November 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as the database is active.
Access Criteria: Clinical data will be made available via subscription to BTRIS and with permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Gene Transfer
Androgen Receptor Antagonist
Immune Response
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases
Anti-Infective Agents
Anti-Bacterial Agents
Antiprotozoal Agents
Antiparasitic Agents