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Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01875250
Recruitment Status : Completed
First Posted : June 11, 2013
Results First Posted : September 16, 2020
Last Update Posted : September 16, 2020
Information provided by (Responsible Party):
Ravi A. Madan, M.D., National Cancer Institute (NCI)

Brief Summary:


- Enzalutamide is a well tolerated hormone therapy that is used to treat advanced prostate cancer. It is given to help kill cancer cells and limit cancer cell growth. A new possible way of treating prostate cancer is using a therapeutic cancer vaccine (immune stimulating therapy) that may help activate the immune system against the cancer. The immune stimulating vaccine will help white blood cells recognize and kill the cancer cells throughout the body. This vaccine therapy has been tested in hundreds of patients and is very well tolerated. 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.

Key Eligibility:

  • Men at least 18 years of age who have advanced castration sensitive prostate cancer.
  • Patients must have testosterone within the normal range
  • No evidence of metastatic prostate cancer on computed tomography (CT) or Bone scan
  • No history of autoimmune diseases
  • No previous immunotherapy within 3 years


  • 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 for 3 months. This form of intermittent therapy is common in this population of patients.
  • The vaccine group of participants will receive 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 injection during the third week of treatment, and one in the fifth week. The vaccine will then be given every 4 weeks until 21 weeks have passed.
  • Treatment will be monitored with frequent blood tests and imaging studies.

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer
Actual Study Start Date : July 22, 2013
Actual Primary Completion Date : September 1, 2019
Actual Study Completion Date : February 28, 2020

Arm Intervention/treatment
Experimental: Arm A - Enzalutamide for 3 months
Enzalutamide for 3 months
Drug: Enzalutamide (Xtandi)
An androgen receptor inhibitor.
Other Name: Xtandi

Experimental: Arm B - Enzalutamide for 3 months + PSA-TRICOM
Enzalutamide 3 months + PSA-TRICOM (Prostvac-V/F) on weeks 1, 3, 5, 9,13,17 and 21
Biological: PROSTVAC-F (Fowlpox)/TRICOM
A recombinant fowlpox virus vector vaccine containing the genes for human prostate specific antigen (PSA) and three co-stimulatory molecules.

Biological: PROSTVAC-V (Vaccinia)/TRICOM
A recombinant vaccinia virus vector vaccine containing the genes for human prostate specific antigen (PSA) and three co-stimulatory molecules.

Drug: Enzalutamide (Xtandi)
An androgen receptor inhibitor.
Other Name: Xtandi

Primary Outcome Measures :
  1. Tumor Growth Rate [ Time Frame: 7 months ]
    Growth rate was measured using the growth rate equation -f(t) = exp (-d*t) + exp (g*t) -1 where exp is the base of the natural algorithm, e = 2.7182 and t is days since treatment started. The tumor growth rate equation measures Prostate Specific Antigen (PSA) rise over time. The UOM is unitless because this is a way to measure PSA kinetics.

Secondary Outcome Measures :
  1. Mean Pretreatment Plasma Vascular Endothelial Growth Factor (VEGF) Concentration 30 Days After the Start of Course 1 and Course 2 of Enzalutamide [ Time Frame: 30 Days After the Start of Course 1 and Course 2 of Enzalutamide ]
    VEGF was measured by the enzyme-linked immunosorbent assay (ELISA) assay. The lower limit of quantitation of assay was 9.0 pg/ml.

  2. Median Testosterone After 84 Days of Enzalutamide [ Time Frame: 84 days ]
    Normal testosterone is 270-1070 nd/dL.

  3. Percent Change in Prostate Specific Antigen (PSA) After 84 Days of Enzalutamide in Course 1 [ Time Frame: 84 days ]
    Median PSA change would be considered optimal.

  4. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) [ Time Frame: Date treatment consent signed to date off study, approximately 43 months and 13 days for Arm A, and 78 months and 6 days for Arm B. ]
    Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

  5. Median Time Until Prostate Specific Antigen (PSA) Recovery From Baseline Following Course 1 and Course 2 of Enzalutamide [ Time Frame: up to 41 months ]
    PSA recovery is defined as the return above baseline PSA in participants with normal testosterone and non-metastatic, castration sensitive prostate cancer.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

A. Histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, or Walter Reed National Military Medical Center prior to enrollment. If no pathologic specimen is available, patients may enroll with a pathologists report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.

B. Biochemical progression defined as follows:

  • For patients following definitive radiation therapy: a rise in prostate-specific antigen (PSA) of greater than or equal to 2 ng/mL above the nadir (per Radiation Therapy Oncology Group (RTOG)-American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria).
  • For patients following radical prostatectomy: rising PSA after surgical procedure. (Patients must have a PSA greater than or equal to 2ng/ml)

C. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky greater than or equal to 80%).

D. Patients must have a PSA doubling time of 12 months or less.

E. Patients must have a rising PSA as confirmed by 3 values done at least 1 week apart and over no less than 1 month.

F. Recovery from acute toxicity related to prior therapy, including surgery and radiation, or no toxicity greater than or equal to grade 2.

G. Negative computed tomography (CT) scan/magnetic resonance imaging (MRI) and bone scan for metastatic prostate cancer.

H. Hematological eligibility parameters (within 16 days before starting therapy):

Granulocyte count greater than or equal to 1000/mm(3)

Platelet count greater than or equal to 100,000/mm(3)

Hemoglobin (Hgb) greater than or equal to 10 g/dL

I. Biochemical eligibility parameters (within 16 days before starting therapy):

Hepatic function: bilirubin less than or equal to 1.5 mg/dL (OR in patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0), aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 2.5 times upper limit of normal.

J. No other active malignancies within the past 36 months (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder) or life-threatening illnesses

K. Willing to travel to the National Institutes of Health (NIH) for follow-up visits.

L. 18 years of age or older.

M. Able to understand and sign informed consent.

N. Baseline testosterone greater than or equal to lower limit of normal.

O. PSA less than or equal to 20 ng/mL.

P. The effects of enzalutamide, PSA-TRICOM or the combination 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. 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.


A. Immunocompromised status due to:

  • Human immunodeficiency virus (HIV) positivity.
  • Active autoimmune diseases such as Addison's disease, Hashimoto s thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Graves disease. Patients with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed.
  • Other immunodeficiency diseases

B. Chronic administration (defined as daily or every other day for continued use greater than 14 days) of corticosteroids deemed systemic by investigator within 28 days before the first planned dose of PSA-TRICOM. Use of inhaled steroids, nasal sprays, and topical creams for small body areas is allowed.

C. Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with patient's ability to carry out the treatment program.

D. History of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack, or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization).

E. Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (eg phytoestrogens and saw palmetto)

F. History of prior chemotherapy

G. History of prior immunotherapy within the last 3 years

H. Major surgery within 4 weeks prior to enrollment (Day 1 visit).

I. History of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide or poxviral vaccines (e.g., vaccinia vaccine)

J. Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin).

K. History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis

L. Previous serious adverse reactions to smallpox vaccination

M. Unable to avoid close contact or household contact with the following highrisk individuals for three weeks after the Day 1 vaccination: (a) children 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczematoid skin disorders, or (d) immunocompromised individuals, such as those with human immunodeficiency virus (HIV).

N. Receipt of an investigational agent within 30 days (or 60 days for an antibody based therapy) before the first planned dose of study drugs.

O. Patients who test positive for Hepatitis B virus (HBV) or hepatitis C virus (HCV)

P. Use of herbal products that may decrease PSA levels (e.g. saw palmetto)

Q. Any gastrointestinal disease that could hinder the absorption of enzalutamide

R. Uncontrolled hypertension (Systolic Blood Pressure (SBP)>170/ Diastolic Blood Pressure (DBP)>105)

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): NCT01875250

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
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)
  Study Documents (Full-Text)

Documents provided by Ravi A. Madan, M.D., National Cancer Institute (NCI):
Informed Consent Form  [PDF] December 22, 2017

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ravi A. Madan, M.D., Principal Investigator, National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01875250    
Other Study ID Numbers: 130153
First Posted: June 11, 2013    Key Record Dates
Results First Posted: September 16, 2020
Last Update Posted: September 16, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Ravi A. Madan, M.D., 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