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Protocol Details

A Randomized Phase II Trial Combining Vaccine Therapy with PROSTVAC /TRICOM and Enzalutamide vs. Enzalutamide Alone in Men with Metastatic Castration Resistant Prostate Cancer

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male
Min Age: 18
Max Age: N/A

Referral Letter Required


Population Exclusion(s)



Gene Transfer;
Androgen Receptor Antagonist;
Immune Response

Recruitment Keyword(s)



Prostate Cancer

Investigational Drug(s)


Investigational Device(s)



Biological/Vaccine: PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -F/TRICOM
Biological/Vaccine: PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM
Biological/Vaccine: Enzalutamide

Supporting Site

National Cancer Institute


- 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.

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-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

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Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, Manson K, Panicali DL, Laus R, Schlom J, Dahut WL, Arlen PM, Gulley JL, Godfrey WR. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010 Mar 1;28(7):1099-105. doi: 10.1200/JCO.2009.25.0597. Epub 2010 Jan 25.

Madan RA, Arlen PM, Mohebtash M, Hodge JW, Gulley JL. Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer. Expert Opin Investig Drugs. 2009 Jul;18(7):1001-11. doi: 10.1517/13543780902997928.

Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Fl(SqrRoot)(Copyright)chon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS; AFFIRM Investigators. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012 Sep 27;367(13):1187-97. Epub 2012 Aug 15.

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Principal Investigator

Referral Contact

For more information:

Ravi A. Madan, M.D.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 13N240B
10 Center Drive
Bethesda, Maryland 20892
(301) 480-7168

Amy R. Hankin, P.A.-C
National Cancer Institute (NCI)
(240) 858-3149

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


Additional Linkshttp://www.clinicaltrials.gov

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