Enzalutamide With or Without Vaccine Therapy for Advanced Prostate Cancer

Phase 2

Completed

Conditions: Prostate Cancer

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

Registration Number: NCT01867333

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Background:

- 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.

Objectives:

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

Eligibility:

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

Design:

* 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.

Detailed Description: Background:

* 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 (rilimogene galvacirepvec/rilimogene glafolivec) therapy was associated with a prolongation of survival by 8.5 months in men with metastatic castrate-resistant 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.

Objective:

-Determine if prostate-specific antigen (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.

Design:

* 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.

Eligibility:

* 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 57

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 2 - Enzalutamide with Prostate-Specific Antigen (PSA)-TRICOM	PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -F/TRICOM	Enzalutamide with PSA-TRICOM. Enzalutamide will be given at the standard dose of 160 mg daily with vaccine given week 1 (vaccinia-PSA-TRICOM, 2x10(8) infectious units subcutaneously) and then week 3, 5 and then monthly fowlpox-vaccine (1x10(9) infectious units subcutaneously).
Arm 2 - Enzalutamide with Prostate-Specific Antigen (PSA)-TRICOM	PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM	Enzalutamide with PSA-TRICOM. Enzalutamide will be given at the standard dose of 160 mg daily with vaccine given week 1 (vaccinia-PSA-TRICOM, 2x10(8) infectious units subcutaneously) and then week 3, 5 and then monthly fowlpox-vaccine (1x10(9) infectious units subcutaneously).
Arm 1 - Enzalutamide alone	Enzalutamide	Enzalutamide alone. Enzalutamide will be given at the standard dose of 160 mg daily.
Arm 2 - Enzalutamide with Prostate-Specific Antigen (PSA)-TRICOM	Enzalutamide	Enzalutamide with PSA-TRICOM. Enzalutamide will be given at the standard dose of 160 mg daily with vaccine given week 1 (vaccinia-PSA-TRICOM, 2x10(8) infectious units subcutaneously) and then week 3, 5 and then monthly fowlpox-vaccine (1x10(9) infectious units subcutaneously).

Primary Outcome Measures

Name	Time	Method
Time to Progression (TTP)	Median follow-up of 55.4 months	Time to progression is defined as the duration of time from start of treatment to time of disease progression. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions can also be considered progression if they meet the size criteria for target lesions.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Median potential follow-up of 68.5 months	Overall survival is defined as the date of on-study to the date of death from any cause or last follow up.
Time to Prostate-specific Antigen (PSA) Progression	Median follow-up of 55.4 months	PSA progression is defined by a sequence of rising values separated by \>1 week (2 separate increasing values over a minimum of 2ng/ml or 25% higher (Prostate Cancer Clinical Trials Working Group (PCWG2) PSA eligibility criteria).