A Randomized, Double-blind, Phase 3 Efficacy Trial of PROSTVAC-V/F +/- GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine whether PROSTVAC alone or in combination with GM-CSF is effective in prolonging overall survival in men with few or no symptoms from metastatic, castrate-resistant prostate cancer.

Detailed Description
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BNIT-PRV-301 is a randomized, placebo-controlled, multi-center, global Phase 3 efficacy trial of PROSTVAC in men with asymptomatic or minimally symptomatic, metastatic, castrate-resistant prostate cancer. It is a 3-arm study and will evaluate overall survival in two separate comparisons, PROSTVAC plus adjuvant dose GM-CSF versus controls, and PROSTVAC without GM-CSF versus controls. Patients will be randomized with equal probability into one of three double-blind arms. The intended interventions for randomized patients are: (Arm V+G) PROSTVAC-V/F plus adjuvant dose GM-CSF (Arm V) PROSTVAC-V/F plus GM-CSF placebo (Arm P) Double placebo

Official Title
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A Randomized, Double-blind, Phase 3 Efficacy Trial of PROSTVAC-V/F +/- GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer

Conditions
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Prostate Cancer Metastatic

Intervention / Treatment
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* Biological: PROSTVAC-V
* Biological: PROSTVAC-F
* Drug: GM-CSF
* Other: GM-CSF Placebo
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men, ≥18years of age with documented asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. Documented progressive disease post surgical castration or during androgen suppression therapy, or during complete androgen blockade therapy and withdrawal. Documented by either criterion a (Radiological progression), OR criterion b (PSA progression). Radiological progression defined as any new/enlarging bone metastases or new/enlarging lymph node disease, consistent with prostate cancer. OR PSA progression defined by sequence of rising values separated by > 1 week (2 separate increasing values) over a threshold minimum of 2.0 ng/ml. (PCWG2 PSA eligibility criteria). Chemotherapy naïve and Vaccinia-experienced (previous smallpox vaccination). Currently using a GnRH agonist or antagonist (unless surgically castrated). Exclusion Criteria: Cancer-related pain requiring scheduled opioid narcotics for control (as needed, ≤ 2x per week is allowed). Metastasis to organ systems other than lymph nodes and/or bone. Estimated PSA doubling time of <1 month as established within 6 months of the anticipated first dose of vaccine or placebo. Concurrent or prior Provenge (sipuleucel-T) immunotherapy for prostate cancer. Receipt of an investigational agent within 30 days (or 60 days for an antibody-based therapy) of the first planned dose of PROSTVAC-V/F. History of prior malignancies other than prostate cancer within the past 3 years, excluding successfully resected basal or squamous cell carcinoma of the skin. Congestive heart failure (NYHA Class II, III, or IV), unstable angina, ventricular or hemodynamically significant atrial arrhythmia, or cardiovascular disease such as stroke or myocardial infarction (current or within the past 6 months) Confirmed positive for HIV, hepatitis B, and /or hepatitis C. Immunodeficiency or splenectomy. History of or active autoimmune disease, persons with vitiligo are not excluded. Diabetics are not excluded if the condition is well controlled. History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PROSTVAC-V/F-TRICOM + GM-CSF<br>PROSTVAC-V-TRICOM PROSTVAC-F-TRICOM GM-CSF | Biological: PROSTVAC-V<br> <br> Biological: PROSTVAC-F<br> <br> Drug: GM-CSF<br> <br> |
| Experimental: PROSTVAC-V/F-TRICOM + GM-CSF placebo<br>PROSTVAC-V-TRICOM PROSTVAC-F-TRICOM GM-CSF placebo | Biological: PROSTVAC-V<br> <br> Biological: PROSTVAC-F<br> <br> Other: GM-CSF Placebo<br> <br> |
| Placebo Comparator: Placebo Control<br>PROSTVAC V/F Placebo + GM-CSF Placebo | Other: GM-CSF Placebo<br> <br> Biological: Placebo<br>* PROSTVAC V/F Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The time between the date of randomization and the date of death due to any cause. Subjects who did not experience death or the competing events of definite loss to follow-up or withdrawal of consent were right censored at the date of last contact. OS was calculated using the formula: OS = Date of death/competing event/censoring - date of randomization + 1. | Randomization through the date of death due to any cause. Subjects were followed up for approximately 6 years from the first subject randomized to the completion of the study. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Alive Without Event at 6 Months | A binary assessment that was performed for the 6-months timepoint for the categories of radiographic progression, pain progression, initiation of chemotherapy or death. Subjects without an event prior to 6-months were evaluated at 6-months. Subjects without event by 6-months and were not evaluated at 6-months were assumed to have had an event and analyzed as such. Progression events were defined as: (1) Two new lesions on bone scan, new metastases on CT scans, or an increased size of nodal lesions per RECIST 1.1. Bone or CT scans occurring prior to calendar month 6 were used to determine radiographic progression. (2) Introduction of scheduled opioid narcotics for cancer-related pain control. (3) Initiation of chemotherapy for prostate cancer was assessed as collected on progression forms as well as in cancer treatment and concomitant medications logs. (4) Death. | Randomization through Week 25/End of Treatment visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PROSTVAC, metastatic, prostate cancer, castrate-resistant, vaccine, immunotherapy, Phase 3