Study of RV001V in Biochemical Failure Following Curatively Intended Therapy For Localized Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
This Phase II trial will enroll approximately 180 adult male patients with an earlier histologic diagnosis of prostatic adenocarcinoma and a biochemical recurrence (BCR) within 3 years of radical prostatectomy (RP) or definitive RT and no distant metastasis or locoregional recurrence. The trial is a randomized placebo-controlled double-blind study of a peptide cancer vaccine (RV001V).

Official Title
-----------------
A Phase 2, Double-Blind, Placebo Controlled Study of RV001V in Men With Biochemical Failure Following Curatively Intended Therapy For Localized Prostate Cancer (BRaVac)

Conditions
-----------------
Prostate Cancer Recurrent

Intervention / Treatment
-----------------
* Biological: RV001V
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: Biochemical recurrence (BCR) within 3 years of radical prostatectomy (RP) or definitive RT and no distant metastasis by standard CT imaging and bone scintigraphy, or locoregional recurrence (including lymph nodes) assessed by CT or multi-parametric magnetic resonance imaging (MRI) and confirmed with negative biopsy in case of prior RT. In case of BCR after RP all the following criteria should apply: a. PSA ≥0.2 ng/mL, b. PSA Doubling Time (PSADT) >3 months and <12 months In case of BCR after RT all the following criteria should apply: a. PSA >nadir + 2 ng/mL, b. PSADT >3 months and <12 months ECOG performance status ≤2. Laboratory values obtained ≤30 days prior to first vaccination: Hemoglobin ≥5.6 mmol/L; Absolute granulocyte count ≥1.5 x 109 /L, Platelets ≥100 x 109 /L., Total bilirubin ≤1.5 x upper limit of normal (ULN). Creatinine ≤1.5 x ULN. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤2.5 x ULN. Main Exclusion Criteria: Patients who are receiving androgen-deprivation therapy or considered a candidate for immediate anti-androgen deprivation therapy (ADT) as judged by the investigator. Patients who have received prior ADT are not eligible with the exception of those that received ADT ≤36 months in duration and ≥9 months before randomization and administered only in the neoadjuvant/adjuvant setting. Patient is planned for salvage therapy with RT or radical prostatectomy. Castrate level of serum testosterone <50 ng/dL at screening. PSA >10 ng/mL

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RV001V<br>Total of 12 SC vaccinations with RV001V. The first 6 vaccinations (priming period) will be given every 2 weeks, and then the following 5 vaccinations (7 through 11) will be administered with 4 weeks between each vaccination (Maintenance period), and the last vaccination (12th) will be administered 6 months following the 11th vaccination (boosting injection). | Biological: RV001V<br>* RV001V consists of the peptide RV001 and the adjuvant Montanide ISA 51. RV001 Vaccine 0.1 mg/mL (RV001V).<br>|
| Placebo Comparator: Placebo<br>Total of 12 SC vaccinations with placebo. The first 6 vaccinations (priming period) will be given every 2 weeks, and then the following 5 vaccinations (7 through 11) will be administered with 4 weeks between each vaccination (Maintenance period), and the last vaccination (12th) will be administered 6 months following the 11th vaccination (boosting injection). | Other: Placebo<br>* Placebo consist of the vaccine vehicle and the adjuvant Montanide ISA 51. Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to PSA progression | Time to PSA progression is defined as the time from randomization to doubling of PSA from the baseline value. The time to doubling will be estimated from a log-linear regression of PSA values. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety by frequency and severity of adverse events (AEs) | The numbers and proportions of patients with any treatment-emergent adverse event (TEAE), and any serious TEAE will be summarized | Up to 16 months | 
| Time to initiation of a subsequent antineoplastic therapy |  | Up to 3 years | 
| Proportion of patients showing a PSA response from baseline |  | Up to 3 years | 
| Disease-free survival (DFS) | time from randomization to documented clinical recurrence (distant or local), or death from any cause, censoring at date of last follow-up (FU) | Up to 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Biochemical relapse