Immunological Response to Intravesical BCG Therapy of Superficial Bladder Cancer by Prior Administration of RUTI®

Study Overview
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Brief Summary
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The RUTIVAC-1 study is a Phase I Clinical Trial designed to evaluate the systemic and mucosal immunological response and provide safety information after the use of RUTI® administration to individuals with NMIBC. The study will enroll individuals treated with Transurethral resection of bladder tumor (TURBT), diagnosed to have high-risk Non-muscle invasive bladder cancer (NMIBC) and suitable candidates for BCG therapy and who meet all eligibility criteria. Forty individuals will be recruited and randomized 1:1 to receive two subcutaneous shots of 25 μg RUTI® or placebo. After vaccination, individuals will receive the standard induction course, of intravesical Bacillus Calmette-Guerin (BCG)therapy (weekly BCG for six weeks). 4 to 8 weeks after the last intravesical BCG administration (BCG6) a visit will be performed (Visit 1, end of the interventional phase). Once all participants have performed VISIT 1 immunological assays will be performed and data will be analyzed. At the end of the Interventional Phase the blind will be opened, except for the study physicians who will remain blind during all the follow-up. All the individuals will be followed up for three years since TURBT.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase I Trial to Evaluate the Immunomodulatory Effect of RUTI® in Individuals With High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) Treated With Intravesical Bacillus Calmette-Guerin (BCG)

Conditions
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High-Risk Non-Muscle-Invasive Bladder Cancer

Intervention / Treatment
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* Drug: RUTI®
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written ICF for participation in the study. Age ≥18 years. General health status according to WHO ≤ 2. Have primary histologically confirmed T1 and/or high grade tumors and/or CIS. All visible papillary tumors must be completely resected. Early postoperative (within 24 hours of TURBT) single dose chemotherapy is allowed. BCG therapy indication. Never treated with BCG immunotherapy Willing to comply with study visits and procedures as per protocol Use of reliable contraception (see section 8.6) from the screening visit to 30 days after the last RUTI® or placebo injection. Exclusion Criteria: Life expectancy <5 years. Have a severe concomitant disease that might limit compliance or completion of the protocol. Have any other malignancy that might impact 3-year survival or might be potentially confused with NMIBC. Have other neoplasms. Have congenital or acquired immune deficiencies or under immunomodulatory treatment. Be receiving cytotoxic drugs or systemic corticosteroids within 8 weeks of receiving the first administration of BCG. Have received radiation therapy for their bladder cancer within 4 months prior to study entry. Have active infections (including urinary tract infections) defined as viral, bacterial, or fungal infections requiring therapy, HIV-positive status, concurrent febrile illness, gross hematuria or other factor that could influence tolerability to intravesical BCG therapy. Have biopsy, TURBT, or traumatic catheterization within 14 days of start of intravesical BCG treatment. Have active tuberculosis at screening visit. Active pregnancy or breastfeeding. Soy allergy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RUTI® injection<br> | Drug: RUTI®<br>* Administration of RUTI®<br>|
| Placebo Comparator: Sodium Chloride 0.9% injection<br> | Drug: Placebo<br>* Administration of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the systemic Th1 immune response. | IFN-γ production assessed by intracellular staining after ex vivo stimulation of PBMCs with PPD | Baseline, Day 10, weeks 2, 7 and 16 | 
| Changes in the local immune response in peritumoral tissue (Th1/Th2 ratio) | Th1/Th2 ratio in cells in the peritumoral tissue | Baseline and week 16 visit | 
| Changes in the local immune response in urine | Urine levels of cytokines by multiplex analysis | Baseline, Day 10, weeks 2, 7 and 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence date | Recurrence date | Until 3 years since TURBT | 
| Disease worsening | Disease worsening: events that included diagnosis of T2 or greater | Until 3 years since TURBT | 
| Death |  | Until 3 years since TURBT | 
| Proportion of patients who develop a Grade 3 or 4 local reactions | From Baseline to BCG administration number 6 | through study completion an average of 1,5 year | 
| Proportion of patients who develop a Grade 3 or 4 systemic reactions | Proportion of patients who develop a Grade 3 or 4 systemic reactions (adverse events related to RUTI/placebo). | through study completion an average of 1,5 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NMIBC, Immunotherapy, RUTI, Non-muscle invasive bladder cancer