Immunological Response to Intravesical BCG Therapy of Superficial Bladder Cancer by Prior Administration of RUTI® (RUTIVAC-1)

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)

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.

Study Overview

• Status: Completed
• Conditions: High-Risk Non-Muscle-Invasive Bladder Cancer
• Intervention / Treatment: Drug: RUTI®; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Germans Trias i Pujol Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written ICF for participation in the study.
2. Age ≥18 years.
3. General health status according to WHO ≤ 2.
4. Have primary histologically confirmed T1 and/or high grade tumors and/or CIS.
5. All visible papillary tumors must be completely resected.
6. Early postoperative (within 24 hours of TURBT) single dose chemotherapy is allowed.
7. BCG therapy indication.
8. Never treated with BCG immunotherapy
9. Willing to comply with study visits and procedures as per protocol
10. Use of reliable contraception (see section 8.6) from the screening visit to 30 days after the last RUTI® or placebo injection.

Exclusion Criteria:

1. Life expectancy <5 years.
2. Have a severe concomitant disease that might limit compliance or completion of the protocol.
3. Have any other malignancy that might impact 3-year survival or might be potentially confused with NMIBC.
4. Have other neoplasms.
5. Have congenital or acquired immune deficiencies or under immunomodulatory treatment.
6. Be receiving cytotoxic drugs or systemic corticosteroids within 8 weeks of receiving the first administration of BCG.
7. Have received radiation therapy for their bladder cancer within 4 months prior to study entry.
8. 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.
9. Have biopsy, TURBT, or traumatic catheterization within 14 days of start of intravesical BCG treatment.
10. Have active tuberculosis at screening visit.
11. Active pregnancy or breastfeeding.
12. Soy allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RUTI® injection	Drug: RUTI®; Administration of RUTI®
Placebo Comparator: Sodium Chloride 0.9% injection	Drug: Placebo; Administration of placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Archivel Farma S.L.
• Collaborators: Fundació Institut Germans Trias i Pujol

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2017
• Primary Completion (Actual): January 14, 2020
• Study Completion (Actual): December 22, 2022

Study Registration Dates

• First Submitted: June 9, 2017
• First Submitted That Met QC Criteria: June 16, 2017
• First Posted (Actual): June 19, 2017

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Immunotherapy; NMIBC; Non-muscle invasive bladder cancer; RUTI
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms
• Other Study ID Numbers: RUTIVAC-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No