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

NCT03191578 | Completed Phase 1

• 1 other identifier: RUTIVAC-1
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

High-Risk Non-Muscle-Invasive Bladder Cancer

Keywords

NMIBC; Immunotherapy; RUTI; Non-muscle invasive bladder cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Recurrence date

  Until 3 years since TURBT

• Disease worsening

  Until 3 years since TURBT

• Death

  Until 3 years since TURBT

• Proportion of patients who develop a Grade 3 or 4 local reactions

  through study completion an average of 1,5 year

• Proportion of patients who develop a Grade 3 or 4 systemic reactions

  through study completion an average of 1,5 year

Study Arms (2)

RUTI® injection

EXPERIMENTAL

Drug: RUTI®

Sodium Chloride 0.9% injection

PLACEBO COMPARATOR

Drug: Placebo

Interventions

RUTI® DRUG

Administration of RUTI®

RUTI® injection

Placebo DRUG

Administration of placebo

Sodium Chloride 0.9% injection

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Archivel Farma S.L.: lead
• Fundació Institut Germans Trias i Pujol: collaborator

Study Sites (1)

Germans Trias i Pujol Hospital

Badalona, Barcelona, 08916, Spain

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2017
• First Posted: June 19, 2017
• Study Start: June 16, 2017
• Primary Completion: January 14, 2020
• Study Completion: December 22, 2022
• Last Updated: July 14, 2023

Record last verified: 2023-07

Locations

ES (1)