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

Primary Purpose

High-Risk Non-Muscle-Invasive Bladder Cancer

Status

Completed

Phase

Phase 1

Locations

Spain

Study Type

Interventional

Intervention

RUTI®

Placebo

About this trial

This is an interventional basic science trial for High-Risk Non-Muscle-Invasive Bladder Cancer focused on measuring NMIBC, Immunotherapy, RUTI, Non-muscle invasive bladder cancer

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Germans Trias i Pujol Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

RUTI® injection

Sodium Chloride 0.9% injection

Arm Description

Outcomes

Primary Outcome Measures

Changes in the systemic Th1 immune response.

IFN-γ production assessed by intracellular staining after ex vivo stimulation of PBMCs with PPD

Changes in the local immune response in peritumoral tissue (Th1/Th2 ratio)

Th1/Th2 ratio in cells in the peritumoral tissue

Changes in the local immune response in urine

Urine levels of cytokines by multiplex analysis

Secondary Outcome Measures

Recurrence date

Disease worsening

Disease worsening: events that included diagnosis of T2 or greater

Death

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

From Baseline to BCG administration number 6

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).

Full Information

NCT ID

NCT03191578

First Posted

June 9, 2017

Last Updated

July 13, 2023

Sponsor

Archivel Farma S.L.

Collaborators

Fundació Institut Germans Trias i Pujol

1. Study Identification

Unique Protocol Identification Number

NCT03191578

Brief Title

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

Acronym

RUTIVAC-1

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

June 16, 2017 (Actual)

Primary Completion Date

January 14, 2020 (Actual)

Study Completion Date

December 22, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Archivel Farma S.L.

Collaborators

Fundació Institut Germans Trias i Pujol

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

High-Risk Non-Muscle-Invasive Bladder Cancer

Keywords

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

RUTI® injection

Arm Type

Experimental

Arm Title

Sodium Chloride 0.9% injection

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

RUTI®

Intervention Description

Administration of RUTI®

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administration of placebo

Primary Outcome Measure Information:

Title

Changes in the systemic Th1 immune response.

Description

IFN-γ production assessed by intracellular staining after ex vivo stimulation of PBMCs with PPD

Time Frame

Baseline, Day 10, weeks 2, 7 and 16

Title

Changes in the local immune response in peritumoral tissue (Th1/Th2 ratio)

Description

Th1/Th2 ratio in cells in the peritumoral tissue

Time Frame

Baseline and week 16 visit

Title

Changes in the local immune response in urine

Description

Urine levels of cytokines by multiplex analysis

Time Frame

Baseline, Day 10, weeks 2, 7 and 16

Secondary Outcome Measure Information:

Title

Recurrence date

Description

Recurrence date

Time Frame

Until 3 years since TURBT

Title

Disease worsening

Description

Disease worsening: events that included diagnosis of T2 or greater

Time Frame

Until 3 years since TURBT

Title

Death

Time Frame

Until 3 years since TURBT

Title

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

Description

From Baseline to BCG administration number 6

Time Frame

through study completion an average of 1,5 year

Title

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

Description

Proportion of patients who develop a Grade 3 or 4 systemic reactions (adverse events related to RUTI/placebo).

Time Frame

through study completion an average of 1,5 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

Germans Trias i Pujol Hospital

City

Badalona

State/Province

Barcelona

ZIP/Postal Code

08916

Country

Spain

12. IPD Sharing Statement

Learn more about this trial

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

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