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

Phase 1
Completed
Conditions
High-Risk Non-Muscle-Invasive Bladder Cancer
Interventions
Drug: Placebo
Registration Number
NCT03191578
Lead Sponsor
Archivel Farma S.L.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
44
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
RUTI® injectionRUTI®-
Sodium Chloride 0.9% injectionPlacebo-
Primary Outcome Measures
NameTimeMethod
Changes in the systemic Th1 immune response.Baseline, Day 10, weeks 2, 7 and 16

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

Changes in the local immune response in urineBaseline, Day 10, weeks 2, 7 and 16

Urine levels of cytokines by multiplex analysis

Changes in the local immune response in peritumoral tissue (Th1/Th2 ratio)Baseline and week 16 visit

Th1/Th2 ratio in cells in the peritumoral tissue

Secondary Outcome Measures
NameTimeMethod
Proportion of patients who develop a Grade 3 or 4 systemic reactionsthrough study completion an average of 1,5 year

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

Disease worseningUntil 3 years since TURBT

Disease worsening: events that included diagnosis of T2 or greater

Recurrence dateUntil 3 years since TURBT

Recurrence date

DeathUntil 3 years since TURBT
Proportion of patients who develop a Grade 3 or 4 local reactionsthrough study completion an average of 1,5 year

From Baseline to BCG administration number 6

Trial Locations

Locations (1)

Germans Trias i Pujol Hospital

🇪🇸

Badalona, Barcelona, Spain

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