Guidance of Adjuvant Instillation in Intermediate Risk Non-muscle Invasive Bladder Cancer by Drug Screens in Patient Derived Organoids. A Single Center, Open-label, Phase II Trial With a Feasibility Endpoint. (GAIN-INST-TRIAL)
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Roland Seiler-Blarer
- Enrollment
- 31
- Locations
- 2
- Primary Endpoint
- Proportion of patients with successful drug selection
Study Overview
Brief Summary
From patients with intermediate risk non-muscle invasive bladder cancer tumor (NMIBC) specimens will be harvested during transurethral resection. Fresh specimens will be cultured as patient derived organoids (PDO). After approx. 10 days, PDO are exposed to different drugs that are used as intravesical instillation agents in these patients (epirubicin, mitomycin, gemcitabine, docetaxel). After 2 days of exposure, PDO viability will be measured. The drug with the highest antitumor effect on PDO will be applied as weekly intravesical instillations 6 times. Thereafter, patients are followed according to the standard of care.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥ 18 years
- •Signed Informed Consent Form
- •ECOG performance status of 0 or 1
- •Histologically confirmed intermediate risk non muscle-invasive urothelial carcinoma of the bladder (pTa low grade) Patients
- •Representative fresh tumor specimen for PDO generation and drug screen
Exclusion Criteria
- •Known previous high grade and/or high risk non muscle-invasive bladder cancer
- •Previous Intravesical biological/immuno (BCG) therapy
- •Pregnancy or nursing
- •Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol
- •Severe infection within 4 weeks prior to cycle 1, day 1
- •Contraindication for frequent catheterization
- •Voiding dysfunction
- •Pregnancy or nursing
- •Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 6 months after the last treatment.
- •Male subject who is unwilling to use acceptable method of effective contraception during IP treatment and through 6 months after the last dose of IP.
Arms & Interventions
Mitomycin
Patients in that PDOs show highest response to this drug in-vitro will be treated with Mitomycin.
Intervention: Mitomycin (Drug)
Gemcitabine
Patients in that PDOs show highest response to this drug in-vitro will be treated with Gemcitabine.
Intervention: Gemcitabine (Drug)
Docetaxel
Patients in that PDOs show highest response to this drug in-vitro will be treated with Docetaxel.
Intervention: Docetaxel (Drug)
Epirubicin
Patients in that PDOs show highest response to this drug in-vitro will be treated with Epirubicin.
If no significant drug selection can be performed in-vitro, Epirubicin will be the default for instillation.
Intervention: Epirubicin (Drug)
Outcomes
Primary Outcomes
Proportion of patients with successful drug selection
Time Frame: 24 months
Proportion of patients for which a specific selection of chemotherapeutic agent for intravesical instillation can be determined by using drug screens in PDOs.
Secondary Outcomes
- Proportion of patients for whom patient-derived organoids (PDOs) can be successfully generated (regardless of subsequent drug screen)(24 months)
- Recurrence free survival 24 months after TURBT(24 months)
- Rate of recurrence in the study population(24 months)
- Progression free survival 24 months after TURBT(24 months)
- General quality of Life(24 months)
- Quality of Life related to the bladder cancer(24 months)
- Safety profile of instillations(24 months)
Investigators
Roland Seiler-Blarer
Chairman
Hospital Centre Biel/Bienne