A Phase 3, Randomized Study Evaluating the Efficacy and Safety of TAR-210 Erdafitinib Intravesical Delivery System Versus Single Agent Intravesical Chemotherapy in Participants With Intermediate-risk Non-muscle Invasive Bladder Cancer (IR-NMIBC) and Susceptible FGFR Alterations
Overview
- Phase
- Phase 3
- Intervention
- TAR-210
- Conditions
- Not specified
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 641
- Locations
- 372
- Primary Endpoint
- Disease Free Survival (DFS)
- Status
- Recruiting
- Last Updated
- 19 days ago
Overview
Brief Summary
The main purpose of this study is to compare the disease-free survival between participants receiving treatment with TAR-210 versus investigator's choice of intravesical chemotherapy for treatment of intermediate-risk NMIBC.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Main study only: Have a histologically confirmed diagnosis (within 90 days of randomization) of IR-NMIBC with at least one of the following criteria fulfilled: a. Ta low grade (LG)/ Grade 1 (G1): primary or recurrent, b. Ta LG/G2: primary or recurrent and c. Greater than or equal to (\>=) 1 of the following risk factors: i. Multiple Ta LG tumors, ii. Solitary LG tumor \>= 3 cm, iii. Early recurrence (less than \[\<\] 1 year), iv. Frequent recurrence (greater than \[\>\] 1 per year), v. Recurrence after prior adjuvant intravesical treatment (single perioperative dose of chemotherapy does not fulfill this risk factor)
- •Substudy only: Have a histologically confirmed new diagnosis (within 90 days of randomization) of IR-NMIBC for whom MMC is deemed the therapy of choice according to local standard of care with at least 1 of the following criteria fulfilled: a. Ta LG/G1, b. Ta LG/G2, and \>=1 of the following risk factors: i) Multiple Ta LG tumors, ii) Solitary LG tumor \>=3 cm
- •Have a susceptible fibroblast growth factor receptor (FGFR) mutation or fusion either by urine testing or tumor tissue testing (from TURBT tissue), as determined by central or local testing
- •Participants must be willing to undergo all study procedures (e.g., multiple cystoscopies from Screening through the end of study and TURBT for assessment of recurrence/progression) and receive the assigned treatment, including intravesical chemotherapy if randomized into that arm.
- •Visible papillary disease must be fully resected prior to randomization and absence of disease must be documented at Screening cystoscopy
- •Can have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment
- •Have an Eastern Cooperative Oncology Group performance status of 0 to 2
Exclusion Criteria
- •Known allergies, hypersensitivity, or intolerance to any study component or its excipients, including: a. Erdafitinib excipients; b.TAR-210 drug delivery system constituent materials ; c. urinary placement catheter materials; d. MMC or chemically related drugs; e. Gemcitabine or chemically related drugs
- •Presence of any bladder or urethral anatomic feature (that is, urethral stricture) that, in the opinion of the investigator, may prevent the safe insertion, indwelling use, removal of TAR-210 or passage of a urethral catheter for intravesical chemotherapy
- •Polyuria with recorded 24-hour urine volumes \> 4000 milliliters (mL)
- •Current indwelling urinary catheters, however, intermittent catheterization is acceptable
- •Had major surgery or had significant traumatic injury and/or not fully recovered within 4 weeks before first dose (TURBT is not considered major surgery)
- •\- Previous diagnosis of histologically confirmed urothelial bladder carcinoma at any time prior to current qualifying diagnosis
Arms & Interventions
Substudy: Group A: TAR-210
Participants in Group A will have TAR-210 inserted in the bladder on Day 1 and removed after 12 weeks. One TAR-210 will be inserted every 12 weeks over a treatment period of approximately 1 year.
Intervention: TAR-210
Main Study: Group A: TAR-210
Participants in Group A will have TAR-210 inserted in the bladder on Day 1 and removed after 12 weeks. One TAR-210 will be inserted every 12 weeks over a treatment period of approximately 1 year.
Intervention: TAR-210
Main Study: Group B: MMC or Gemcitabine
Participants in Group B will receive intravesical mitomycin C (MMC) or gemcitabine (investigator's choice) once weekly for 4 to 6 induction doses followed by a maintenance phase for a minimum of 6 months and up to 1 year.
Intervention: Gemcitabine
Substudy: Group B: MMC
Participants in substudy Group B will receive intravesical MMC once weekly for 4 to 6 induction doses followed by a maintenance phase for a minimum of 6 months and up to 1 year.
Intervention: MMC
Main Study: Group B: MMC or Gemcitabine
Participants in Group B will receive intravesical mitomycin C (MMC) or gemcitabine (investigator's choice) once weekly for 4 to 6 induction doses followed by a maintenance phase for a minimum of 6 months and up to 1 year.
Intervention: MMC
Outcomes
Primary Outcomes
Disease Free Survival (DFS)
Time Frame: From randomization to the date of the first documented recurrence, disease progression or death (approximately 4 years and 2 months)
DFS is measured as the time from randomization to the date of the first documented recurrence of Ta non-muscle invasive bladder cancer (NMIBC) of any grade, disease progression, or death due to any cause, whichever occurs first.
Secondary Outcomes
- European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire for Non muscle Invasive Bladder Cancer (EORTC-QLQ-NMIBC24) Scores(Baseline, Weeks 6, 12, 24, 36, and 48)
- Time to next Treatment (TTNT)(From randomization to the date of first documented subsequent treatment (local, systemic, surgical, or interventional) for bladder cancer (approximately 4 years and 2 months))
- High Grade Recurrence-free Survival (HG RFS)(From randomization to the date of first documented evidence of HG NMIBC or death (approximately 4 years and 2 months))
- Progression Free Survival (PFS)(From randomization to the date of first documented disease progression or death (approximately 4 years and 2 months))
- Number of Participants With Adverse Events (Including Physical Examination, Vital Signs and Laboratory Abnormalities)(From first dose up to 30 days after last dose of study treatment (approximately 4 years and 2 months))
- Overall Survival (OS)(From randomization to the date of death (approximately 4 years and 2 months))
- European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire Core-30 items (EORTC-QLQ-C30) Scores(Baseline, Weeks 6, 12, 24, 36, and 48)
- Percentage of Participants With Significant Change From Baseline in EORTC-QLQ-C30 Scores(Weeks 6, 12, 24, 36, and 48)
- Percentage of Participants With Significant Change From Baseline in EORTC-QLQ-NMIBC24 Scores(Weeks 6, 12, 24, 36, and 48)
- Number of Diagnostic and Therapeutic Invasive Urological Interventions after Study Treatment(From study treatment completion up to trial discontinuation (approximately 4 years and 2 months))