A Study of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-invasive Bladder Cancer (MIBC) of the Bladder
Purpose
The purpose of study is to compare bladder intact-event free survival (BI-EFS) in participants receiving TAR-200 in combination with intravenous (IV) cetrelimab versus concurrent chemoradiotherapy.
Condition
- Urinary Bladder Neoplasms
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Ineligible for or have elected not to undergo radical cystectomy - All adverse events associated with any prior surgery and/or intravesical therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade less than (<) 2 prior to randomization - Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2 - Thyroid function tests within normal range or stable on hormone supplementation per investigator assessment. Investigators may consult an endocrinologist for participant eligibility assessment in the case of equivocal or marginal test results - Adequate bone marrow, liver, and renal function: Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding two weeks): Absolute neutrophil count (ANC) greater than or equal to (>=) 1,500/cubic millimeters (mm^3); Platelet count >=80,000/mm^3; Hemoglobin >=9.0 grams per deciliter (g/dL); Liver function: (Total bilirubin less than or equal to (<=) 1.5 * upper limit of normal (ULN) or direct bilirubin <= ULN for participants with total bilirubin levels greater than (>)1.5*ULN (except participants with Gilbert's Syndrome, who must have a total bilirubin < 3.0 mg/dL), and Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (<=) 2.5* institutional ULN); Renal function: Creatinine clearance >=30 mL/min using the Cockcroft-Gault formula
Exclusion Criteria
- Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder. Ta/T1/Carcinoma in situ (CIS) of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to initiating study - Must not have diffuse CIS based on cystoscopy and biopsy. Diffuse, or multi-focal, CIS is defined as the presence of at least 4 distinct CIS lesions in the bladder at the time of the Screening re-TURBT - Participants must not have evidence of cT4b, or N1-3, or M1 disease based on local radiology staging (chest, abdomen, and pelvis must be performed using Computed tomography [CT] or Magnetic resonance imaging [MRI]) within 42 days prior to randomization - Presence of any bladder or urethral anatomic feature that, in the opinion of the investigator, may prevent the safe placement, indwelling use, or removal of TAR 200 - Evidence of bladder perforation during diagnostic cystoscopy
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental TAR-200 + Cetrelimab |
Participants will receive intravesical TAR-200 every 3 weeks (21 days indwelling) for first 18 weeks and thereafter from Week 24 every 12 weeks through study Year 3 in combination with intravenous (IV) Cetrelimab. |
|
|
Active Comparator Chemotherapy (cisplatin or gemcitabine) + Radiation Therapy |
Participants will receive chemotherapy based on investigator's choice from either cisplatin intravenously once weekly for 6 treatment weeks or gemcitabine intravenously twice weekly for 6 treatment weeks as Standard of Care (SOC) along with radiation therapy from either conventional radiotherapy (64 Gray [Gy], bladder only) for up to 6.5 treatment weeks or hypo-fractionated radiotherapy (55 Gy, bladder only) for up to 4 weeks. |
|
Recruiting Locations
University of Texas Medical Branch
League City, Texas 77573
League City, Texas 77573
More Details
- Status
- Recruiting
- Sponsor
- Janssen Research & Development, LLC
Detailed Description
The TAR-200 is an investigational intravesical drug delivery system. Cetrelimab (JNJ-63723283) is a fully human immunoglobulin G4 (IgG4) kappa monoclonal antibody (mAb) that binds programmed cell death protein 1 (PD-1). Study consists of screening phase of 42 days, treatment phase and follow up phase. The total duration of study will be up to 8 years. Efficacy evaluation includes disease assessment (Cystoscopy/TURBT Biopsy/Pathology) and Patient Reported Outcomes (Quality of Life Assessments) and safety assessments includes vital sign measurements, 12-lead electrocardiogram (ECG), physical examinations, clinical laboratory tests, cystoscopic examination, anti-drug antibody (ADA) assessments, concomitant treatments/procedures and adverse event monitoring.