A Study of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-invasive Bladder Cancer (MIBC) of the Bladder
- Conditions
- Muscle-Invasive Urothelial Carcinoma (MIBC) of the BladderMedDRA version: 20.0Level: LLTClassification code: 10046714Term: Urothelial carcinoma bladder Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-507188-21-00
- Lead Sponsor
- Janssen - Cilag International
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 550
=18 years (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent., Participants must be willing and able to adhere to the lifestyle restrictions specified in this protocol, Histologically proven, cT2-T4a N0, M0 urothelial carcinoma of the bladder. Initial diagnosis must have been within 120 days of randomization date. Participants with variant histologic subtypes (e.g. squamous cell carcinoma) are allowed if urothelial (transitional cell) differentiation is predominant. However, the presence of small cell or neuroendocrine variants will make a participant ineligible., 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 CTCAE version 5.0 Grade = 2 prior to randomization, Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2, Thyroid function tests are within the normal range per investigator assessment (or stable on hormone supplementation). 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: a. Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding 2 weeks): i. Absolute neutrophil count (ANC) = 1,500/mm^3 ii. Platelet count =80,000/mm^3 iii. Hemoglobin =9.0 g/dL b. Liver function: i. Total bilirubin =1.5 x ULN OR direct bilirubin =ULN for participants with total bilirubin levels >1.5xULN (except participants with Gilbert's Syndrome, who must have a total bilirubin < 3.0 mg/dL), ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5x institutional ULN c. Renal function: Creatinine clearance =30 mL/min using the CockcroftGault formula. 24-hour creatinine clearance test will also be accepted for estimating renal function in situations where Cockcroft-Gault formula is not a good predictor of estimating adequate renal function. Note: If cisplatin is chosen as the radio-sensitizing agent, creatinine clearance must be =50 mL/min, Contraceptive use by participants should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies. Investigators will advise participants on the options for banking of sperm and ova, for reproductive conservation. a. A participant must be either of the following: i. Not of childbearing potential ii. Of childbearing potential and practicing true abstinence, or have a sole partner who is vasectomized, or practicing at least 1 highly effective user independent method of contraception. Participant must agree to continue the above throughout the study and for 6 months after the last dose of study treatment. Note: If a participant becomes of childbearing potential after start of the study, the participant must comply with point (ii), as described above. A participant must also agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 6 months after the last dose of study treatment, and not be breastfeeding and not planning to become pregnant during the study and for at least 6 months after the last dose of study treatment. Participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility. Investigators will advise participants o
Active malignancies other than the disease being treated under study., Received intervening serial intravesical chemotherapy or immunotherapy from the time of pre-screening (diagnostic) or screening (completion) cystoscopy/Transurethral Resection of Bladder Tumor to starting study treatment. Peri-operative intravesical chemotherapy prior to study treatment is allowed per institutional guidelines, Prior therapy with an anti-programmed cell death 1, anti-PD-ligand agent, or with an agent directed to another co-inhibitory T-cell receptor., Participants with a history of Grade =3 toxic effects when using antiTNF or anti-IL-6 agents., Received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment or not recovered from adverse events due to a previously administered agent. Participants with a history of prior pelvic radiotherapy are excluded, An active autoimmune disease that has required systemic treatment in the past 2 years are excluded., Received a live virus vaccine within 30 days prior to he initiation of study treatment. Inactivated (non-live or non-replicating) vaccines approved or authorized for emergency use (eg, COVID 19) by local health authorities are allowed., Active infection requiring systemic IV therapy within 14 days prior to randomization., A pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted if it does not interfere with placement or retention of TAR-200 in the bladder. Participants with unilateral hydronephrosis are permitted; however, participants with bilateral hydronephrosis are excluded., Indwelling urinary catheters are not permitted; however, intermittent catheterization is acceptable., Participants who require immunosuppressive medications including but not limited to systemic corticosteroid at doses >10 mg/day of prednisone or its equivalence, methotrexate, cyclosporine, azathioprine, and TNF-alpha blockers. Use of immunosuppressive medications for the management of immune related adverse events, infusion related reactions, or in participants with contrast allergies is acceptable. Use of inhaled, topical, and intranasal corticosteroids are permitted., Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder., Must not have clinically significant liver disease that precludes participant treatment regimens prescribed on the study, Human immunodeficiency virus (HIV) infection, unless the participant has been on a stable anti-retroviral therapy regimen for the last 6 months or more and has had no opportunistic infections and a CD4 count of >350 in the last 6 months., Active hepatitis B or C infection, Concurrent urinary tract infection that cannot be cleared with antibiotic therapy, History of uncontrolled cardiovascular disease including any of the following in the 3 months prior to screening: a. unstable angina, b. myocardial infarction, c. ventricular fibrillation, d. Torsades de Pointes, e. cardiac arrest, or known congestive New York Heart Association Class III-IV heart failure, f. cerebrovascular accident, g. transient ischemic attack; h. pulmonary embolism or other venous thromboembolism, Criterion added per Global Amendment 3: The participant is unable to comply with the requirements of this protocol, including any factors that are likely to affect the participant's return for scheduled visits and follow-up., Criteri
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method