A Phase 3, Multi-center, Randomized Study Evaluating Efficacy of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-Invasive Urothelial Carcinoma (MIBC) of the Bladder who are not Receiving Radical Cystectomy
- Conditions
- Muscle-Invasive Urothelial Carcinoma (MIBC) of the BladderMedDRA version: 20.0Level: LLTClassification code 10046714Term: Urothelial carcinoma bladderSystem Organ Class: 100000004864MedDRA version: 21.0Level: LLTClassification code 10046720Term: Urothelial carcinoma bladder stage IISystem Organ Class: 100000004864MedDRA version: 21.0Level: LLTClassification code 10046721Term: Urothelial carcinoma bladder stage IIISystem Organ Class: 100000004864MedDRA version: 21.0Level: LLTClassification code 10046722Term: Urothelial carcinoma bladder stage IVSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-002620-36-IT
- Lead Sponsor
- JANSSEN CILAG INTERNATIONAL NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 550
1. > =18 years (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent
2. Histologically proven, cT2-T4a N0, M0 infiltrating urothelial carcinoma of the bladder. Diagnosis must have been within 90 days of randomization date. Participants with variant histologic subtypes (e.g. squamous cell carcinoma) are allowed if urothelial (transitional cell) differentiation is predominant (e.g. 20% variant histologic subtype). However, the presence of any neuroendocrine, micropapillary, signet ring cell, plasmacytoid, or sarcomatoid features will make a participant ineligible
3. Ineligible for or have elected not to undergo radical cystectomy.
4. 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
5. Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
6. Thyroid function tests within normal range or stable on hormone supplementation per investigator assessment.
7. Adequate bone marrow, liver, and renal function:
a. Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding two weeks):
i. Absolute neutrophil count (ANC) = 1,000/mm^3
ii. Platelet count =75,000/mm^3
iii. Hemoglobin =8.0 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 >40 mL/min either directly measured via 24-hour urine collection, calculation using the Cockcroft-Gault formula, or
calculation for the Modification of Diet in Renal Disease for adult participants.
8. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies.
Please see the protocol for all inclusion criteria
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 165
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 385
1. Active malignancies other than the disease being treated under study.
2. Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder.
3. Must not have diffuse carcinoma in situ 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.
4. Participants must not have evidence of cT4b, or N1-3, or M1 disease based on local radiology staging within 42 days prior to randomization.
5. 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.
6. Evidence of bladder perforation during diagnostic cystoscopy.
7. Bladder post-void residual volume >350 mL at screening after second voided urine.
8. History of clinically significant polyuria with recorded 24-hour urine volumes greater than 4,000-mL.
9. Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to randomization.
10. Received intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/Transurethral Resection of Bladder Tumor to starting study treatment.
11. Prior therapy with an anti-programmed cell death 1, anti-PD-ligand 2 agent, or with an agent directed to another co-inhibitory T-cell receptor.
12. Participants with a history of Grade =3 toxic effects when using anti-TNF or anti-IL-6 agents.
13. 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.
14. An active, known or suspected autoimmune disease.
15. Received a live virus vaccine within 30 days prior to planned start of study treatment.
16. Active infection requiring systemic therapy within 14 days prior to randomization.
17. Has had an allogeneic tissue/solid organ transplant.
18. 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.
19. Indwelling urinary catheters are not permitted; however, intermittent catheterization is acceptable.
20. 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.
21. Must not have clinically significant liver disease that precludes participant treatment regimens prescribed on the study
Please see the protocol for all exclusion criteria
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