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A Study of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-invasive Bladder Cancer (MIBC) of the Bladder
EU CTIS ID: 2023-507188-21-00
What this study is testing
To compare bladder intact event-free survival (BI-EFS) in participants receiving TAR-200 in combination with cetrelimab versus concurrent chemoradiotherapy.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- ≥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
You likely can't join if
- 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.
See the full eligibility criteria
Who can join
- ≥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 on the options for banking of ova for reproductive Conservation b. Participants must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 6 months after receiving the last dose of study treatment. Partners of participants who can conceive a child, if that partner is of childbearing potential, must also be practicing a highly effective method of contraception. If the participant is vasectomized, they still must wear a condom (with or without spermicidal foam/gel/film/cream/suppository), but their partner is not required to use contraception. A participant must also agree to not donate sperm for the purpose of reproduction during the study and for at least 6 months after the last dose of study treatment, and not plan to conceive a child while enrolled in the study or within 6 months after the last dose of study treatment. Participants should consider preservation of sperm prior to study treatment as anti-cancer treatments may impair fertility. Investigators will advise participants on the options for banking of sperm for reproductive conservation
- Must sign an Informed Consent Form (or their legally acceptable representative must sign) indicating that they understand the purpose of, and procedures required for, the study and is willing to participate in the study and agree to store samples when applicable
What rules you out
- 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.
- Criterion added per Global Amendment 3: Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
- 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.
- Participants must not have evidence of cT4b, or N1-3, or M1 disease based on local radiology staging 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. Participant is eligible if perforation has healed prior to randomization.
- Bladder post-void residual volume >350 mL at screening after second voided urine.
- History of clinically significant polyuria with recorded 24-hour urine volumes greater than 4,000-mL.
- 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.
The study team makes the final eligibility decision.
Where it's taking place
- Mexico
- Japan
- Brazil
- Taiwan
- Korea, Republic of
- India
- China
- Turkey
- Canada
- Argentina
- Russian Federation
- United States
- Ukraine
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Mexico; Japan; Brazil; Taiwan; Korea, Republic of; India and 7 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.