A Phase 2, Open-Label, Multi-Center, Randomized Study of TAR-200 in Combination with Cetrelimab and Cetrelimab Alone in Participants with Muscle-Invasive Urothelial Carcinoma of the Bladder who are Scheduled for Radical Cystectomy and are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy
- Conditions
- Muscle-Invasive Urothelial Carcinoma 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
- EUCTR2020-005565-13-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
- 160
1. >=18 years (or the legal age of consent in the jurisdiction in which the study is taking place)
2. Histologically proven, cT2-T4a N0, M0 infiltrating urothelial carcinoma (AJCC 2017) of the bladder. Initial diagnosis must have been within 90 days of randomization date. Participants with variant histologic subtypes (eg squamous differentiation) are allowed if urothelial differentiation is predominant (eg, <20% variant histologic subtype).
3. Participants with an individual intravesical tumor size of 3 cm.
4. Deemed eligible for and willing to undergo RC by the attending urologist.
5 Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 or 1
6.Thyroid function tests within normal range or stable on hormone supplementation per Investigator assessment.
7. Adequate bone marrow, liver, and renal function (kindly refer to study protocol for further details)
8. Participants must refuse cisplatin-based combination chemotherapy (and understand the risk and benefits of doing so) or be deemed ineligible for cisplatin-based chemotherapy by meeting at least one of the following criteria:
• GFR <60 mL/min/1.73 m2 (assessed using the CKD-EPI equation)
• Common Terminology Criteria for Adverse Events (CTCAE) version
5.0 Grade • CTCAE version 5.0 Grade 9. Prior systemic chemotherapy for indications other than urothelial cell carcinoma of the bladder is permitted, but interval between this treatment and study enrollment must exceed 24 months. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (NCI-CTCAE version 5.0) or baseline before administration of study drug. Participants with toxicities attributed to prior anticancer therapy which are not expected to resolve and result in long lasting sequelae, such as peripheral neuropathy after platinum-based therapy or audiometric hearing loss, are ineligible.
10.All adverse events associated with any prior surgery must have resolved to CTCAE version 5.0 Grade <2 prior to randomization.
11.Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
12.A female participant of childbearing potential must have a negative serum or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study, that may exceed those listed in the Schedule of
Activities
13.Must sign an informed consent form (ICF) (or their legally acceptable representative must sign)
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 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
1.Active malignancies other than the disease being treated under study. 2.Must not have received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 years prior to starting study treatment
3.Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder.
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.Uncontrolled adrenal insufficiency.
7.A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4,000 mL.
8.History of uncontrolled cardiovascular disease
9.Must not have active tuberculosis.
10.Has had an allogeneic tissue/solid organ transplant.
11.Pyeloureteral tube externalized to the skin is exclusionary.
12.Indwelling catheters are not permitted;
13.Participants with an active, known or suspected autoimmune disease.
14.Participants must not have clinically significant liver disease that
precludes participant treatment regimens prescribed on the study
15.Known human immunodeficiency virus infection.
16.Evidence of active hepatitis B or C infection
17.Concurrent urinary tract infection, defined as a symptomatic infection with a positive urine culture with a bacterial count of =105 colony forming units /mL in urine voided from women, or >104 CFU/mL in urine voided from men, or in straight-catheter urine from women.
18.Active, uncontrolled urogenital bacterial, viral or fungal infections, including UTI. Skin/nail fungal infections are not exclusionary.
19.Evidence of interstitial lung disease or active non-infectious pneumonitis.
20.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
21.Participants who have had a history of acute diverticulitis, intraabdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
22.Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions.
(Kindly refer Protocol section 5.2 Exclusion Criteria for detailed information)
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