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-BE
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- 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 following TURBT are eligible. Participants with persistent multifocal tumors at screening must undergo a second debulking, re-staging TURBT to reduce the tumor burden. Participants will be ineligible if any individual tumor is >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 =2 audiometric hearing loss
• CTCAE version 5.0 Grade =2 peripheral neuropathy
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
a. A female 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 woman becomes of childbearing potential after start of the study, the woman must comply with point (ii), as described above.
A female participant must also:
• agrees to not donate eggs (ova, oocytes, or freeze for future use) for the purposes of assisted reproduction during the study and for at least 6 months after the last dose of study drug.
• not be breastfeeding and not planning to become pregnant during the study and for at least 6 months after t
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, intra-abdominal 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.
23.Not recovered from adverse events due to a previously administered agent.
24.Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time.
25.Pelvic radiotherapy administered less than 6 months prior to screening.
26.Received a live virus vaccine within 30 days of planned start of study treatment
27.Active autoimmune disease that has required systemic treatment in the past 2 years.
28.Active infection requiring systemic intravenous therapy within 14 days prior to randomization.
29.Received intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/TURBT to starting study treatment.
30.Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
31.Participants with a history of Grade =3 toxic effects when using anti-TNF or anti-IL-6 agents are excluded.
32.Participants still recovering from toxicity of prior anticancer therapy which was received more than 24
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