A Phase II, 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
Study Identifier:
17000139BLC2002
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Study Complete
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Study Summary
To evaluate the anti-tumor effects of TAR-200 in combination with cetrelimab and cetrelimab alone.
To evaluate efficacy, safety, pharmacokinetics (PK), and biomarkers of TAR-200 in combination with cetrelimab and cetrelimab alone in patients with muscle invasive bladder cancer (MIBC)
To assess the efficacy and safety of neoadjuvant TAR-200 + systemic cetrelimab (CET [anti–programmed death-1 antibody]) vs neoadjuvant CET alone in pts with MIBC scheduled for RC who are ineligible for or refuse neoadjuvant PBC.
To assess the efficacy and safety of neoadjuvant TAR-200 + CET (anti-PD-1) or CET alone in pts with MIBC scheduled for RC who are ineligible/refusing NAC.
Medical Condition
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Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
II
Sex
Female & Male
Age
18+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Study Complete
Requirements information
Inclusion criteria
- Histologically proven, cT2-T4a N0, M0 infiltrating urothelial carcinoma of the bladder. Initial diagnosis must have been within 120 days of randomization date. Participants with variant histologic subtypes are allowed if tumor(s) demonstrate urothelial predominance. However, the presence of small cell or neuroendocrine variants will make a participant ineligible
- Participants with no residual tumor, or intravesical tumor size of less than or equal to (<=)3 centimeter (cm) following transurethral resection of bladder tumor (TURBT) are eligible; debulking TURBT for any residual disease is encouraged but not mandated. Participants with persistent tumors greater than (>)3 cm at screening must undergo a second debulking, re-staging TURBT. Participants will be ineligible if any individual tumor is >3 cm after debulking TURBT
- Deemed eligible for and willing to undergo RC by the operating urologist
- Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 or 1
- Thyroid function tests within normal range or stable on hormone supplementation per investigator assessment. Investigators may consult an endocrinologist for participant eligibility assessment in the case of equivocal or marginal tests results
- All adverse events associated with any prior surgery must have resolved to common terminology criteria for adverse events (CTCAE) version 5.0 Grade less than (<) 2 prior to randomization
- 1. >or= 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 m^2 (assessed using the CKD-EPI equation)
- • Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade >or= 2 audiometric hearing loss
- • CTCAE version 5.0 Grade >or= 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 the last dose of study drug
- b. A male participant 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. His female partner, if of childbearing potential, must also be practicing a highly effective method of contraception
- If the male participant is vasectomized, he still must wear a condom (with or without spermicidal foam/gel/film/cream/suppository), but his female partner is not required to use contraception.
- A male participant must also:
- • agree to not donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after the last dose of study drug
- • not plan to father a child while enrolled in this study or within 6 months after the last dose of study drug
- 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)
Exclusion criteria
- Must not have received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment Participants must not have evidence of cT4b, or N1-3, or M1 disease based on central radiology staging (chest, abdomen, and pelvis must be performed using computed tomography [CT] or magnetic resonance imaging [MRI]) 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 Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to enrollment Participants with evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has resolved prior to dosing 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 months prior to enrollment (except toxicities which are not clinically significant such as alopecia, skin discoloration). 33.Participants who require immunosuppressive medications 34.Participants with a history of allergy to protein-based therapies and participants with a history of any significant drug allergy are excluded. 35.Known hypersensitivity to any study component including: a.Gemcitabine (or other drug excipients) or chemically-related drugs, b.TAR-200 device constituent materials, c.TAR-200 Urinary Placement Catheter materials, d.Cetrelimab excipients or chemically-related drugs Refer to the TAR-200 IB and cetrelimab IB for complete information on excipients. 36.Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to enrollment. 37.Participants with evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has resolved prior to dosing. 38.Bladder post-void residual (PVR) volume >350mL at screening after second voided urine. 39.Participants who have not recovered from the effects of major surgery or significant traumatic injury at least 14 days before randomization (Kindly refer Protocol section 5.2 "Exclusion Criteria" for detailed information)
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Carolinas
Myrtle Beach, SC, United States, 29572
Investigator
Neal Shore
Status
Recruitment Complete
Condition(s) Treated at Site
Bladder