Brief Summary
The purpose of this study is to evaluate the anti-tumor effects of TAR-200 in combination with intravenous (IV) cetrelimab and IV cetrelimab alone.
Brief Title
A Study of TAR-200 in Combination With Cetrelimab and Cetrelimab Alone in Participants With Muscle-Invasive Urothelial Carcinoma of the Bladder
Detailed Description
Bladder cancer is the tenth most common malignancy worldwide. Approximately 25 percent (%) of all new bladder cancer participants present with muscle invasive bladder cancer (MIBC) at the time of diagnosis, and roughly 50% will ultimately develop distant metastases. The TAR-200/ gemcitabine (JNJ-17000139) product is an intravesical drug delivery system regulated as an investigational drug. The drug constituent consists of gemcitabine minitablets and osmotic minitablets. Cetrelimab (JNJ-63723283) is a fully human immunoglobulin G4 (IgG4) kappa monoclonal antibody (mAb) that binds programmed-cell death protein (PD)-1. The standard of care in MIBC includes radical cystectomy (RC) with urinary diversion and is considered the preferred treatment option for participants who are considered surgical candidates. Study consists of a Screening phase, Treatment phase and follow-up phase. The total duration of study will be up to 2 years and 6 months. Efficacy, safety, pharmacokinetics (PK), and biomarkers will be assessed at specific time points during this study.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Urinary Bladder Neoplasms
Eligibility Criteria
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
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
* 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
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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04919512
Org Class
Industry
Org Full Name
Janssen Research & Development, LLC
Org Study Id
CR109044
Overall Status
Active, not recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
pCR was defined as percentage of participants who achieved complete pathologic response. Complete pathologic response is defined as ypT0N0 (no evidence of disease) as assessed by pathologic evaluation on radical cystectomy (RC) specimen. pCR was determined by central pathologic review.
Outcome Measure
Pathologic Complete Response (pCR) Rate
Outcome Time Frame
At Week 12
Secondary Ids
Secondary Id
17000139BLC2002
Secondary Id
2020-005565-13
Secondary Outcomes
Outcome Time Frame
Cycle Day 1 up to Week 124
Outcome Measure
Number of Participants With Treatment Emergent Adverse Event According to Common Terminology Criteria for Adverse Event (CTCAE) Version 5 Grades
Outcome Time Frame
Cycle Day 1 up to Week 124
Outcome Measure
Number of Participants With Worst Post-baseline Laboratory Values Based on Common Terminology Criteria for Adverse Events (CTCAE)
Outcome Time Frame
Cycle Day 1 up to Week 124
Outcome Measure
Recurrence-Free Survival (RFS)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ahmed Aboumohamed
Investigator Email
aaboumoh@montefiore.org
Categories Mesh Debug
Prostate Cancer --- UROGENITAL NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Kidney & Urinary Tract --- URINARY BLADDER DISEASES
Kidney & Urinary Tract --- UROLOGIC DISEASES
MeSH Terms
URINARY BLADDER NEOPLASMS
UROLOGIC NEOPLASMS
UROGENITAL NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
FEMALE UROGENITAL DISEASES
FEMALE UROGENITAL DISEASES AND PREGNANCY COMPLICATIONS
UROGENITAL DISEASES
URINARY BLADDER DISEASES
UROLOGIC DISEASES
MALE UROGENITAL DISEASES