Brief Summary
The purpose of study is to compare bladder intact-event free survival (BI-EFS) in participants receiving TAR-200 in combination with intravenous (IV) cetrelimab versus concurrent chemoradiotherapy.
Brief Title
A Study of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-invasive Bladder Cancer (MIBC) of the Bladder
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Urinary Bladder Neoplasms
Eligibility Criteria
Inclusion Criteria:
* 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 Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade less than (\<) 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: Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding two weeks): Absolute neutrophil count (ANC) greater than or equal to (\>=) 1,500/cubic millimeters (mm\^3); Platelet count \>=80,000/mm\^3; Hemoglobin \>=9.0 grams per deciliter (g/dL); Liver function: (Total bilirubin less than or equal to (\<=) 1.5 \* upper limit of normal (ULN) or direct bilirubin \<= ULN for participants with total bilirubin levels greater than (\>)1.5\*ULN (except participants with Gilbert's Syndrome, who must have a total bilirubin \< 3.0 mg/dL), and Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (\<=) 2.5\* institutional ULN); Renal function: Creatinine clearance \>=30 mL/min using the Cockcroft-Gault 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
Exclusion Criteria:
* Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder. Ta/T1/Carcinoma in situ (CIS) of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to initiating study
* Must not have diffuse CIS 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 (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
* Evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has healed prior to randomization
* 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 Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade less than (\<) 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: Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding two weeks): Absolute neutrophil count (ANC) greater than or equal to (\>=) 1,500/cubic millimeters (mm\^3); Platelet count \>=80,000/mm\^3; Hemoglobin \>=9.0 grams per deciliter (g/dL); Liver function: (Total bilirubin less than or equal to (\<=) 1.5 \* upper limit of normal (ULN) or direct bilirubin \<= ULN for participants with total bilirubin levels greater than (\>)1.5\*ULN (except participants with Gilbert's Syndrome, who must have a total bilirubin \< 3.0 mg/dL), and Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (\<=) 2.5\* institutional ULN); Renal function: Creatinine clearance \>=30 mL/min using the Cockcroft-Gault 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
Exclusion Criteria:
* Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder. Ta/T1/Carcinoma in situ (CIS) of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to initiating study
* Must not have diffuse CIS 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 (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
* Evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has healed prior to randomization
Inclusion Criteria
Inclusion Criteria:
* 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 Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade less than (\<) 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: Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding two weeks): Absolute neutrophil count (ANC) greater than or equal to (\>=) 1,500/cubic millimeters (mm\^3); Platelet count \>=80,000/mm\^3; Hemoglobin \>=9.0 grams per deciliter (g/dL); Liver function: (Total bilirubin less than or equal to (\<=) 1.5 \* upper limit of normal (ULN) or direct bilirubin \<= ULN for participants with total bilirubin levels greater than (\>)1.5\*ULN (except participants with Gilbert's Syndrome, who must have a total bilirubin \< 3.0 mg/dL), and Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (\<=) 2.5\* institutional ULN); Renal function: Creatinine clearance \>=30 mL/min using the Cockcroft-Gault 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
* 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 Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade less than (\<) 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: Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding two weeks): Absolute neutrophil count (ANC) greater than or equal to (\>=) 1,500/cubic millimeters (mm\^3); Platelet count \>=80,000/mm\^3; Hemoglobin \>=9.0 grams per deciliter (g/dL); Liver function: (Total bilirubin less than or equal to (\<=) 1.5 \* upper limit of normal (ULN) or direct bilirubin \<= ULN for participants with total bilirubin levels greater than (\>)1.5\*ULN (except participants with Gilbert's Syndrome, who must have a total bilirubin \< 3.0 mg/dL), and Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (\<=) 2.5\* institutional ULN); Renal function: Creatinine clearance \>=30 mL/min using the Cockcroft-Gault 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
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
NCT04658862
Org Class
Industry
Org Full Name
Janssen Research & Development, LLC
Org Study Id
CR108917
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 3, Multi-center, Randomized Study Evaluating Efficacy of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-Invasive Urothelial Carcinoma (MIBC) of the Bladder Who Are Not Receiving Radical Cystectomy
Primary Outcomes
Outcome Description
Time from randomization to the first BI-EFS event includes histologically proven presence of muscle-invasive bladder cancer (MIBC), clinical evidence of nodal or metastatic disease (as assessed by RECIST 1.1 criteria), radical cystectomy (RC), or death due to any cause.
Outcome Measure
Time from Randomization to the First Bladder Intact Event-free Survival (BI-EFS) event
Outcome Time Frame
Up to 8 years
Secondary Ids
Secondary Id
17000139BLC3001
Secondary Id
2020-002620-36
Secondary Id
2023-507188-21-00
Secondary Outcomes
Outcome Description
MFS is measured from time from randomization to first radiologic (as assessed by RECIST 1.1 criteria) evidence of metastatic disease or death due to any cause.
Outcome Time Frame
Up to 8 years
Outcome Measure
Metastasis-free survival (MFS)
Outcome Description
OS is defined as time from randomization to death.
Outcome Time Frame
Up to 8 years
Outcome Measure
Overall Survival (OS)
Outcome Description
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR). CR is defined as Negative biopsy, and Computed tomography/Magnetic resonance imaging (CT/MRI) showing no evidence of locally advanced or metastatic disease. PR (down-staging) is defined as biopsy proven non-muscle invasive disease (Ta, T1, Tis) and CT/MRI showing no evidence of locally advanced or metastatic disease. Non-Response (NR) includes those not achieving a CR or PR. Those who do not undergo a biopsy will be considered Non-Evaluable (NE).
Outcome Time Frame
Up to 8 years
Outcome Measure
Overall Response Rate (ORR)
Outcome Description
Number of Participants with AEs by Severity as assessed by CTCAE version 5 will be reported. Grade refers to the severity of the AE as follows: Grade 1- Mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2- Moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental Activities of Daily Living (ADL); Grade 3- Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self-care ADL; Grade 4- Life-threatening consequences, urgent intervention indicated; Grade 5- Death related to AE.
Outcome Time Frame
Up to 8 years
Outcome Measure
Number of Participants with Adverse Events (AEs) According to Common Terminology Criteria for Adverse Events (CTCAE)
Outcome Description
NCI PRO-CTCAE is a patient-reported item library used to evaluate symptomatic treatment-emergent adverse events in participants on cancer clinical trials. The items selected for this study include all NCI PRO-CTCAE gastrointestinal items and urinary items. These items include taste changes, decreased appetite, nausea, vomiting, heartburn, gas, bloating, hiccups, constipation, diarrhea, abdominal pain, fecal incontinence, painful, urination, urinary urgency, urinary frequency, change in usual urine color, and urinary incontinence.
Outcome Time Frame
Up to 8 years
Outcome Measure
Number of Participants with AEs by Severity according to Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE)
Outcome Description
Number of participants with clinical laboratory abnormalities will be reported. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.
Outcome Time Frame
Up to 8 years
Outcome Measure
Number of Participants with Clinical Laboratory Abnormalities
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
Alexander Sankin
Investigator Email
asankin@montefiore.org