A Study of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-invasive Bladder Cancer (MIBC) of the Bladder (SunRISe-2)

• ClinicalTrials.gov Identifier: NCT04658862
• Recruitment Status: Recruiting
• First Posted: December 9, 2020
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: November 19, 2020
• First Posted Date: December 9, 2020
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: December 7, 2020
• Estimated Primary Completion Date: December 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 7, 2020)

Time from Randomization to the First Bladder Intact Event-free Survival (BI-EFS) event [ Time Frame: Up to 8 years ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 6, 2023)

• Metastasis-free survival (MFS) [ Time Frame: Up to 8 years ]
  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.
• Overall Survival (OS) [ Time Frame: Up to 8 years ]
  OS is defined as time from randomization to death.
• Overall Response Rate (ORR) [ Time Frame: Up to 8 years ]
  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).
• Number of Participants with Adverse Events (AEs) According to Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 8 years ]
  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.
• Number of Participants with AEs by Severity according to Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE) [ Time Frame: Up to 8 years ]
  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.
• Number of Participants with Clinical Laboratory Abnormalities [ Time Frame: Up to 8 years ]
  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.

Original Secondary Outcome Measures (submitted: December 7, 2020)

• Metastasis-free survival (MFS) [ Time Frame: Up to 8 years ]
  MFS is measured from time from randomization to first radiologic (as assessed by RECIST 1.1 criteria) or histologic evidence of metastatic disease or death due to any cause.
• Overall Survival (OS) [ Time Frame: Up to 8 years ]
  OS is defined as time from randomization to death.
• Overall Response Rate (ORR) [ Time Frame: Up to 8 years ]
  ORR is defined as proportion of participants who have complete response (CR) (defined as Negative biopsy, and Computed tomography/Magnetic resonance imaging [CT/MRI] of chest, abdomen, and pelvis showing no evidence of local recurrence, progression, or metastatic disease) or partial response (PR): (defined as down staging: biopsy proven non-invasive disease less than [<] T1 and CT/MRI of chest, abdomen, and pelvis showing no evidence of metastatic disease) or non-response (those not achieving a complete response or down-staging, or those who do not undergo a biopsy will be considered non-responders).
• Number of Participants with Adverse Events (AEs) According to Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 8 years ]
  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.
• Number of Participants with AEs by Severity according to Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE) [ Time Frame: Up to 8 years ]
  NCI PRO-CTCAE is a patient-reported outcome measure used to evaluate symptomatic toxicity in participants on cancer clinical trials. The NCI PRO-CTCAE is an item bank. 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.
• Number of Participants with Clinical Laboratory Abnormalities [ Time Frame: Up to 8 years ]
  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.
• Change from Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: From Baseline up to 8 years ]
  Change from baseline in systolic and diastolic blood pressure over time will be assessed.
• Change From Baseline in Heart Rate [ Time Frame: From Baseline up to 8 years ]
  Change from baseline in heart rate over time will be assessed.
• Change from Baseline in Temperature [ Time Frame: From Baseline up to 8 years ]
  Change from baseline in temperature over time will be assessed.
• Safety Assessment by Changes From Baseline in Physical Examinations [ Time Frame: From Baseline up to 8 years ]
  Physical examination which will be comprised of an examination of head, ears, eyes, nose, throat and neck, cardiovascular, respiratory, abdomen, musculoskeletal, skin, and genitourinary systems as assessed as normal or abnormal. A change from normal to abnormal or abnormal to normal, will be registered as a change from baseline.
• Change from Baseline in Performance Status as assessed by Eastern Cooperative Oncology Group (ECOG) Scale [ Time Frame: From baseline up to 8 years ]
  Change from baseline in performance status will be assessed by ECOG scale, where Grade 0 (fully active), Grade 1 (restricted in physically strenuous activity), Grade 2 (ambulatory and capable of all self-care), Grade 3 (capable of only limited self-care), Grade 4 (completely disabled), and Grade 5 (dead).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Urinary Bladder Neoplasms

Intervention

• Biological: Cetrelimab
  Participants will receive intravenous Cetrelimab.
  Other Name: JNJ-63723283
• Drug: TAR-200
  Participants will receive intravesical TAR-200.
  Other Name: JNJ-17000139
• Drug: Cisplatin
  Participants will receive cisplatin intravenously.
• Drug: Gemcitabine
  Participants will receive gemcitabine intravenously.
• Radiation: Conventional radiation therapy
  Participants will receive conventional radiation therapy for bladder (64 gy).
• Radiation: Hypo-fractioned radiation therapy
  Participants will receive hypo-fractioned radiation therapy for bladder (55 gy).

Study Arms

• Experimental: TAR-200 + Cetrelimab
  Participants will receive intravesical TAR-200 every 3 weeks (21 days indwelling) for first 18 weeks and thereafter from Week 24 every 12 weeks through study Year 3 in combination with intravenous (IV) Cetrelimab.
  Interventions:

  • Biological: Cetrelimab
  • Drug: TAR-200
• Active Comparator: Chemotherapy (cisplatin or gemcitabine) + Radiation Therapy
  Participants will receive chemotherapy based on investigator's choice from either cisplatin intravenously once weekly for 4 to 6 treatment weeks or gemcitabine intravenously twice weekly for 4 to 6 treatment weeks as Standard of Care (SOC) along with radiation therapy from either conventional radiotherapy (64 Gray [Gy], bladder only) for up to 6.5 treatment weeks or hypo-fractionated radiotherapy (55 Gy, bladder only) for up to 4 weeks.
  Interventions:

  • Drug: Cisplatin
  • Drug: Gemcitabine
  • Radiation: Conventional radiation therapy
  • Radiation: Hypo-fractioned radiation therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 7, 2020): 550
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 26, 2029
• Estimated Primary Completion Date: December 30, 2026 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, India, Italy, Japan, Korea, Republic of, Mexico, Poland, Portugal, Russian Federation, Spain, Taiwan, Turkey, Ukraine, United States
• Removed Location Countries: Israel, Netherlands, South Africa

Administrative Information

• NCT Number: NCT04658862
• Other Study ID Numbers: CR108917; 2020-002620-36 ( EudraCT Number ); 17000139BLC3001 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trials; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024