A Study of TAR-200 Versus Intravesical Chemotherapy in Participants With Recurrent High-Risk Non-Muscle-Invasive Bladder Cancer (HR-NMIBC) After Bacillus Calmette-Guérin (BCG)

Phase 3

Recruiting

• Conditions: Non-Muscle Invasive Bladder Neoplasms
• Interventions: Drug: TAR-200; Drug: Mitomycin C; Drug: Gemcitabine

• Registration Number: NCT06211764
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

The purpose of this study is to compare disease free survival (DFS) in participants with recurrence of papillary-only high-risk non-muscle-invasive bladder cancer (HR-NMIBC) within 1 year of last dose of Bacillus Calmette-Guérin (BCG) therapy and who refused or are unfit for Radical Cystectomy (RC), receiving TAR-200 versus investigator's choice of single agent intravesical chemotherapy.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-01-09
• Study First Submitted QC: 2024-01-09
• Study First Posted: 2024-01-18
• Study Start: 2024-04-09
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-09
• Last Update Posted: 2025-01-10
• Primary Completion: 2030-11-27
• Study Completion: 2031-04-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

• Histologically confirmed diagnosis by local pathology (within 90 days of documented informed consent) of recurrent, papillary-only high-risk non-muscle-invasive bladder cancer (HR-NMIBC) [defined as high-grade Ta or any T1, no carcinoma in situ (CIS)]
• Participants with variant histologic subtypes are allowed if tumor(s) demonstrate urothelial (transitional cell histology) predominance. However, neuroendocrine, and small cell variants will be excluded
• Participants must be ineligible for or have elected not to undergo Radical Cystectomy (RC)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0, 1, or 2

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Exclusion Criteria

• Presence of CIS at any point from time of diagnosis of papillary-only HR-NMIBC recurrence to randomization. Additionally, presence or history of histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (that is, T2, T3, T4, N+, and/or M+)
• 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. Participants with tumors involving the prostatic urethra in men will be excluded
• A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4000 milliliters (>4000 mL)
• Indwelling catheters are not permitted; however, intermittent catheterization is acceptable
• Previous treatment with TAR-200

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A: TAR-200	TAR-200	Participants will receive intravesical TAR-200 every 3 weeks during an induction phase and every 12 weeks during a maintenance phase.
Group B: Mitomycin C (MMC) or Gemcitabine	Mitomycin C	Participants will receive either single agent intravesical MMC or gemcitabine every week during an induction phase and every 4 weeks during a maintenance phase.
Group B: Mitomycin C (MMC) or Gemcitabine	Gemcitabine	Participants will receive either single agent intravesical MMC or gemcitabine every week during an induction phase and every 4 weeks during a maintenance phase.

Primary Outcome Measures

Name	Time	Method
Disease-free Survival (DFS)	Up to 6 years 7 months	DFS will be measured as the time from randomization to the time of the first recurrence of high-risk non-muscle-invasive bladder cancer (HR-NMIBC) \[high grade (HG) Ta, any T1 or carcinoma in situ (CIS)\], progression, or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Recurrence-Free Survival (RFS)	Up to 6 years 7 months	RFS will be measured as the time from randomization to the time of the first recurrence of HR-NMIBC (HG Ta, any T1 or CIS), or death due to any cause, whichever occurs first.
Time to Next Intervention (TTNI)	Up to 6 years 7 months	TTNI will be measured as the time from randomization to the time of next intervention (localized or systemic) for the treatment of bladder cancer.
Time to Disease Worsening (TTDW)	Up to 6 years 7 months	TTDW is measured as the time from randomization to cystectomy, systemic therapy, or radiation therapy (treatments of disease worsening).
Time to Progression (TTP)	Up to 6 years 7 months	TTP will be measured as the time from randomization to the time of first documented evidence of disease progression (that is, progression to muscle-invasive bladder cancer \[MIBC\] \[T greater than or equal to {\>=} 2\], lymph node \[N+\], or distant disease \[M+\]), or death due to disease progression, whichever occurs first.
Overall Survival (OS)	Up to 6 years 7 months	OS is defined as the time from randomization to death, due to any cause.
DFS Rate at 12 and 24 Months	At 12 and 24 months	DFS rate that is percentage of participants with DFS at 12 and 24 months will be reported.
Number of Participants with Adverse Events (AEs) According to Common Terminology Criteria for Adverse Events (CTCAE)	Up to 6 years 7 months	Number of participants with AEs by severity grade as assessed by CTCAE version 5 will be reported. Grade refers to the severity of AE as follows: Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5- Death related to adverse event.
Number of Participants With Change from Baseline in Laboratory Abnormalities	Up to 6 years 7 months	Number of participants with change from baseline in laboratory abnormalities (including hematology, clinical chemistry and routine urinalysis) will be reported.
Number of Participants With Change from Baseline in Vital Signs Abnormalities	Up to 6 years 7 months	Number of participants with change from baseline in vital signs including temperature, pulse/heart rate, respiratory rate, and blood pressure (systolic and diastolic) (supine) will be reported.
Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) - C30 Scores	Up to 5 years	EORTC QLQ-C30 is a 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. It includes 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea or vomiting), and a global health status or HRQoL scale. Ratings for each item range from 1 (not at all) to 4 (very much).
Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores	Up to 5 years	EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with NMIBC. The questionnaire is designed to supplement the QLQ-C30 and incorporates 6 multi-item scales (urinary symptoms, malaise, future worries, bloating and flatulence, sexual function and male sexual problems) and 5 single items (intravesical treatment issues, sexual intimacy, worries about risk of contaminating partner, sexual enjoyment, and female sexual problems). Ratings for each item range from 1 (not at all) to 4 (very much).
Proportion of Participants With Meaningful Change in EORTC QLQ-C30 and EORTC QLQ-NMIBC24 Scores	Up to 5 years	Proportion of participants with meaningful change in EORTC QLQ-C30 and EORTC QLQ-NMIBC24 scores will be reported.

Trial Locations

Locations (114)

Low Country Urology Clinics; 🇺🇸 North Charleston, South Carolina, United States

Houston Metro Urology; 🇺🇸 Houston, Texas, United States

The Urology Group; 🇺🇸 Cincinnati, Ohio, United States

Wichita Urology Group; 🇺🇸 Wichita, Kansas, United States

Centro Urologico Profesor Bengio; 🇦🇷 Córdoba, Argentina

Algemeen ziekenhuis Maria Middelares; 🇧🇪 Gent, Belgium

Toho University Sakura Medical Center; 🇯🇵 Sakura, Japan

Carolina Urologic Research Center; 🇺🇸 Myrtle Beach, South Carolina, United States

Cliniques Universitaires Saint Luc; 🇧🇪 Bruxelles, Belgium

Ziekenhuis Oost-Limburg; 🇧🇪 Genk, Belgium

National Hospital Organization Okayama Medical Center; 🇯🇵 Okayama, Japan

Wojewodzki Szpital im Sw Ojca Pio w Przemyslu; 🇵🇱 Przemysl, Poland

AZ Sint-Jan; 🇧🇪 Brugge, Belgium

IN VIVO Sp. z o.o; 🇵🇱 Bydgoszcz, Poland

Centrul Medical Unirea SRL; 🇷🇴 Brasov, Romania

Investigaciones Clinico Moleculares (ICM); 🇦🇷 Caba, Argentina

Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica; 🇦🇷 Cordoba, Argentina

Toranomon Hospital; 🇯🇵 Tokyo, Japan

Spitalul Clinic Judetean de Urgenta Pius Brinzeu; 🇷🇴 Timisoara, Romania

National Cancer Center; 🇰🇷 Gyeonggi-do, Korea, Republic of

Funabashi Munitiple Medical Center; 🇯🇵 Chiba, Japan

Uniwersytecki Szpital Kliniczny w Bialymstoku; 🇵🇱 Bialystok, Poland

Yokohama City University Medical Center; 🇯🇵 Yokohama, Japan

Institutul Oncologic Ion Chiricuta; 🇷🇴 Cluj-Napoca, Romania

Istituto Clinico Humanitas; 🇮🇹 Rozzano, Italy

Urology Associates; 🇺🇸 Nashville, Tennessee, United States

Florida Urology Partners; 🇺🇸 Riverview, Florida, United States

UroPartners; 🇺🇸 Chicago Ridge, Illinois, United States

Specialty Clinical Research of St Louis; 🇺🇸 Saint Louis, Missouri, United States

Urology of Indiana; 🇺🇸 Carmel, Indiana, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Comprehensive Urology; 🇺🇸 Royal Oak, Michigan, United States

Central Ohio Urology Group; 🇺🇸 Gahanna, Ohio, United States

Associated Medical Professionals; 🇺🇸 Syracuse, New York, United States

Centers for Advanced Urology LLC d b a MidLantic Urology; 🇺🇸 Bala-Cynwyd, Pennsylvania, United States

Urology Austin; 🇺🇸 Austin, Texas, United States

Urology Clinics of North Texas; 🇺🇸 Dallas, Texas, United States

Clinica Santa Isabel; 🇦🇷 Buenos Aires, Argentina

Hospital Privado de la Comunidad; 🇦🇷 Mar del Plata, Argentina

Liga Paranaense de Combate ao Cancer; 🇧🇷 Curitiba, Brazil

Fundacao Pio XII; 🇧🇷 Barretos, Brazil

NAIC Nair Antunes Instituto do Cancer; 🇧🇷 Bauru, Brazil

Irmandade Santa Casa de Misericordia de Porto Alegre; 🇧🇷 Porto Alegre, Brazil

Fundacao Antonio Prudente A C Camargo Cancer Center; 🇧🇷 Sao Paulo, Brazil

West China School of Medicine/West China Hospital, Sichuan University; 🇨🇳 Cheng Du Shi, China

Chongqing Cancer Hospital; 🇨🇳 Chong Qing, China

Shengjing Hospital Of China Medical University; 🇨🇳 Shen Yang Shi, China

The Second Hospital Of Tianjin Medical University; 🇨🇳 Tianjin, China

Tongji Medical College of Huazhong University Science Technology of Medicine Health Management; 🇨🇳 Wuhan, China

Xi an Jiaotong University Hospital; 🇨🇳 XI An Shi, China

Polyclinique de Limoges - Francois Chenieux; 🇫🇷 Limoges, France

Hopital Claude Huriez; 🇫🇷 Lille, France

Institut Paoli Calmettes; 🇫🇷 Marseille, France

Clinique de la Croix du Sud; 🇫🇷 Quint-Fonsegrives, France

Hopital Foch; 🇫🇷 Suresnes, France

APHP - Hopital Bichat - Claude Bernard; 🇫🇷 Paris, France

Universitaetsklinikum Koeln; 🇩🇪 Köln, Germany

Klinikum Leverkusen gGmbH; 🇩🇪 Leverkusen, Germany

Universitatsklinikum Schleswig Holstein Campus Lubeck; 🇩🇪 Lubeck, Germany

Ospedale San Donato; 🇮🇹 Arezzo, Italy

PO Molinette Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino; 🇮🇹 Torino, Italy

Hakodate Goryoukaku Hospital; 🇯🇵 Hakodate, Japan

Niigata Cancer Center Hospital; 🇯🇵 Niigata, Japan

Szpital Wojewodzki im. Sw. Lukasza SP ZOZ; 🇵🇱 Tarnow, Poland

Mazowiecki Szpital Onkologiczny; 🇵🇱 Wieliszew, Poland

MICS Centrum Medyczne Torun; 🇵🇱 Torun, Poland

Ponderas Academic Hospital; 🇷🇴 Bucuresti, Romania

Regina Maria; 🇷🇴 Cluj-Napoca, Romania

Hosp. Gral. Univ. Gregorio Maranon; 🇪🇸 Madrid, Spain

Hosp. Univ. 12 de Octubre; 🇪🇸 Madrid, Spain

Hosp Virgen de La Victoria; 🇪🇸 Málaga, Spain

Spokane Urology; 🇺🇸 Spokane, Washington, United States

First Urology, PSC; 🇺🇸 Jeffersonville, Indiana, United States

Genesis Research LLC; 🇺🇸 Torrance, California, United States

Arkansas Urology; 🇺🇸 Little Rock, Arkansas, United States

University of California Irvine Medical Center; 🇺🇸 Orange, California, United States

Colorado Clinical Research; 🇺🇸 Lakewood, Colorado, United States

Algemeen Ziekenhuis Delta; 🇧🇪 Roeselare, Belgium

Sun Yat-Sen University Cancer Center; 🇨🇳 Guang Zhou Shi, China

Peking University First Hospital; 🇨🇳 Beijing, China

Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, China

Real e Benemérita Associação Portuguesa de Beneficência; 🇧🇷 Sao Paulo, Brazil

The First Affiliated Hospital of Wenzhou Medical University; 🇨🇳 Wenzhou, China

Universitaetsklinikum Halle Saale; 🇩🇪 Halle (Saale), Germany

Urologie Neandertal Praxis Mettmann; 🇩🇪 Mettmann, Germany

Klinikum der Universitaet Muenchen; 🇩🇪 Munchen, Germany

Ospedale Provinciale di Macerata; 🇮🇹 Macerata, Italy

Ospedale S. Maria Delle Croci; 🇮🇹 Ravenna, Italy

Hyogo Prefectural Amagasaki General Medical Center; 🇯🇵 Hyogo, Japan

Universita Campus Bio-Medico di Roma; 🇮🇹 Roma, Italy

Istituto Nazionale Tumori Regina Elena; 🇮🇹 Roma, Italy

Chungbuk National University Hospital; 🇰🇷 Chungcheongbuk Do, Korea, Republic of

Keimyung University Dongsan Hospital; 🇰🇷 Daegu, Korea, Republic of

Chonnam National University Hwasun Hospital; 🇰🇷 Jeollanam-do, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Pusan National University Yangsan Hospital; 🇰🇷 Yangsan-si, Korea, Republic of

The Catholic University of Korea Seoul St Mary s Hospital; 🇰🇷 Seoul, Korea, Republic of

Dolnoslaskie Centrum Onkologii; 🇵🇱 Wroclaw, Poland

Hosp.Univ.Parc Tauli; 🇪🇸 Sabadell, Spain

Salford Royal Hospital; 🇬🇧 Salford, United Kingdom

Hosp. Clinico Univ. de Valencia; 🇪🇸 Valencia, Spain

Hosp. Univ. Marques de Valdecilla; 🇪🇸 Santander, Spain

St Bartholomews Hospital; 🇬🇧 London, United Kingdom

Southampton University Hospital; 🇬🇧 Southampton, United Kingdom

Lister Hospital; 🇬🇧 Stevenage, United Kingdom

USC Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Hospital das Clinicas da Universidade Estadual de Campinas UNICAMP; 🇧🇷 Campinas, Brazil

Hospital da Bahia; 🇧🇷 Salvador, Brazil

Sociedade Beneficente de Senhoras - Hospital Sírio Libanês; 🇧🇷 São Paulo, Brazil

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Ralph H. Johnson Veterans Affairs Medical Center; 🇺🇸 Charleston, South Carolina, United States