A Study to Evaluate TAR-210 Versus Intravesical Chemotherapy Treatment in Participants With High Risk Non-Muscle-Invasive Bladder Cancer

Official title

A Phase 3, Randomized, Open-label, Multicenter Study Evaluating the Efficacy and Safety of TAR-210 Erdafitinib Intravesical Delivery System Versus Investigator's Choice of Intravesical Chemotherapy in Participants With High-risk Non-muscle-invasive Bladder Cancer With Susceptible FGFR Alterations Who Had Received Intravesical Bacillus Calmette-Guérin (BCG)

Overview

The main purpose of this study is to compare the disease-free survival (the length of time after randomization that a participant survives without any signs or symptoms of the cancer returning, or progressing) between Bacillus Calmette-Guérin (BCG) treated participants receiving treatment with TAR-210 versus investigator's choice of intravesical chemotherapy for treatment of high-risk non-muscle-invasive bladder cancer (HR-NMIBC).

Interventions

• Drug TAR-210
  TAR-210 will be administered intravesically.
• Drug Mitomycin C
  MMC will be administered intravesically.
• Drug Gemcitabine
  Gemcitabine will be administered intravesically.

Primary outcome measures

• Disease-free Survival (DFS) [Time frame: Up to 5 years]

Secondary outcome measures (12)

• Recurrence-Free Survival (RFS) [Time frame: Up to 5 years]
• Time to Next Intervention (TTNI) [Time frame: Up to 5 years]
• Time to Disease Worsening (TTDW) [Time frame: Up to 5 years]
• Time to Progression (TTP) [Time frame: Up to 5 years]
• Overall Survival (OS) [Time frame: Up to 5 years]
• Number of Participants with Adverse Events (AEs) According to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [Time frame: Up to 5 years]
• Number of Participants With Change from Baseline in Laboratory Abnormalities [Time frame: Up to 5 years]
• Number of Participants With Change from Baseline in Vital Signs Abnormalities [Time frame: Up to 5 years]
• Change from Baseline in European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ)-C30 Scores [Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96]
• Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores [Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96]
• Percentage of Participants With Meaningful Change From Baseline in EORTC-QLQ-C30 Scores [Time frame: Weeks 12, 24, 36, 48, 60, 72, 84 and 96]
• Percentage of Participants With Meaningful Change From Baseline in EORTC-QLQ-NMIBC24 Scores [Time frame: Weeks 12, 24, 36, 48, 60, 72, 84 and 96]

Eligibility criteria

Inclusion criteria

• Histologically confirmed diagnosis by local pathology of papillary-only HR-NMIBC (defined as high-grade Ta or any T1, no CIS). Mixed histology tumors are allowed if urothelial differentiation is predominant. However, neuroendocrine, and small cell variants will be excluded
• Have a susceptible fibroblast growth factor receptor (FGFR) mutation or fusion either by urine testing or tumor tissue testing (from TURBT tissue) as determined by central or local testing
• All visible tumor completely resected prior to randomization. Urine cytology must not be positive or suspicious for high grade UC before randomization. For participants with lamina propria invasion (T1) on the screening biopsy/TURBT, muscularis propria must be present to rule out MIBC
• Participants must have had either: a. Adequate Induction (5 of 6 doses) and either 2 of 3 doses of Maintenance or 2 of 6 doses of second Induction of BCG with high-grade T1 disease at first disease assessment after induction or high-grade Ta/any T1 disease within 6 months after last BCG (BCG-unresponsive population); b. had adequate induction (5 or 6 doses) with or without maintenance BCG with high-grade Ta/any T1 disease within 12 months after last BCG excluding BCG-unresponsive (BCG-experienced population); or c. been unable to complete an induction course of BCG with at least 5 doses due to grade >= 2 toxicity requiring BCG discontinuation (BCG intolerant population)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0, 1, or 2
• Must be ineligible for or refusing radical cystectomy (RC)

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 \[i.e.\], T2, T3, T4, N+, and/or M+)
• Active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. Allowed recent second or prior malignancies: a. Any malignancy that was not progressing nor requiring treatment change in the last 12 months; b. Malignancies treated within the last 12 months and considered at very low risk for recurrence for example (e.g.): non-melanoma skin cancers (treated with curative therapy or localized melanoma treated with curative surgical resection alone), non-invasive cervical cancer, breast cancer (adequately treated lobular CIS or ductal CIS, localized breast cancer and receiving antihormonal agents), localized prostate cancer (\[N0, M0\] with a Gleason score less than or equal to \[<=\] 7a, treated locally only \[radical prostatectomy/radiation therapy/focal treatment\]) and other malignancy that is considered at minimal risk of recurrence
• 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 210
• A history of clinically significant polyuria with recorded 24 hour urine volumes greater than (>) 4,000 milliliters (mL)
• Indwelling catheters are not permitted; however, intermittent catheterization is acceptable

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 25 centers

• Academic Urology and Urogynecology of Arizona — Sun City
• UCLA — Los Angeles
• Colorado Clinical Research — Lakewood
• Advanced Urology Institute — Largo
• Georgia Urology — Atlanta
• Associated Urological Specialists — Chicago Ridge
• Urology of Indiana — Carmel
• Southern Urology LLC — Lafayette
• … and 17 more centers

China · 9 centers

• Peking University First Hospital — Beijing
• The Third People's Hospital of Chengdu — Chengdu
• West China Hospital Sichuan University — Chengdu
• Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University — Guangzhou
• Nanjing Drum Tower Hospital — Nanjing
• The First Affiliated Hospital of Ningbo University — Ningbo
• The Second Hospital Of Tianjin Medical University — Tianjin
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou
• … and 1 more center

Spain · 9 centers

Center list to be confirmed — check the primary protocol.

Italy · 8 centers

• Cliniche Humanitas Gavazzeni — Bergamo
• ASST Spedali Civili Brescia — Brescia
• SPDC Villa Scassi — Genova
• Ospedale San Raffaele — Milan
• Fondazione G Pascale Istituto Nazionale Tumori IRCCS — Naples
• Istituto Nazionale Tumori Regina Elena — Roma
• Aou San Luigi Gonzaga — Sanatorio San Luigi
• … and 1 more center

Japan · 8 centers

Center list to be confirmed — check the primary protocol.

France · 7 centers

• Institut Paoli Calmettes — Marseille
• Hopital Saint Louis — Paris
• CHU Pitie Salpetriere — Paris
• Hopital Saint Joseph — Paris
• Clinique de la Croix du Sud — Quint-Fonsegrives
• CHP Saint Gregoire — Saint-Grégoire
• Gustave Roussy — Villejuif

Germany · 6 centers

• Universitaetsklinikum Koeln — Cologne
• Marien hospital Herne — Herne
• Klinikum Leverkusen gGmbH — Leverkusen
• Universitaetsklinikum Mannheim — Mannheim
• Studienpraxis Urologie Nurtingen — Nürtingen
• Caritas-Krankenhaus St. Josef — Regensburg

Israel · 6 centers

• Rambam Medical Center — Haifa
• Carmel Medical Center — Haifa
• Meir Medical Center — Kfar Saba
• Rabin Medical Center — Petah Tikva
• Sheba Medical Center — Ramat Gan
• Tel Aviv Sourasky Medical Center — Tel Aviv

Argentina · 5 centers

• Hospital Sirio Libanes — Buenos Aires
• Instituto Alexander Fleming — Buenos Aires
• Investigaciones Clinico Moleculares (ICM) — Caba
• Centro Urologico Profesor Bengio — Córdoba
• Sanatorio de la Mujer — Rosario

Belgium · 5 centers

• Hopital Erasme — Brussels
• Ziekenhuis Oost-Limburg — Genk
• AZ Maria Middelares — Ghent
• Universitair Ziekenhuis Leuven — Leuven
• Algemeen Ziekenhuis Delta — Roeselare

Brazil · 5 centers

• Liga Norte Riograndense Contra O Cancer — Natal
• Hospital Regional do Cancer - Hospital de Esperanca — Presidente Prudente
• Fundacao Faculdade Regional De Medicina De Sao Jose Do Rio Preto — São José do Rio Preto
• Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo — São Paulo
• Real e Benemerita Associacao Portuguesa de Beneficencia — São Paulo

Greece · 5 centers

• General Hospital of Athens G Gennimatas — Athens
• Laiko General Hospital of Athens — Athens
• Sismanogleio General Hospital — Athens
• General Hospital Of Thessaloniki Papageorgiou — Thessaloniki
• Athens Medical Center S A Interbalkan Medical Center of Thessaloniki — Thessaloniki

South Korea · 5 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 5 centers

Center list to be confirmed — check the primary protocol.

Netherlands · 4 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06919965 · 42756493BLC3005 · 42756493BLC3005 · 2024-519493-39-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗