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

Phase 3RecruitingNCT06919965

Janssen Research & Development, LLC220 enrolled

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

220

Conditions

Non-Muscle Invasive Bladder Neoplasms

Interventions

TAR-210DRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (113)

Academic Urology and Urogynecology of Arizona

Sun City, Arizona, United States

RECRUITING

UCLA

Los Angeles, California, United States

RECRUITING

Colorado Clinical Research

Lakewood, Colorado, United States

RECRUITING

Advanced Urology Institute

Largo, Florida, United States

Outcomes

Primary Outcomes

Disease-free Survival (DFS)

DFS is measured as the time from randomization to the date of the first recurrence of HR-NMIBC (high-grade Ta, any T1 or carcinoma in situ \[CIS\]), progression, or death due to any cause, whichever occurs first.

Time frame: Up to 5 years

Secondary Outcomes

Recurrence-Free Survival (RFS)

RFS is measured as the time from randomization to the date of the first recurrence of HR-NMIBC (high-grade Ta, any T1, or CIS), or death due to any cause, whichever occurs first.

Time frame: Up to 5 years

Time to Next Intervention (TTNI)

TTNI (i.e., transurethral resection of bladder tumor \[TURBT\], radical cystectomy \[RC\], radiation therapy \[RT\], or chemotherapy) is measured as the time from randomization to the date of next intervention (localized or systemic) for the treatment of urothelial carcinoma (UC).

Time frame: Up to 5 years

Time to Disease Worsening (TTDW)

TTDW is measured as the time from randomization to the date of cystectomy, systemic therapy, or radiation therapy, whichever occurs first.

Time frame: Up to 5 years

Time to Progression (TTP)

TTP is measured as the time from randomization to the date of first documented evidence of disease progression (i.e., 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.

Time frame: Up to 5 years

Overall Survival (OS)

OS is defined as the time from randomization to death due to any cause.

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

Number of participants with AEs by severity grade as assessed by CTCAE version 5.0 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.

Time frame: Up to 5 years

Number of Participants With Change from Baseline in Laboratory Abnormalities

Number of participants with change from baseline in laboratory abnormalities (hematology, serum chemistry and urine analysis) will be reported.

Time frame: Up to 5 years

Number of Participants With Change from Baseline in Vital Signs Abnormalities

Number of participants with change from baseline in vital signs (temperature, pulse/heart rate, respiratory rate and blood pressure) will be reported.

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

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), a global health status or HRQoL scale and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Ratings for each item range from 1 (not at all) to 4 (very much). Higher scores indicate greater functioning, better global health status, or more severe symptoms.

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

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). Higher scores represent a high level of symptoms or problems, except for sexual function and sexual enjoyment, where a higher score represents a higher level of functioning.

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

Number of Participants with Overall Side Effects Measured by EORTC Question 168 (Q168)

EORTC Q168 is a single item from the EORTC item library used to measure the overall impact of treatment side effects. Responses are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." Higher score indicates greater impact.

Time frame: Up to Week 96

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

Overview

Conditions

Interventions

Eligibility

Locations (113)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts