Clinical trial NCT05951179: Safety and Efficacy Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer
Official title: A Phase 2, Open-Label Study to Evaluate the Safety and Anti-Tumor Activity of Intravesical Instillation of TARA-002 in Adults With High-Grade Non-Muscle Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-muscle Invasive Bladder Cancer
Keywords: Non-muscle invasive bladder Cancer
bladder cancer
high grade Ta
high grade NMIBC
carcinoma in situ
Lead sponsor: Protara Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-07-18
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All participants will receive 6 weekly instillations of TARA-002 at the established RP2D (First Treatment Period). Participants who are eligible for reinduction after the First Treatment Period will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Participants confirmed to have a complete response after the First Treatment Period will receive 3 additional weekly doses of TARA-002 instillation as maintenance during the Second Treatment Period. All eligible participants will receive 3 weekly doses of TARA-002 instillation as part of the Third Treatment Period (maintenance) at Months 6, 9, 12, 15, and 18. Following the Third Treatment Period, all participants will continue to the Follow up Period from Month 21 until Month 60.
Primary purpose: TREATMENT

Brief summary: TARA-002-101-Ph2 is an open-label study to investigate the safety and anti-tumor activity of intravesical instillation of TARA-002 in adults 18 years of age or older with high-grade CIS NMIBC (± Ta/T1).

The purpose of this Phase 2 study (TARA-002-101-Ph2) is to further assess the safety and anti-tumor activity of TARA-002 at the RP2D which has been established in the Phase 1a dose finding study (TARA-002-101-Ph1a).

This Phase 2 study includes participants with CIS NMIBC (± Ta/T1) with active disease (defined as disease present at last tumor evaluation prior to signing ICF).

Participants will be enrolled into one of 2 cohorts:

Cohort A:

* Participants with CIS (± Ta/T1) who are BCG naive, or
* Participants with CIS (± Ta/T1) who are BCG exposed and have not received intravesical BCG for at least 24 months prior to the most recent CIS diagnosis

Cohort B:

* Participants with persistent or recurrent CIS (± Ta/T1) who are BCG unresponsive within 12 months of completion of adequate BCG therapy (minimum 5/6 doses induction and 2/3 doses maintenance or 2/6 doses reinduction)


Eligibility criteria: Inclusion Criteria:

* Male or female participants 18 years of age or older at the time of signing informed consent
* Participants who have voluntarily given written informed consent after the nature of the study has been explained according to applicable requirements prior to study entry
* Central histologic confirmation of high-grade non-muscle invasive CIS (± Ta/T1) with active disease
* Participants who are BCG naive, or participants who are BCG exposed and have not received intravesical BCG for at least 24 months prior to the most recent CIS diagnosis (Cohort A). Participants with persistent or recurrent CIS (± Ta/T1) who are BCG unresponsive within 12 months of completion of adequate BCG therapy (Cohort B).

Exclusion Criteria:

* Penicillin allergy (participants with a questionable history of allergy to penicillin will undergo penicillin blood allergy testing via central laboratory
* Predominant (defined as \> 50%) adenocarcinoma, squamous cell carcinoma, or histological variants including plasmacytoid, sarcomatoid, or squamous components according to central review
* Concomitant prostatic or upper tract urothelial involvement per Investigator's assessment
* Nodal and metastatic disease are excluded if they existed at any time (whether present or in the past)
* Any history of ≥ T2 bladder cancer that existed at any point in time in the participant's history

For more information on eligibility criteria, please contact the Sponsor

Primary outcomes:
measure: Cohort A and B: Incidence of high-grade Complete Response at any time according to central pathology after treatment with TARA-002
timeFrame: Month 3 to Month 60
measure: Cohort A: Incidence of high-grade Complete Response at any time by subgroup (BCG naive and BCG exposed > 24 months) according to central pathology after treatment with TARA-002
timeFrame: Month 3 to Month 60
Secondary outcomes:
measure: Cohort A and B: Duration of high-grade Complete Response rate at Months 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 after treatment with TARA-002
timeFrame: Month 3 to Month 60
measure: Cohort A and B: High-grade Complete Response rate at Months 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 after treatment with TARA-002
timeFrame: Month 3 to Month 60
measure: Cohort A and B: Duration of Complete Response (all recurrent bladder cancer, including low grade Ta) after treatment with TARA-002
timeFrame: Month 3 to Month 60
measure: Cohort A and B: Complete Response rate (all recurrent bladder cancer, including low grade Ta) at Months 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 after treatment with TARA-002
timeFrame: Month 3 to Month 60
measure: Cohort A and B: Progression free survival after treatment with TARA-002
timeFrame: 60 months
measure: Cohort A and B: Disease-specific progression free survival after treatment with TARA-002
timeFrame: 60 months
measure: Cohort A and B: Overall survival after treatment with TARA-002
timeFrame: 60 months
measure: Cohort A and B: Disease specific survival after treatment with TARA-002
timeFrame: 60 months
measure: Cohort A and B: Time to cystectomy after treatment with TARA-002
timeFrame: 60 months
measure: Cohort A and B: Time to recurrence delayed cystectomy after treatment with TARA-002
timeFrame: 60 months
measure: Cohort A and B: Time to progression after treatment with TARA-002
timeFrame: 60 months
measure: Cohort A and B: Time to disease worsening after treatment with TARA-002
timeFrame: 60 months
measure: Cohort A and B: Incidence and severity of AEs, TEAEs, SAEs and TESAEs after treatment with TARA-002
timeFrame: Day 1 to Month 60
measure: Cohort A and B: Change from baseline in urine pharmacodynamic biomarker levels (including IL-6, IL-8, IFN-γ, and TNF-α) after treatment with TARA-002
timeFrame: Day 1 to Day 72
measure: Cohort A and B: Quality of Life based on the EORTC questionnaire QLQ-NMIBC24
timeFrame: Day 1 to Month 24
measure: Cohort A and B: Quality of Life based on the EORTC questionnaire QLQ-C30
timeFrame: Day 1 to Month 24
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Los Angeles
country: United States
facility: Urology Group of Southern California
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Aurora
country: United States
facility: Colorado University - Anshutz
state: Colorado
city: Lakewood
country: United States
facility: Advanced Urology
state: Colorado
city: Lone Tree
country: United States
facility: Urology Associates of Denver
state: Colorado
city: Gainesville
country: United States
facility: University of Florida Health Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Lafayette
country: United States
facility: Southern Urology
state: Louisiana
city: Shreveport
country: United States
facility: Ochsner Health LSU - Regional Urology
state: Louisiana
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Garden City
country: United States
facility: AccuMed Research Associates
state: New York
city: Rochester
country: United States
facility: University of Rochester, Department of Urology
state: New York
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Memphis
country: United States
facility: Conrad Person Clinic
state: Tennessee
city: Nashville
country: United States
facility: Urology Associates PC
state: Tennessee
city: Austin
country: United States
facility: Urology Austin, LLC
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Richmond
country: United States
facility: Virginia Urology
state: Virginia
city: Caba
country: Argentina
facility: Hospital Sirio Libanes
city: Cordoba
country: Argentina
facility: Centro Urologico Profesor Bengio SA
city: Abbotsford
country: Canada
facility: Exdeo Clinical Research Inc
state: British Columbia
city: Brampton
country: Canada
facility: Jonathan Giddes Medicine Professional Corporation
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Kapitanivka
country: Ukraine
facility: Arensia Kapitanivka - PPDS
Study officials:
affiliation: Protara Therapeutics
name: Chief Scientific Operations Officer
role: STUDY_DIRECTOR
References: