Safety and Efficacy Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer

Non-muscle Invasive Bladder Cancer Clinical Trial

— ADVANCED-2  

Official title:

A Phase 2, Open-Label Study to Evaluate Safety and Anti-Tumor Activity, of Intravesical Instillation of TARA-002 in Adults With High-Grade Non-Muscle Invasive Bladder Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05951179
• Other study ID #: TARA-002-101-Ph2
• Status: Recruiting
• Phase: Phase 2
• Start date: September 15, 2023
• Est. completion date: August 2030

Study information

• Verified date: May 2024
• Source: Protara Therapeutics
• Contact: Chief Scientific Operations Officer
• Phone: 16468440337
• Email: clinicaltrials[@]protaratx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 127
• Est. completion date: August 2030
• Est. primary completion date: May 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Non-muscle Invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Biological:
• TARA-002
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.

Locations

Country	Name	City	State
Ukraine	Arensia Kapitanivka - PPDS	Kapitanivka
United States	Urology Austin, LLC	Austin	Texas
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	AccuMed Research Associates	Garden City	New York
United States	Clinical Trial Network	Houston	Texas
United States	Urology Group of Southern California	Los Angeles	California
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Urology Associates PC	Nashville	Tennessee
United States	Virginia Urology	Richmond	Virginia
United States	University of Rochester, Department of Urology	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
Protara Therapeutics

Countries where clinical trial is conducted

United States,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort A and B: Incidence of high-grade Complete Response at any time according to central pathology after treatment with TARA-002		Month 3 to Month 60
Primary	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		Month 3 to Month 60
Secondary	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		Month 3 to Month 60
Secondary	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		Month 3 to Month 60
Secondary	Cohort A and B: Duration of Complete Response (all recurrent bladder cancer, including low grade Ta) after treatment with TARA-002		Month 3 to Month 60
Secondary	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		Month 3 to Month 60
Secondary	Cohort A and B: Progression free survival after treatment with TARA-002		60 months
Secondary	Cohort A and B: Disease-specific progression free survival after treatment with TARA-002		60 months
Secondary	Cohort A and B: Overall survival after treatment with TARA-002		60 months
Secondary	Cohort A and B: Disease specific survival after treatment with TARA-002		60 months
Secondary	Cohort A and B: Time to cystectomy after treatment with TARA-002		60 months
Secondary	Cohort A and B: Time to recurrence delayed cystectomy after treatment with TARA-002		60 months
Secondary	Cohort A and B: Time to progression after treatment with TARA-002		60 months
Secondary	Cohort A and B: Time to disease worsening after treatment with TARA-002		60 months
Secondary	Cohort A and B: Incidence and severity of AEs, TEAEs, SAEs and TESAEs after treatment with TARA-002	AE = adverse event; TEAE = treatment emergent adverse event; SAE = serious adverse event; TESAE = treatment emergent serious adverse event	Day 1 to Month 60
Secondary	Cohort A and B: Change from baseline in urine pharmacodynamic biomarker levels (including IL-6, IL-8, IFN-?, and TNF-a) after treatment with TARA-002		Day 1 to Day 72
Secondary	Cohort A and B: Quality of Life based on the EORTC questionnaire QLQ-NMIBC24	EORTC = European Organization for Research and Treatment of Cancer; QLQ-NMIBC24 = Questionnaire for Patients with NMIBC	Day 1 to Month 24
Secondary	Cohort A and B: Quality of Life based on the EORTC questionnaire QLQ-C30	EORTC = European Organization for Research and Treatment of Cancer; QLQ-C30 = Questionnaire for Patients with Cancer	Day 1 to Month 24