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

Phase 2

Recruiting

• Conditions: Non-muscle Invasive Bladder Cancer
• Interventions: Biological: TARA-002

• Registration Number: NCT05951179
• Lead Sponsor: Protara Therapeutics

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-06-29
• Study First Submitted QC: 2023-07-14
• Study First Posted: 2023-07-18
• Study Start: 2023-09-15
• Status Verified: 2024-05
• Last Update Submitted: 2024-11-03
• Last Update Posted: 2024-11-05
• Primary Completion: 2030-05
• Study Completion: 2030-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 127

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).

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TARA-002	TARA-002	TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin.

Primary Outcome Measures

Name	Time	Method
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
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 Outcome Measures

Name	Time	Method
Cohort A and B: Time to cystectomy after treatment with TARA-002	60 months
Cohort A and B: Time to disease worsening after treatment with TARA-002	60 months
Cohort A and B: Disease-specific progression free survival after treatment with TARA-002	60 months
Cohort A and B: Disease specific survival after treatment with TARA-002	60 months
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
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
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
Cohort A and B: Time to recurrence delayed cystectomy after treatment with TARA-002	60 months
Cohort A and B: Time to progression after treatment with TARA-002	60 months
Cohort A and B: Quality of Life based on the EORTC questionnaire QLQ-NMIBC24	Day 1 to Month 24	EORTC = European Organization for Research and Treatment of Cancer; QLQ-NMIBC24 = Questionnaire for Patients with NMIBC
Cohort A and B: Overall survival after treatment with TARA-002	60 months
Cohort A and B: Incidence and severity of AEs, TEAEs, SAEs and TESAEs after treatment with TARA-002	Day 1 to Month 60	AE = adverse event; TEAE = treatment emergent adverse event; SAE = serious adverse event; TESAE = treatment emergent serious adverse event
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
Cohort A and B: Progression free survival after treatment with TARA-002	60 months
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	Day 1 to Day 72
Cohort A and B: Quality of Life based on the EORTC questionnaire QLQ-C30	Day 1 to Month 24	EORTC = European Organization for Research and Treatment of Cancer; QLQ-C30 = Questionnaire for Patients with Cancer

Trial Locations

Locations (16)

Urology Associates of Denver; 🇺🇸 Lone Tree, Colorado, United States

Southern Urology; 🇺🇸 Lafayette, Louisiana, United States

Conrad Person Clinic; 🇺🇸 Memphis, Tennessee, United States

Urology Group of Southern California; 🇺🇸 Los Angeles, California, United States

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

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

AccuMed Research Associates; 🇺🇸 Garden City, New York, United States

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

University of Rochester, Department of Urology; 🇺🇸 Rochester, New York, United States

Urology Associates PC; 🇺🇸 Nashville, Tennessee, United States

Urology Austin, LLC; 🇺🇸 Austin, Texas, United States

Clinical Trial Network; 🇺🇸 Houston, Texas, United States

Virginia Urology; 🇺🇸 Richmond, Virginia, United States

Exdeo Clinical Research Inc; 🇨🇦 Abbotsford, British Columbia, Canada

Jonathan Giddes Medicine Professional Corporation; 🇨🇦 Brampton, Ontario, Canada

Arensia Kapitanivka - PPDS; 🇺🇦 Kapitanivka, Ukraine