Safety and Toxicity Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer (Phase 1a) (ADVANCED-1)

• ClinicalTrials.gov Identifier: NCT05085977
• Recruitment Status: Recruiting
• First Posted: October 20, 2021
• Last Update Posted: May 3, 2024
• Sponsor: Protara Therapeutics
• Information provided by (Responsible Party): Protara Therapeutics

Study Description

Brief Summary:

This study is an open-label dose escalation study (Phase 1a) to investigate the safety and toxicity of intravesical treatment of high-grade NMIBC (HGTa or CIS, including CIS with concomitant Ta) after transurethral resection of bladder tumor (TURBT) and/or biopsy using TARA-002 in adults unable to obtain intravesical Bacillus Calmette-Guérin (BCG), adults who have received at least one dose of intravesical BCG or adults who have received at least one dose of intravesical chemotherapy. Dosing will start in subjects with HGTa or CIS (including CIS with concomitant Ta), and all subjects will receive 6 weeks of treatment at a fixed volume with varying dose levels.

Condition or disease	Intervention/treatment	Phase
Non-muscle Invasive Bladder Cancer	Biological: TARA-002	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: First, up to 3 dose levels of TARA-002 (10 KE → 20 KE → 40 KE) will be tested sequentially with 6 weekly intravesical doses starting with the lowest dose using a 3+3 design in a dose escalation manner until the RP2D has been established. If the MTD is not reached, additional cohorts of dose levels higher than 40 KE may be explored.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1a/b Dose Finding, Open-label Study to Evaluate Safety and Toxicity of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer
• Actual Study Start Date: March 10, 2022
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: July 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Biological: TARA-002; Phase 1a, Dose Escalation: First, up to 3 dose levels of TARA-002 (10 KE → 20 KE → 40 KE) will be tested sequentially with 6 weekly intravesical doses starting with the lowest dose using a 3+3 design in a dose escalation manner until the RP2D has been established. If the MTD is not reached, additional cohorts of dose levels higher than 40 KE may be explored.

Outcome Measures

Primary Outcome Measures :

1. Phase 1a, Dose Escalation Phase: Incidence of DLT AEs in subjects with HGTa or CIS NMIBC [ Time Frame: Day 1 to Day 43 ]
   DLT = dose limiting toxicities; HGTa = high grade Ta; CIS = carcinoma in situ, includes CIS with concomitant Ta
2. Phase 1a, Dose Escalation Phase: MTD and RP2D of TARA-002 in subjects with HGTa or CIS NMIBC [ Time Frame: Day 1 to Day 43 ]
   MTD = maximum tolerated dose; RP2D = recommended Phase 2 dose

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female subjects 18 years of age or older at the time of signing the informed consent
• Subjects who have voluntarily given written informed consent after the nature of the study has been explained according to applicable requirements prior to study entry
• Subjects with a histologically confirmed, high-grade Ta or CIS (including CIS with concomitant Ta) urothelial cell carcinoma of the bladder on central review
• Subjects who are treatment naïve, are unable to obtain intravesical BCG for the treatment of NMIBC, have received at least one dose of intravesical BCG, or at least one dose of intravesical chemotherapy

Exclusion Criteria:

• Penicillin allergy (subjects with a questionable history of allergy to penicillin or no history of penicillin use will undergo penicillin blood allergy testing prior to inclusion in the study)
• 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 involvement or metastatic disease that existed at any time (past or present disease)
• Bladder cancer stage ≥ T1 within the last 36 months according to central histology review
• Bladder cancer stage CIS with concomitant T1

For more information on eligibility criteria, please contact the sponsor.

Contacts and Locations

Contacts

Contact: Chief Scientific Operations Officer; 16468440337; clinicaltrials@protaratx.com

Locations

United States, California

USC Norris Cancer Center; Active, not recruiting

Los Angeles, California, United States, 90089

United States, Florida

Mayo Clinic; Active, not recruiting

Jacksonville, Florida, United States, 32224

United States, Louisiana

Tulane Medical Center; Active, not recruiting

New Orleans, Louisiana, United States, 70112

United States, Maryland

Chesapeake Urology Research Associates; Completed

Baltimore, Maryland, United States, 21204

United States, Minnesota

Mayo Clinic; Active, not recruiting

Rochester, Minnesota, United States, 55905

United States, New Jersey

New Jersey Urology; Completed

Mount Laurel, New Jersey, United States, 08054

United States, New York

Premier Medical Group of the Hudson Valley; Completed

Poughkeepsie, New York, United States, 12603

University of Rochester, Department of Urology; Active, not recruiting

Rochester, New York, United States, 14642

United States, South Carolina

Carolina Urologic Research Center; Active, not recruiting

Myrtle Beach, South Carolina, United States, 29572

United States, Tennessee

Urology Associates PC; Active, not recruiting

Nashville, Tennessee, United States, 37209

United States, Texas

UT Health San Antonio; Active, not recruiting

San Antonio, Texas, United States, 78229

Moldova, Republic of

PMSI Republican Clinical Hospital "T. Mosneaga," ARENSIA Exploratory Medicine Phase I Unit; Recruiting

Chisinau, Moldova, Republic of

Contact: Use Central Contact

Romania

Spitalul Clinic de Nefrologie Carol Davila; Active, not recruiting

Bucharest, Romania, 10731

Ukraine

Arensia Kapitanivka; Recruiting

Kapitanivka, Ukraine, 08111

Contact: Use Central Contact

Sponsors and Collaborators

Protara Therapeutics

Investigators

• Study Director: Chief Scientific Operations Officer; Protara Therapeutics

More Information

• Responsible Party: Protara Therapeutics
• ClinicalTrials.gov Identifier: NCT05085977
• Other Study ID Numbers: TARA-002-101 (Phase 1a)
• First Posted: October 20, 2021
• Last Update Posted: May 3, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Protara Therapeutics:

Non-muscle invasive bladder cancer; bladder cancer; high grade Ta; carcinoma in situ; high-grade NMIBC

Additional relevant MeSH terms:

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type