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

Non-muscle Invasive Bladder Cancer Clinical Trial

— ADVANCED-1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05085977
• Other study ID #: TARA-002-101 (Phase 1a)
• Status: Recruiting
• Phase: Phase 1
• Start date: March 10, 2022
• Est. completion date: July 2024

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: July 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Non-muscle Invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Moldova, Republic of	PMSI Republican Clinical Hospital "T. Mosneaga," ARENSIA Exploratory Medicine Phase I Unit	Chisinau
Romania	Spitalul Clinic de Nefrologie Carol Davila	Bucharest
Ukraine	Arensia Kapitanivka	Kapitanivka
United States	Chesapeake Urology Research Associates	Baltimore	Maryland
United States	Mayo Clinic	Jacksonville	Florida
United States	USC Norris Cancer Center	Los Angeles	California
United States	New Jersey Urology	Mount Laurel	New Jersey
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Urology Associates PC	Nashville	Tennessee
United States	Tulane Medical Center	New Orleans	Louisiana
United States	Premier Medical Group of the Hudson Valley	Poughkeepsie	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester, Department of Urology	Rochester	New York
United States	UT Health San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Protara Therapeutics

Countries where clinical trial is conducted

United States,  Moldova, Republic of,  Romania,  Ukraine, 

Outcome

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