Safety and Toxicity Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer (Phase 1a) (ADVANCED-1)
Primary Purpose
Non-muscle Invasive Bladder Cancer
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TARA-002
Sponsored by
About this trial
This is an interventional treatment trial for Non-muscle Invasive Bladder Cancer focused on measuring Non-muscle invasive bladder cancer, bladder cancer, high grade Ta, carcinoma in situ, high-grade NMIBC
Eligibility 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.
Sites / Locations
- USC Norris Cancer Center
- Mayo Clinic
- Tulane Medical Center
- Chesapeake Urology Research Associates
- Mayo Clinic
- New Jersey Urology
- Premier Medical Group of the Hudson Valley
- University of Rochester, Department of Urology
- Carolina Urologic Research Center
- Urology Associates PC
- UT Health San Antonio
- PMSI Republican Clinical Hospital "T. Mosneaga," ARENSIA Exploratory Medicine Phase I UnitRecruiting
- Spitalul Clinic de Nefrologie Carol DavilaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TARA-002
Arm Description
TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin.
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
Full Information
NCT ID
NCT05085977
First Posted
October 7, 2021
Last Updated
September 29, 2023
Sponsor
Protara Therapeutics
1. Study Identification
Unique Protocol Identification Number
NCT05085977
Brief Title
Safety and Toxicity Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer (Phase 1a)
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 10, 2022 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Protara Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-muscle Invasive Bladder Cancer
Keywords
Non-muscle invasive bladder cancer, bladder cancer, high grade Ta, carcinoma in situ, high-grade NMIBC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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)
Allocation
N/A
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
TARA-002
Arm Type
Experimental
Arm Description
TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin.
Intervention Type
Biological
Intervention Name(s)
TARA-002
Intervention Description
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.
Primary Outcome Measure Information:
Title
Phase 1a, Dose Escalation Phase: Incidence of DLT AEs in subjects with HGTa or CIS NMIBC
Description
DLT = dose limiting toxicities; HGTa = high grade Ta; CIS = carcinoma in situ, includes CIS with concomitant Ta
Time Frame
Day 1 to Day 43
Title
Phase 1a, Dose Escalation Phase: MTD and RP2D of TARA-002 in subjects with HGTa or CIS NMIBC
Description
MTD = maximum tolerated dose; RP2D = recommended Phase 2 dose
Time Frame
Day 1 to Day 43
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chief Scientific Operations Officer
Phone
16468440337
Email
clinicaltrials@protaratx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chief Scientific Operations Officer
Organizational Affiliation
Protara Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
USC Norris Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90089
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Tulane Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Chesapeake Urology Research Associates
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
Individual Site Status
Completed
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
New Jersey Urology
City
Mount Laurel
State/Province
New Jersey
ZIP/Postal Code
08054
Country
United States
Individual Site Status
Completed
Facility Name
Premier Medical Group of the Hudson Valley
City
Poughkeepsie
State/Province
New York
ZIP/Postal Code
12603
Country
United States
Individual Site Status
Completed
Facility Name
University of Rochester, Department of Urology
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Carolina Urologic Research Center
City
Myrtle Beach
State/Province
South Carolina
ZIP/Postal Code
29572
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Urology Associates PC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37209
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
UT Health San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
PMSI Republican Clinical Hospital "T. Mosneaga," ARENSIA Exploratory Medicine Phase I Unit
City
Chisinau
Country
Moldova, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Spitalul Clinic de Nefrologie Carol Davila
City
Bucharest
ZIP/Postal Code
10731
Country
Romania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety and Toxicity Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer (Phase 1a)
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