Back to resultsDose Expansion, Safety and Efficacy Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer (ADVANCED-2)
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, high grade NMIBC, carcinoma in situ
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 Central histologic confirmation of high-grade non-muscle invasive CIS (± Ta/T1) with active disease Subjects who are unable to obtain intravesical BCG, have not received intravesical BCG for 24 months prior to CIS diagnosis, or have persistent or recurrent CIS (± Ta/T1) within 12 months of completion of adequate BCG Exclusion Criteria: Penicillin allergy (subjects 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 subject's history For more information on eligibility criteria, please contact the Sponsor
Sites / Locations
- AccuMed Research AssociatesRecruiting
- Carolina Urologic Research CenterRecruiting
- Urology Associates PCRecruiting
- Virginia UrologyRecruiting
- Arensia Kapitanivka - PPDSRecruiting
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
Cohort A: Incidence of high-grade Complete Response at any time after treatment with TARA-002
Cohort A: Incidence of high-grade Complete Response at any time by subgroup (BCG naive and BCG exposed > 24 months) after treatment with TARA-002
Cohort B: Incidence of high-grade Complete Response at any time after treatment with TARA-002
Secondary Outcome Measures
Cohort A: 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
Cohort A: Change from baseline in inflammatory urine cytokines levels (including IL-6, IL-8, IFN-γ, and TNF-α) after treatment with TARA-002
Cohort A: 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
Cohort A: 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
Cohort B: Duration of high-grade Complete Response after treatment with TARA-002
Cohort B: High-grade Complete Response rate at Months 3, 6, 9, 12, 15, 18, 21, and 24 after treatment with TARA-002
Cohort B: Duration of Complete Response (all recurrent bladder cancer, including low grade Ta) after treatment with TARA-002
Cohort B: Complete Response rate (all recurrent bladder cancer, including low grade Ta) at Months 3, 6, 9, 12, 15, 18, 21, and 24 after treatment with TARA-002
Cohort B: Progression free survival after treatment with TARA-002
Cohort B: Disease-specific progression free survival after treatment with TARA-002
Cohort B: Overall survival after treatment with TARA-002
Cohort B: Disease specific survival after treatment with TARA-002
Cohort B: Time to cystectomy after treatment with TARA-002
Cohort B: Time to recurrence delayed cystectomy after treatment with TARA-002
Cohort B: Time to progression after treatment with TARA-002
Cohort B: Time to disease worsening after treatment with TARA-002
Cohort B: Incidence and severity of AEs, TEAEs, SAEs and TESAEs after treatment with TARA-002
Cohort B: Change from baseline in inflammatory urine cytokines levels (including IL-6, IL-8, IFN-γ, and TNF-α) after treatment with TARA-002
Cohort 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
Cohort 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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05951179
Brief Title
Dose Expansion, Safety and Efficacy Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer
Acronym
ADVANCED-2
Official Title
A Phase 1b/2, Dose Expansion, 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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 15, 2023 (Actual)
Primary Completion Date
August 2026 (Anticipated)
Study Completion Date
August 2026 (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
Yes
5. Study Description
Brief Summary
TARA-002-101-Ph1b/2 is an open-label Phase 1b/2 dose expansion study to investigate the safety and anti-tumor activity of intravesical treatment of high-grade CIS NMIBC (± Ta/T1) with intravesical instillation of TARA-002 in adults 18 years of age or older.
The Phase 1b/2 study (TARA-002-101-Ph1b/2) will be initiated after the RP2D has been established in the Phase 1a dose finding study (TARA-002-101-Ph1a).
This Phase 1b/2 (TARA-002-101-Ph1b/2) dose expansion 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 unable to obtain intravesical BCG, or
Participants with CIS (± Ta/T1) who have not received intravesical BCG for 24 months prior to CIS diagnosis
Cohort B:
Participants with CIS (± Ta/T1) who are BCG unresponsive after completion of adequate BCG therapy (minimum 5/6 doses induction and 2/3 doses maintenance or 2/6 doses reinduction)
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, high grade NMIBC, carcinoma in situ
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Cohort A: All participants will receive 6 weekly instillations of TARA-002 at the established recommended Phase 2 dose (RP2D). Participants who are eligible for reinduction will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period.
Cohort B: All participants will receive 6 weekly instillations of TARA-002 at the established RP2D. Participants who are eligible for reinduction will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Participants confirmed to have a complete response will receive 3 additional weekly doses of TARA-002 instillation as part of 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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
102 (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
Cohort A: All subjects will receive 6 weekly instillations of TARA-002 at the established recommended Phase 2 dose (RP2D). Subjects who are eligible for reinduction will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period.
Cohort B: All subjects will receive 6 weekly instillations of TARA-002 at the established RP2D. Subjects who are eligible for reinduction will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Subjects confirmed to have a complete response will receive 3 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. All eligible subjects 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.
Primary Outcome Measure Information:
Title
Cohort A: Incidence of high-grade Complete Response at any time after treatment with TARA-002
Time Frame
Month 3 to Month 6
Title
Cohort A: Incidence of high-grade Complete Response at any time by subgroup (BCG naive and BCG exposed > 24 months) after treatment with TARA-002
Time Frame
Month 3 to Month 6
Title
Cohort B: Incidence of high-grade Complete Response at any time after treatment with TARA-002
Time Frame
Month 3 to Month 24
Secondary Outcome Measure Information:
Title
Cohort A: Incidence and severity of AEs, TEAEs, SAEs and TESAEs after treatment with TARA-002
Description
AE = adverse event; TEAE = treatment emergent adverse event; SAE = serious adverse event; TESAE = treatment emergent serious adverse event
Time Frame
Day 1 to Month 6
Title
Cohort A: Change from baseline in inflammatory urine cytokines levels (including IL-6, IL-8, IFN-γ, and TNF-α) after treatment with TARA-002
Time Frame
Day 1 to Month 6
Title
Cohort A: Quality of Life based on the EORTC questionnaire QLQ-NMIBC24
Description
EORTC = European Organization for Research and Treatment of Cancer; QLQ-NMIBC24 = Questionnaire for Patients with NMIBC
Time Frame
Day 1 to Month 6
Title
Cohort A: Quality of Life based on the EORTC questionnaire QLQ-C30
Description
EORTC = European Organization for Research and Treatment of Cancer; QLQ-C30 = Questionnaire for Patients with Cancer
Time Frame
Day 1 to Month 6
Title
Cohort B: Duration of high-grade Complete Response after treatment with TARA-002
Time Frame
Month 3 to Month 24
Title
Cohort B: High-grade Complete Response rate at Months 3, 6, 9, 12, 15, 18, 21, and 24 after treatment with TARA-002
Time Frame
Month 3 to Month 24
Title
Cohort B: Duration of Complete Response (all recurrent bladder cancer, including low grade Ta) after treatment with TARA-002
Time Frame
Month 3 to Month 24
Title
Cohort B: Complete Response rate (all recurrent bladder cancer, including low grade Ta) at Months 3, 6, 9, 12, 15, 18, 21, and 24 after treatment with TARA-002
Time Frame
Month 3 to Month 24
Title
Cohort B: Progression free survival after treatment with TARA-002
Time Frame
24 months
Title
Cohort B: Disease-specific progression free survival after treatment with TARA-002
Time Frame
24 months
Title
Cohort B: Overall survival after treatment with TARA-002
Time Frame
24 months
Title
Cohort B: Disease specific survival after treatment with TARA-002
Time Frame
24 months
Title
Cohort B: Time to cystectomy after treatment with TARA-002
Time Frame
24 months
Title
Cohort B: Time to recurrence delayed cystectomy after treatment with TARA-002
Time Frame
24 months
Title
Cohort B: Time to progression after treatment with TARA-002
Time Frame
24 months
Title
Cohort B: Time to disease worsening after treatment with TARA-002
Time Frame
24 months
Title
Cohort B: Incidence and severity of AEs, TEAEs, SAEs and TESAEs after treatment with TARA-002
Time Frame
Day 1 to Month 24
Title
Cohort B: Change from baseline in inflammatory urine cytokines levels (including IL-6, IL-8, IFN-γ, and TNF-α) after treatment with TARA-002
Time Frame
Day 1 to Month 24
Title
Cohort B: Quality of Life based on the EORTC questionnaire QLQ-NMIBC24
Description
EORTC = European Organization for Research and Treatment of Cancer; QLQ-NMIBC24 = Questionnaire for Patients with NMIBC
Time Frame
Day 1 to Month 24
Title
Cohort B: Quality of Life based on the EORTC questionnaire QLQ-C30
Description
EORTC = European Organization for Research and Treatment of Cancer; QLQ-C30 = Questionnaire for Patients with Cancer
Time Frame
Day 1 to Month 24
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
Central histologic confirmation of high-grade non-muscle invasive CIS (± Ta/T1) with active disease
Subjects who are unable to obtain intravesical BCG, have not received intravesical BCG for 24 months prior to CIS diagnosis, or have persistent or recurrent CIS (± Ta/T1) within 12 months of completion of adequate BCG
Exclusion Criteria:
Penicillin allergy (subjects 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 subject's history
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
AccuMed Research Associates
City
Garden City
State/Province
New York
ZIP/Postal Code
11530
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Carolina Urologic Research Center
City
Myrtle Beach
State/Province
South Carolina
ZIP/Postal Code
29572
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Urology Associates PC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37209
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Virginia Urology
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23235
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Arensia Kapitanivka - PPDS
City
Kapitanivka
ZIP/Postal Code
08111
Country
Ukraine
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
12. IPD Sharing Statement
Learn more about this trial
Dose Expansion, Safety and Efficacy Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer
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