Non-muscle Invasive Bladder Cancer
Conditions
Keywords
Non-muscle invasive bladder Cancer, bladder cancer, high grade Ta, high grade NMIBC, carcinoma in situ
Brief summary
TARA-002-101-Ph2 is an open-label study to investigate the safety and efficacy 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 efficacy 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 (within 3 months) prior to signing the 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 who are BCG unresponsive
Interventions
BIOLOGICALTARA-002
All participants will receive 6 weekly instillations of TARA-002 at the established RP2D (First Treatment Period). Participants who are eligible for reinduction after the First Treatment Period will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Participants confirmed to have a complete response after the First Treatment Period will receive 3 additional weekly doses of TARA-002 instillation as maintenance during 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, 18 and 24. Following the Third Treatment Period, all participants will continue to the Follow up Period from Month 27 until Month 60.
Sponsors
Protara Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All participants will receive 6 weekly instillations of TARA-002 at the established RP2D (First Treatment Period). Participants who are eligible for reinduction after the First Treatment Period will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Participants confirmed to have a complete response after the First Treatment Period will receive 3 additional weekly doses of TARA-002 instillation as maintenance during 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, 15,18, and 24. Following the Third Treatment Period, all participants will continue to the Follow up Period from Month 27 until Month 60.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 CIS (± Ta/T1) who are BCG unresponsive.
Exclusion criteria
* Penicillin allergy (participants with a questionable history of allergy to penicillin will undergo penicillin blood allergy testing via central laboratory * Central confirmed variant histology * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A and B: Duration of high-grade Complete Response rate at Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42, 48, 54, and 60 after treatment with TARA-002 | Month 3 to Month 60 | — |
| Cohort A and B: High-grade Complete Response rate at Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 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, 27, 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: Disease-specific progression free survival after treatment with TARA-002 | 60 months | — |
| Cohort A and B: Overall survival after treatment with TARA-002 | 60 months | — |
| Cohort A and B: Disease specific survival after treatment with TARA-002 | 60 months | — |
| 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 | — |
| 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: Time to disease worsening 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: 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-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: 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 |
| Cohort A and B: Time to cystectomy after treatment with TARA-002 | 60 months | — |
Countries
Argentina, Brazil, Canada, Japan, Taiwan, Ukraine, United States
Contacts
CONTACTChief Scientific Operations Officer
STUDY_DIRECTORChief Scientific Operations Officer
Protara Therapeutics
Outcome results
None listed