Multicenter Clinical Trial of ST-02 for Ablation of Upper Tract Urothelial Carcinoma

Study Overview
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Brief Summary
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The goal of this prospective clinical trial is to investigate the safety and efficacy of ST-02 (mucoadhesive gemcitabine suspension for pyelocaliceal instillation) to treat Upper Tract Urothelial Carcinoma (UTUC) in participants who have a low-grade tumor. The main questions this study aims to answer are: Can ST-02 effectively eradicate UTUC by 3 months? Is ST-02 safe for patients with UTUC? Participants in this study will receive ST-02, a new formulation with gemcitabine once weekly for six weeks. Gemcitabine is known to be an effective drug in treating urothelial carcinoma. This new formulation will be instilled directly into the upper urinary tract (renal pelvis) and will allow the chemotherapeutic to work locally for an extended period of time. The administration process will be retrograde (via a small catheter inserted up into the kidney, under anesthesia) or antegrade (via a nephrostomy, in the clinic) once weekly for six weeks. Safety and efficacy will be monitored for up to a year after the initial response assessment.

Detailed Description
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This study is a prospective, multicenter, single-arm, open-label clinical trial assessing the safety and efficacy of ST-02 (mucoadhesive gemcitabine suspension for pyelocaliceal instillation) to chemo-ablate low-grade urothelial carcinoma of the upper urinary tract. Participants with biopsy confirmed low-grade (LG) upper tract urothelial carcinoma (UTUC) and a tumor of 5 to 15 mm will receive 6 weekly instillations of ST-02. The primary objective is to evaluate complete response (CR) at 3 months from the first instillation during the primary tumor evaluation (PTE) visit. This is done by ureteroscopy, and cytology, with or without biopsy if a tumor remains. If the participant presents as a CR, they will receive their first maintenance instillation of ST-02. Endoscopic monitoring of the upper tract with ureteroscopy for responders will be performed every 3 months for up to 12 months after CR, and the patient will receive a single instillation of ST-02 if no recurrence is noted each time. Participants who do not have a CR will be treated by their physician with the standard of care, such as biopsy and laser ablation, and with any additional surgical procedure or treatment as deemed necessary by the Principal Investigator (PI). The first stage of the trial will enroll 30 patients. If there are 8 or fewer CR among these 30 participants, the study will be stopped. Otherwise, an additional 40 participants will be accrued into phase 3, resulting in a total sample size of 70. The durability of response, event-free survival, safety, and other outcomes will also be measured.

Official Title
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A Phase 2/3 Multicenter Trial Evaluating the Safety and Efficacy of ST-02 (Mucoadhesive Gemcitabine Suspension) on Ablation of Urothelial Carcinomas in the Upper Urinary Tract

Conditions
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Urothelial Carcinoma of the Renal Pelvis and Ureter, Transitional Cell Cancer of the Renal Pelvis and Ureter

Intervention / Treatment
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* Drug: ST-02


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (≥ 18 years) male or female Primary or recurrent low-grade (LG), noninvasive (Ta) Upper Tract Urothelial Carcinoma (UTUC) in the renal pelvis, infundibulum, and/or calyces, based on ureteroscopy, biopsy and cytology performed within 8 weeks prior to the Screening Visit At least 1 measurable papillary tumor measuring 5-15 mm Low grade tumor(s) in the ipsilateral ureter. Every attempt should be made to ablate this tumor completely, but residual ipsilateral ureteral tumor is not an exclusion criterion. Prior fully ablated low grade bladder tumor(s), without the need for intravesical therapy except for single-dose chemotherapy A life expectancy of greater than 12 months No active untreated urinary tract infection (UTI) as confirmed by urine culture or urinalysis Women of Child bearing potential (WoCBP) and Males who have a WoCBP partner require a negative pregnancy test at the Screening visit and must use two acceptable contraceptives methods until six months post-treatment All sexually active males must agree to use a condom during intercourse, for at least 48 h after each instillation Exclusion Criteria: Have received Bacillus Calmette - Guerin (BCG) treatment for UTUC within 6 weeks prior to Visit 1 Pregnant (positive urine pregnancy test), planning pregnancy during trial, breast-feeding, or of childbearing potential without reliable contraception Unresolved infection requiring active treatment with systemic antimicrobial drugs History of high-grade non-muscle invasive bladder cancer within the past 6 months History of muscle-invasive bladder cancer during the past 2 years Actively being treated or intend to be treated with intravesical or systemic chemotherapy during the duration of the trial Urinary obstruction in the ipsilateral Upper Urinary Tract (UUT) Any contraindicated to gemcitabine or sensitivity to gemcitabine or any of the ST-02 ingredients Currently receiving another investigational agent or involved in a clinical trial with an investigational product within the past 30 days prior to Visit 1 Active hepatitis B (chronic or acute) or active hepatitis C infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ST-02<br>ST-02 is a new gemcitabine formulation for instillation into the upper urinary tract. Eligible participants will be enrolled and receive ST-02 once weekly for six weeks in a retrograde or antegrade fashion at the discretion of the treating urologist. | Drug: ST-02<br>* ST-02 drug instillation into the upper urinary tract (renal pelvis)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) rate at the Primary Tumor Evaluation (PTE) visit | To evaluate the tumor ablative effect (CR after 3 months) of six instillations of ST-02 in the upper urinary tract of participants with UTUC. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Durable efficacy | To evaluate the durability of tumor ablative effect 12 months after CR in participants who demonstrated complete response at 3 months after instillation of six doses of ST-02 | 12 months after CR | 
| Objective Response Rate (ORR) | To evaluate the objective response rate after treatment with ST-02, defined as proportion of participants with Complete Response (CR) or Partial Response (PR) at the PTE Visit | 3 months | 
| Event-Free Survival (EFS) | To evaluate the event-free survival after treatment with ST-02 | 15 months | 
| Number of adverse event | To evaluate the safety and tolerability of instillation of ST-02 in participants with UTUC | 15 months | 
| Peak Plasma Concentration (Cmax) | To assess the peak concentration of gemcitabine in urine and plasma at 0, 1, 2, 4 and 24 hours after instillation (10 patients, phase 2 only) | 24 hours | 
| Pharmacokinetics (Tmax) | To assess the time to maximal concentration of gemcitabine in urine and plasma at 0, 1, 2, 4 and 24 hours after instillation (10 patients, phase 2 only) | 24 hours | 
| Rate of invasive surgery | To evaluate the rate of nephroureterectomy following instillation of ST-02 | 15 months | 
| Clinical impact of PR in not endoscopically resectable UTUC | To evaluate the proportion of participants with PR whose tumors were considered not endoscopically resectable at baseline but are endoscopically resectable after treatment with ST-02 | 3 months |