Evaluation of NanoDoce® in Participants With Urothelial Carcinoma

Study Overview
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Brief Summary
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This is a clinical trial studying the administration of NanoDoce as a direct injection to the bladder wall immediately after tumor resection and as an intravesical instillation. All participants will receive NanoDoce, and will be evaluated for safety and tolerability, as well as the potential effects of NanoDoce on urothelial carcinoma.

Detailed Description
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In this clinical trial, subjects with high-risk non-muscle invasive bladder cancer (NMIBC) or muscle invasive bladder cancer (MIBC), will receive NanoDoce. Subjects will be stratified into two treatment groups, Group 1 (NMIBC) and Group 2 (MIBC). All subjects will receive NanoDoce injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT), followed by an initial NanoDoce intravesical instillation. Once the TURBT resection site is healed (approximately 1 month), Group 1 (NMIBC) subjects will proceed to a 3-month Induction period (6 weekly NanoDoce intravesical instillations, followed by 6 weeks of rest). After the Induction period, following confirmation of non-recurrence, Group 1 subjects will proceed to a 3-month Maintenance period (3 weekly NanoDoce intravesical instillations, followed by 9 weeks of rest). After NanoDoce direct injection and the initial intravesical instillation, Group 2 subjects will proceed to institutional standard of care and will not receive Induction or Maintenance intravesical instillations.

Official Title
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Phase 1/2 Trial Evaluating the Safety and Tolerability of NanoDoce® Injection and Intravesical Instillation in Subjects With Urothelial Carcinoma

Conditions
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Bladder Cancer, Urothelial Carcinoma, Urinary Bladder Neoplasm, Urinary Bladder Cancer, Urogenital Neoplasms, Urologic Neoplasms, Urologic Cancer, Malignant Tumor of the Urinary Bladder, Cancer of the Bladder

Intervention / Treatment
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* Drug: NanoDoce (direct injection)
* Drug: NanoDoce (intravesical instillation) - Visit 2 Instillation
* Other: Institutional Standard of Care
* Drug: NanoDoce (intravesical instillation) - Induction and Maintenance Instillations


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent; Age ≥18 years; Patients with either: High-risk Non-Muscle Invasive Bladder Cancer (NMIBC); Muscle Invasive Bladder Cancer (MIBC); Urothelial carcinoma confirmed by biopsy, urine cytology, computed tomography scan (CT) or other institution-approved diagnostic methodology; All visible tumors removed during bladder resection (TURBT); Performance Status (ECOG) 0-2 at study entry; Life expectancy of at least 6 months; Adequate marrow, liver, and renal function; ANC ≥ 1.5 x 10^9/L; Hemoglobin ≥ 9.5 grams/dL; Platelets ≥ 75 x 10^9/L; Total bilirubin ≤ 1.5x institutional ULN; AST/ ALT ≤ 2.5x institutional ULN; Creatinine ≤ 1.5x institutional ULN; Adequate method of birth control. Exclusion Criteria: Metastatic disease; Previous (within 12 months) or concurrent history of non-bladder malignancy, except for non-melanoma skin cancer; Intravesical therapy within 6 weeks prior to consent (chemotherapy or immunotherapy including BCG administered directly into the bladder); Resection surface area greater than 8 cm2; Upper tract and urethral disease within 18 months; Known hypersensitivity to any of the study drug components or reconstitution components; Pregnant or breastfeeding; Participation in the treatment phase of another clinical trial within 3 months prior to consent; Investigator's opinion of subject's probable noncompliance or inability to understand the trial and/or give adequate informed consent; Ongoing drug or alcohol abuse.

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Open-label, dose rising trial consisting of a dose escalation phase and a dose confirmation phase for direct injection doses. In the dose escalation phase, subjects will be enrolled in sequential cohorts of three subjects starting at the lowest concentration. The dose determined to be most suitable for further evaluation will enroll additional subjects to total up to 12 subjects at that dose level. The study will also dose escalate Groups 1 and 2 for the intravesical instillation of NanoDoce concentrations (2.0 and 3.0 mg/mL).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-Muscle Invasive Bladder Cancer<br>Subjects will be enrolled in sequential, dose escalating cohorts of NanoDoce direct injection (0.75, 1.5, 2.5, or 3.75 mg/mL). Subjects will also receive an initial NanoDoce intravesical instillation at 2.0 or 3.0 mg/mL and additional Induction (6 weekly NanoDoce intravesical instillations, followed by 6 weeks of rest) and Maintenance (3 weekly NanoDoce intravesical instillations, followed by 9 weeks of rest) instillations at 2.0 or 3.0 mg/mL. | Drug: NanoDoce (direct injection)<br>* Subjects will receive NanoDoce injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT)<br>* Other names: docetaxel; large surface area microparticle docetaxel;Drug: NanoDoce (intravesical instillation) - Visit 2 Instillation<br>* All subjects will receive an initial intravesical instillation within 2 hours of direct injection.<br>* Other names: docetaxel; large surface area microparticle docetaxel;Drug: NanoDoce (intravesical instillation) - Induction and Maintenance Instillations<br>* Group 1 (NMIBC) will receive intravesical instillations in an Induction Period and a Maintenance Period.<br>* Other names: docetaxel; large surface area microparticle docetaxel;|
| Experimental: Muscle Invasive Bladder Cancer<br>Subjects will be enrolled in sequential, dose escalating cohorts of NanoDoce direct injection (0.75, 1.5, 2.5, or 3.75 mg/mL). Subjects will also receive an initial NanoDoce intravesical instillation at 2.0 or 3.0 mg/mL. Subjects will then go on to receive institutional standard of care. | Drug: NanoDoce (direct injection)<br>* Subjects will receive NanoDoce injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT)<br>* Other names: docetaxel; large surface area microparticle docetaxel;Drug: NanoDoce (intravesical instillation) - Visit 2 Instillation<br>* All subjects will receive an initial intravesical instillation within 2 hours of direct injection.<br>* Other names: docetaxel; large surface area microparticle docetaxel;Other: Institutional Standard of Care<br>* Group 2 (MIBC) will receive institutional standard of care treatments after the Visit 2 intravesical instillation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) | Treatment Emergent Adverse Events included laboratory assessments, physical examination findings, and vital signs. | Up to End of Treatment (Month 6 for Group 1 and Group 2 Subset, and Day 45 for Group 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence Free Survival (RFS) | No evidence of tumor recurrence or disease progression | At Months 6, 9, and 12 | 
| Disease Progression | Disease progression at Day 45 derived from cytology and biopsy assessments | Day 45 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-muscle invasive bladder cancer, muscle invasive bladder cancer, high-risk bladder cancer, BCG-unresponsive bladder cancer, BCG failure, BCG-refractory bladder cancer, BCG-resistant bladder cancer, NMIBC, MIBC