Evaluation of NanoDoce® in Participants With Urothelial Carcinoma

Phase 1

Completed

• Conditions: Urologic Cancer; Bladder Cancer; Urinary Bladder Cancer; Urogenital Neoplasms; Urinary Bladder Neoplasm; Malignant Tumor of the Urinary Bladder; Urologic Neoplasms; Urothelial Carcinoma; Cancer of the Bladder
• Interventions: Drug: NanoDoce (direct injection); Drug: NanoDoce (intravesical instillation) - Visit 2 Instillation; Other: Institutional Standard of Care; Drug: NanoDoce (intravesical instillation) - Induction and Maintenance Instillations

• Registration Number: NCT03636256
• Lead Sponsor: NanOlogy, LLC

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2018-08-14
• Study First Submitted QC: 2018-08-14
• Study First Posted: 2018-08-17
• Study Start: 2019-04-02
• Primary Completion: 2021-11-02
• Study Completion: 2021-11-02
• Results First Submitted: 2022-12-09
• Status Verified: 2023-07
• Results First Submitted QC: 2023-07-20
• Last Update Submitted: 2023-07-20
• Results First Posted: 2023-08-14
• Last Update Posted: 2023-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Muscle Invasive Bladder Cancer	Institutional Standard of Care	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.
Non-Muscle Invasive Bladder Cancer	NanoDoce (direct injection)	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.
Non-Muscle Invasive Bladder Cancer	NanoDoce (intravesical instillation) - Induction and Maintenance Instillations	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.
Muscle Invasive Bladder Cancer	NanoDoce (intravesical instillation) - Visit 2 Instillation	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.
Non-Muscle Invasive Bladder Cancer	NanoDoce (intravesical instillation) - Visit 2 Instillation	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.
Muscle Invasive Bladder Cancer	NanoDoce (direct injection)	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (5)

Carolina Urologic Research Center; 🇺🇸 Myrtle Beach, South Carolina, United States

BCG Oncology, PC; 🇺🇸 Phoenix, Arizona, United States

Columbia University Herbert Irving Comprehensive Cancer Center; 🇺🇸 New York, New York, United States

James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions; 🇺🇸 Baltimore, Maryland, United States

UT Health San Antonio; 🇺🇸 San Antonio, Texas, United States