Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

BCG Vaccine

Tubulin Modulators

Antimitotic Agents

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.

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.

Subjects will receive NanoDoce injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT)

NanoDoce (direct injection)

All subjects will receive an initial intravesical instillation within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Visit 2 Instillation

Group 2 (MIBC) will receive institutional standard of care treatments after the Visit 2 intravesical instillation.

Institutional Standard of Care

Group 1 (NMIBC) will receive intravesical instillations in an Induction Period and a Maintenance Period.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations

Donald Lamm, MD, FACS

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.

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.

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).

Evaluation of NanoDoce® in Participants With Urothelial Carcinoma

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

Treatment Emergent Adverse Events included laboratory assessments, physical examination findings, and vital signs.

No evidence of tumor recurrence or disease progression

Disease progression at Day 45 derived from cytology and biopsy assessments

US Biotest, Inc.

NanOlogy, LLC

Subjects were required to spontaneously report any AEs. Study personnel asked open-ended questions to obtain information about AEs at every visit.

NanoDoce (direct injection): Subjects received NanoDoce 0.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce at 2.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subjects received intravesical instillations of NanoDoce in an Induction Period (6 weekly NanoDoce intravesical instillations at 2.0 mg/mL or 3.0 mg/mL, followed by 6 weeks of rest) and a Maintenance Period (3 weekly NanoDoce intravesical instillations at 3.0 mg/mL, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL or 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Non-Muscle Invasive Bladder Cancer (Group 1) 0.75 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 1.5 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce at 2.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subjects received intravesical instillations of NanoDoce in an Induction Period (6 weekly NanoDoce intravesical instillations at 2.0 mg/mL or 3.0 mg/mL, followed by 6 weeks of rest) and a Maintenance Period (3 weekly NanoDoce intravesical instillations at 3.0 mg/mL, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL or 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Non-Muscle Invasive Bladder Cancer (Group 1) 1.5 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 2.5 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce at 2.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subjects received intravesical instillations of NanoDoce in an Induction Period (6 weekly NanoDoce intravesical instillations at 2.0 mg/mL or 3.0 mg/mL, followed by 6 weeks of rest) and a Maintenance Period Maintenance (3 weekly NanoDoce intravesical instillations at 3.0 mg/mL, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL or 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Non-Muscle Invasive Bladder Cancer (Group 1) 2.5 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 3.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce at 2.0 or 3.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subjects received intravesical instillations of NanoDoce in an Induction Period (6 weekly NanoDoce intravesical instillations at 2.0 or 3.0 mg/mL, followed by 6 weeks of rest) and a Maintenance Period Maintenance (3 weekly NanoDoce intravesical instillations at 3.0 mg/mL, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL or 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Non-Muscle Invasive Bladder Cancer (Group 1) 3.75 mg/mL

NanoDoce (direct injection): Subject received NanoDoce 3.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subject received an initial intravesical instillation of NanoDoce at 3.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subject received intravesical instillations of NanoDoce at 3.0 mg/mL in an Induction Period (6 weekly NanoDoce intravesical instillations, followed by 6 weeks of rest) and a Maintenance Period (3 weekly NanoDoce intravesical instillations, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Muscle Invasive Bladder Cancer (Group 2) Subset 3.75 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 0.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an intravesical instillation of NanoDoce 2.0 mg/mL within 2 hours of direct injection. Total dose administered for intravesical instillation could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL.

Muscle Invasive Bladder Cancer (Group 2) 0.75 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 1.5 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an intravesical instillation of NanoDoce 2.0 mg/mL within 2 hours of direct injection. Total dose administered for intravesical instillation could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL.

Muscle Invasive Bladder Cancer (Group 2) 1.5 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 2.5 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce 2.0 mg/mL within 2 hours of direct injection. Total dose administered for intravesical instillation could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL.

Muscle Invasive Bladder Cancer (Group 2) 2.5 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 3.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation): Subjects received an initial intravesical instillation of NanoDoce 3.0 mg/mL within 2 hours of direct injection. Total dose administered for intravesical instillation could not exceed 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Muscle Invasive Bladder Cancer (Group 2) 3.75 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 2.5 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce at 2.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subjects received intravesical instillations of NanoDoce in an Induction Period (6 weekly NanoDoce intravesical instillations at 2.0 mg/mL or 3.0 mg/mL, followed by 6 weeks of rest) and a Maintenance Period (3 weekly NanoDoce intravesical instillations at 3.0 mg/mL, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL or 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

NanoDoce (direct injection): Subjects received NanoDoce 3.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce at 2.0 or 3.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subjects received intravesical instillations of NanoDoce in an Induction Period (6 weekly NanoDoce intravesical instillations at 2.0 or 3.0 mg/mL, followed by 6 weeks of rest) and a Maintenance Period (3 weekly NanoDoce intravesical instillations at 3.0 mg/mL, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL or 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

NanoDoce (direct injection): Subjects received NanoDoce 2.5 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an intravesical instillation of NanoDoce 2.0 mg/mL within 2 hours of direct injection. Total dose administered for intravesical instillation could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL.

NanoDoce (direct injection): Subjects received NanoDoce 3.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an intravesical instillation of NanoDoce 3.0 mg/mL within 2 hours of direct injection. Total dose administered for intravesical instillation could not exceed 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Gere diZerega

Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)

Non-Muscle Invasive Bladder Cancer - 0.75 mg/mL NanoDoce Injection Cohort

Non-Muscle Invasive Bladder Cancer - 1.5 mg/mL NanoDoce Injection Cohort

Non-Muscle Invasive Bladder Cancer - 2.5 mg/mL NanoDoce Injection Cohort

Non-Muscle Invasive Bladder Cancer - 3.75 NanoDoce Injection Cohort

All subjects from the NMIBC Group 1 were evaluated for RFS. No subjects in the MIBC Group 2 or MIBC Group 2 Subset were evaluated for RFS.

Recurrence Free Survival (RFS)

Muscle Invasive Bladder Cancer - 0.75 mg/mL NanoDoce Injection Cohort

Muscle Invasive Bladder Cancer - 1.5 mg/mL NanoDoce Injection Cohort

Muscle Invasive Bladder Cancer - 2.5 mg/mL NanoDoce Injection Cohort

Muscle Invasive Bladder Cancer - 3.75 NanoDoce Injection Cohort

Muscle Invasive Bladder Cancer Subset (Group 2 Subset) - 3.75/mg/mL NanoDoce Injection

The muscle invasive bladder cancer (MIBC) (Group 2) and MIBC Group 2 Subset were assessed for disease progression at Day 45. There were two subjects in the 3.75 mg/mL NanoDoce cohort for whom disease status at Day 45 was unknown, and there were two subjects withdrawn from the study prior to analysis of disease progression at Day 45.

Spots Global Cancer Trial Database for malignant tumor of the urinary bladder