Evaluation of NanoDoce® in Participants With Urothelial Carcinoma

Sponsor

NanOlogy, LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT03636256

Collaborator

US Biotest, Inc. (Industry)

Enrollment

Locations

Arms

Actual Duration (Months)

7.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: NanoDoce (direct injection) Drug: NanoDoce (intravesical instillation) - Visit 2 Instillation Other: Institutional Standard of Care Drug: NanoDoce (intravesical instillation) - Induction and Maintenance Instillations	Phase 1/Phase 2

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 of Maintenance intravesical instillations.

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention 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).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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 2, 2019

Actual Primary Completion Date :

Nov 2, 2021

Actual Study Completion Date :

Nov 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Non-Muscle Invasive Bladder Cancer 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) Subjects will receive NanoDoce injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT) Other Names: docetaxel Drug: NanoDoce (intravesical instillation) - Visit 2 Instillation All subjects will receive an initial intravesical instillation within 2 hours of direct injection. Other Names: docetaxel Drug: NanoDoce (intravesical instillation) - Induction and Maintenance Instillations Group 1 (NMIBC) will receive intravesical instillations in an Induction Period and a Maintenance Period. Other Names: docetaxel
Experimental: Muscle Invasive Bladder Cancer 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) Subjects will receive NanoDoce injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT) Other Names: docetaxel Drug: NanoDoce (intravesical instillation) - Visit 2 Instillation All subjects will receive an initial intravesical instillation within 2 hours of direct injection. Other Names: docetaxel Other: Institutional Standard of Care Group 2 (MIBC) will receive institutional standard of care treatments after the Visit 2 intravesical instillation.

Arm

Intervention/Treatment

Experimental: Non-Muscle Invasive Bladder Cancer

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)

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

Other Names:

docetaxel

Drug: NanoDoce (intravesical instillation) - Visit 2 Instillation

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

Other Names:

docetaxel

Drug: NanoDoce (intravesical instillation) - Induction and Maintenance Instillations

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

Other Names:

docetaxel

Experimental: Muscle Invasive Bladder Cancer

Drug: NanoDoce (direct injection)

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

Other Names:

docetaxel

Drug: NanoDoce (intravesical instillation) - Visit 2 Instillation

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

Other Names:

docetaxel

Other: Institutional Standard of Care

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

Outcome Measures

Primary Outcome Measures

Incidence of Treatment Emergent Adverse Events (safety and tolerability) [Up to End of Treatment (Month 6 for Group 1 and Day 45 for Group 2)]
Treatment Emergent Adverse Events will include laboratory assessments, physical examination findings, and vital signs.

Secondary Outcome Measures

Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) of NanoDoce [Up to End of Treatment (Month 6 for Group 1 and Day 45 for Group 2)]
Plasma samples will be collected to characterize the pharmacokinetics of NanoDoce.
Pharmacokinetics: Peak plasma concentration (Cmax) of NanoDoce [Up to End of Treatment (Month 6 for Group 1 and Day 45 for Group 2)]
Plasma samples will be collected to characterize the pharmacokinetics of NanoDoce.
Pharmacokinetics: Time at which peak plasma concentration is observed (Tmax) of NanoDoce. [Up to End of Treatment (Month 6 for Group 1 and Day 45 for Group 2)]
Plasma samples will be collected to characterize the pharmacokinetics of NanoDoce.
Progression free survival (PFS) [At Months 6, 9, and 12]
No evidence of tumor recurrence or disease progression

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BCG Oncology, PC	Phoenix	Arizona	United States	85032
2	James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions	Baltimore	Maryland	United States	21287
3	Columbia University Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
4	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
5	UT Health San Antonio	San Antonio	Texas	United States	78229