Evaluation of NanoDoce® in Participants With Urothelial Carcinoma

NCT03636256 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: NANODOCE-2017-02
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Recurrence Free Survival (RFS)

  At Months 6, 9, and 12

• Disease Progression

  Day 45

Study Arms (2)

Non-Muscle Invasive Bladder Cancer

EXPERIMENTAL

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); Drug: NanoDoce (intravesical instillation) - Visit 2 Instillation; Drug: NanoDoce (intravesical instillation) - Induction and Maintenance Instillations

Muscle Invasive Bladder Cancer

EXPERIMENTAL

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); Drug: NanoDoce (intravesical instillation) - Visit 2 Instillation; Other: Institutional Standard of Care

Interventions

NanoDoce (direct injection) DRUG

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

Also known as: docetaxel; large surface area microparticle docetaxel

Muscle Invasive Bladder Cancer; Non-Muscle Invasive Bladder Cancer

NanoDoce (intravesical instillation) - Visit 2 Instillation DRUG

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

Also known as: docetaxel; large surface area microparticle docetaxel

Muscle Invasive Bladder Cancer; Non-Muscle Invasive Bladder Cancer

Institutional Standard of Care OTHER

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

Muscle Invasive Bladder Cancer

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations DRUG

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

Also known as: docetaxel; large surface area microparticle docetaxel

Non-Muscle Invasive Bladder Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• NanOlogy, LLC: lead
• US Biotest, Inc.: collaborator

Study Sites (5)

BCG Oncology, PC

Phoenix, Arizona, 85032, United States

Location

James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions

Baltimore, Maryland, 21287, United States

Location

Columbia University Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urogenital Neoplasms; Urologic Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

Docetaxel; Administration, Intravesical; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Administration, Topical; Drug Administration Routes; Drug Therapy; Therapeutics; Combined Modality Therapy

Results Point of Contact

• Title: Dr. Gere diZerega
• Organization: US Biotest, Inc.

gere.dizerega@usbiotest.com

805.595.1300

Study Officials

• Donald Lamm, MD, FACS

  BCG Oncology, PC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: 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).

Study Record Dates

• First Submitted: August 14, 2018
• First Posted: August 17, 2018
• Study Start: April 2, 2019
• Primary Completion: November 2, 2021
• Study Completion: November 2, 2021
• Last Updated: August 14, 2023
• Results First Posted: August 14, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)