Clinical trial NCT03636256: Evaluation of NanoDoce® in Participants With Urothelial Carcinoma
Official title: Phase 1/2 Trial Evaluating the Safety and Tolerability of NanoDoce® Injection and Intravesical Instillation in Subjects With Urothelial Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: NanOlogy, LLC
Sponsor class: INDUSTRY
Collaborators: name: US Biotest, Inc.
First posted: 2018-08-17
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)
timeFrame: Up to End of Treatment (Month 6 for Group 1 and Group 2 Subset, and Day 45 for Group 2)
Secondary outcomes:
measure: Recurrence Free Survival (RFS)
timeFrame: At Months 6, 9, and 12
measure: Disease Progression
timeFrame: Day 45
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: BCG Oncology, PC
state: Arizona
city: Baltimore
country: United States
facility: James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions
state: Maryland
city: New York
country: United States
facility: Columbia University Herbert Irving Comprehensive Cancer Center
state: New York
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
Study officials:
affiliation: BCG Oncology, PC
name: Donald Lamm, MD, FACS
role: PRINCIPAL_INVESTIGATOR
References: