Evaluation of NanoDoce® in Participants With 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.

• NanoDoce (direct injection) (Drug), also known as docetaxel; large surface area microparticle docetaxel: 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 (intravesical instillation) - Visit 2 Instillation (Drug), also known as docetaxel; large surface area microparticle docetaxel: All subjects will receive an initial intravesical instillation within 2 hours of direct injection.
• Institutional Standard of Care (Other): Group 2 (MIBC) will receive institutional standard of care treatments after the Visit 2 intravesical instillation.
• NanoDoce (intravesical instillation) - Induction and Maintenance Instillations (Drug), also known as docetaxel; large surface area microparticle docetaxel: Group 1 (NMIBC) will receive intravesical instillations in an Induction Period and a Maintenance Period.

Primary outcomes

• 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 outcomes

• 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

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) (Primary), Count of participants, Participants: Non-Muscle Invasive Bladder Cancer (Group 1) 0.75 mg/mL 3; Non-Muscle Invasive Bladder Cancer (Group 1) 1.5 mg/mL 3; Non-Muscle Invasive Bladder Cancer (Group 1) 2.5 mg/mL 3; Non-Muscle Invasive Bladder Cancer (Group 1) 3.75 mg/mL 9; Muscle Invasive Bladder Cancer (Group 2) Subset 3.75 mg/mL 1; Muscle Invasive Bladder Cancer (Group 2) 0.75 mg/mL 5; Muscle Invasive Bladder Cancer (Group 2) 1.5 mg/mL 2; Muscle Invasive Bladder Cancer (Group 2) 2.5 mg/mL 1; Muscle Invasive Bladder Cancer (Group 2) 3.75 mg/mL 6
• Recurrence Free Survival (RFS) (Secondary), Mean, Months: Non-Muscle Invasive Bladder Cancer - 0.75 mg/mL NanoDoce Injection Cohort 5.1 +/- 1.79; Non-Muscle Invasive Bladder Cancer - 1.5 mg/mL NanoDoce Injection Cohort 6.7 +/- 3.10; Non-Muscle Invasive Bladder Cancer - 2.5 mg/mL NanoDoce Injection Cohort 4.7 +/- 1.10; Non-Muscle Invasive Bladder Cancer - 3.75 NanoDoce Injection Cohort 9.6 +/- 3.31
• Disease Progression (Secondary), Count of participants, Participants: Muscle Invasive Bladder Cancer - 0.75 mg/mL NanoDoce Injection Cohort 2; Muscle Invasive Bladder Cancer - 1.5 mg/mL NanoDoce Injection Cohort 1; Muscle Invasive Bladder Cancer - 2.5 mg/mL NanoDoce Injection Cohort 0; Muscle Invasive Bladder Cancer - 3.75 NanoDoce Injection Cohort 1; Muscle Invasive Bladder Cancer Subset (Group 2 Subset) - 3.75/mg/mL NanoDoce Injection 0

Adverse events

Time frame: AE were captured from first study drug dose (injection) until 45 days after the last study drug dose (injection or instillation) for Group 2 subjects or until the End of Treatment (Visit 13 - Day 180) visit for Group 1 or Group 2 subset subjects. Subjects were required to spontaneously report any AEs. Study personnel asked open-ended questions to obtain information about AEs at every visit.

Serious adverse events by term

Other adverse events by term

48 more terms not shown.

• Study Protocol (PDF, 2020-06-18)
• Statistical Analysis Plan (PDF, 2021-12-03)

• Donald Lamm, MD, FACS, Principal investigator, BCG Oncology, PC