Home-Based Outpatient Model for BCG Delivery to Reduce Undue Burden on Patients Undergoing Treatment for Non-Muscle Invasive Bladder Carcinoma

PRIMARY OBJECTIVES:

I. To evaluate the feasibility of home-based delivery of intravesical BCG therapy as measured by successful administration of BCG therapy in at least four of five in-home induction doses.

II. To evaluate the correct administration of intravesical BCG.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients achieving an adequate therapy regimen, defined as at least five of six induction instillations (including the first in-clinic dose) plus at least two of three maintenance instillations.

II. To evaluate the safety of home-based intravesical BCG, measured by the incidence, type, and severity of treatment-emergent adverse events (TEAEs) graded per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 6.0, including predefined events of interest (symptomatic urinary tract infection \[UTI\], fever > 38.5 °C, urosepsis, local/distant BCG-related granulomatous reactions, reactive arthritis, and moderate- severe lower urinary tract symptoms (LUTS): dysuria, frequency, urgency, hematuria).

III. Compare the cost of home-based therapy to in-office therapy. IV. Assess patient reported outcomes related to IVa. Quality of life; IVb. Satisfaction with care; IVc. Treatment-related burden. V. Measure treatment response defined as the absence of visible tumor during cystoscopy combined with negative urine cytology at 3- and 6-month surveillance points.

OUTLINE:

Patients receive BCG instilled into the bladder, for a goal of 2 hours, once per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo cystoscopy and patients with no cancer identified receive BCG instilled into the bladder, for a goal of 2 hours, once per week for 3 weeks, starting 1-2 weeks post cystoscopy. The first installation is administered in a hospital-based clinical setting for initial observation, all subsequent treatments are delivered in the patient's home by trained home health nurses. Participants receive emergency contact information, including the telephone number for the 24-hour triage line and instructions for contacting the on-call urologist, to report any suspected exposure or treatment-related concerns.

After completion of study treatment, patients are followed up at 3 and 6 months.

• BCG Solution (Biological), also known as Bacillus Calmette Guerin Solution, Bacillus Calmette-Guerin Solution, TICE BCG Solution: Given via installation in the bladder
• Best Practice (Other), also known as standard of care, standard therapy: Receive BCG in a hospital-based clinical setting
• Cystoscopy (Procedure), also known as CS: Undergo cystoscopy
• Home Health Encounter (Other), also known as HH, Home, Home Care Visit, Home Health: Receive BCG installation at home by trained home health nurses
• Survey Administration (Other): Ancillary studies

Primary outcomes

• Successful administration of Bacille Calmette Guerin (BCG) therapy in at least four of five in-home induction doses (feasibility) [Up to 6 months]: Feasibility will be considered achieved if ≥ 85% complete ≥ 4 of 5 induction and ≥ 2 of 3 maintenance doses. Feasibility will be considered acceptable if the lower bound of the 95% confidence interval exceeds the pre-specified threshold of 70%. The estimated completion proportion will be reported with an exact 95% Clopper-Pearson confidence interval.
• Ability to reconstitute TICE BCG [Up to 6 months]: Successful reconstitution of one vial of TICE BCG in 50 mL of sterile preservative-free saline
• Correct installation technique [Up to 6 months]: Defined as administration of reconstituted TICE BCG through a urethral catheter into the bladder.
• Completion of post instillation instructions to attempt to retain the BCG solution [From instillation to voiding, assessed up to 3 hours]: Completion of post instillation instructions to attempt to retain the BCG solution for approximately 2 hours, or until the patient develops a strong urge to urinate. This will be measured in minutes from instillation to voiding and recorded by the research team during a follow-up telephone call.
• Incidence of post BCG adverse events [Up to 6 months]: Defined as evaluation of any symptoms or adverse effects occurring after BCG therapy.

Secondary outcomes

• Proportion of patients achieving an adequate therapy regimen [Up to 6 months]: Defined as at least five of six induction instillations (including the first in-clinic dose) plus at least two of three maintenance instillations.
• Incidence of treatment-emergent adverse events (AE) [Up to 6 months]: Graded per Common Terminology Criteria for Adverse Events version 6.0, including predefined events of interest (symptomatic urinary tract infection, fever > 38.5 °C, urosepsis, local/distant BCG-related granulomatous reactions, reactive arthritis, and moderate- severe lower urinary tract infection: dysuria, frequency, urgency, hematuria). Occupational exposure incidents among trained home health nurses will also be captured. Descriptive statistics will be used for laboratory abnormalities and physical findings. Kaplan-Meier analysis with log-rank tests may be applied descriptively to assess time to first grade ≥ 3 AE.
• Cost of home-based therapy versus in-office therapy [Up to 6 months]: Patient-reported questionnaires will capture direct out-of-pocket expenses, travel and parking costs, time spent commuting, and caregiver involvement. Responses will be analyzed descriptively, and paired comparisons between the in-clinic and home-based settings (for the first induction dose) will be performed. Continuous outcomes (e.g., travel time, caregiver hours) will be compared using paired t-tests or Wilcoxon signed-rank tests, depending on the distribution. Categorical outcomes (e.g., missed work, caregiver assistance) will be compared using McNemar's test.
• Satisfaction with care [Up to 6 months]: Responses will be summarized descriptively and compared between in-clinic and home-based treatment using Wilcoxon signed-rank tests. Exploratory ordinal logistic regression may be used to identify predictors of high satisfaction.
• Treatment-related burden [Up to 6 months]: A treatment burden questionnaire will be administered weekly after each treatment. The questionnaire is Adapted from the Treatment Burden Questionnaire (TBQ) and the Functional Assessment of Cancer Therapy-Bladder (FACTBl).
• Treatment response [Up to 6 months]: Defined as the absence of visible tumor during cystoscopy combined with negative urine cytology at 3- and 6-month surveillance points. Will be summarized as proportions with exact 95% Clopper-Pearson confidence intervals.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* At least 18 years of age at the time of enrollment
* Able and willing to provide signed informed consent, confirming voluntary participation and understanding of study-related information and procedures
* Determined by the investigator to be capable and willing to comply fully with the study protocol, including the independent or assisted completion of required questionnaires
* Pathological confirmation of NMIBC, with transurethral resection of bladder tumor (TURBT) completed within the past 6 weeks. In cases of cT1, the 6-week window may apply from the date of a second TURBT, if performed
* Clinically confirmed to be intermediate or high risk according to the American Urological Association (AUA)/Society of Urologic Oncology (SUO) risk stratification system:

  * Intermediate risk: recurrent low-grade Ta, solitary low-grade Ta > 3 cm, multifocal lowgrade Ta, low-grade T1, or high-grade Ta ≤ 3 cm.
  * High risk: any high-grade T1, recurrent high-grade Ta, high-grade Ta > 3 cm or multifocal, any carcinoma in situ (CIS), any BCG failure in a high-grade patient, any variant histology, lymphovascular invasion, or high-grade prostatic urethral involvement
* Decision to proceed with adjuvant intravesical Bacillus Calmette-Guérin (BCG) therapy
* No exposure to BCG within the previous year
* Subject agreement that their home:

  * is safe;
  * will permit a medical visitor to enter; and
  * has a private space free from pets and small children
* Ability to abstain from voiding for at least two hours
* Resides within the geographical service area of the affiliated home health service supporting the study
* Has reliable access to technology for remote video consultations or telephone communication, enabling necessary follow-up and safety monitoring

Exclusion Criteria:

* History of intravesical Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma within the past 12 months
* Presence of serious systemic conditions or other active diseases (including severe lung disease) that, in the opinion of the investigator, would render the participant unsuitable for the study or compromise the evaluation of safety and tolerability of the study treatment
* Current enrollment in another investigational drug or device study
* History of complicated or traumatic urethral catheterization
* History of severe voiding dysfunction, uncontrolled urinary incontinence or any other condition that may impair adequate BCG dwell time
* Previous severe adverse reaction or intolerance to BCG therapy
* Immunocompromised state (e.g., HIV with CD4 count < 200 cells/mm\^3, solid organ transplant, or active immunosuppressive therapy)
* Significant cognitive impairment or psychiatric disorder that may interfere with adherence to the study protocol
* Pregnant or currently breastfeeding individuals

• Cheryl T Lee, MD, Principal investigator, Ohio State University Comprehensive Cancer Center