Treatments and/or Procedures

Study Criteria

Inclusion Criteria

  1. Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell
     carcinoma high-grade subtype (mixed histology tumors allowed if transitional cell
     histology is predominant histology).

       1. Cohort A: Histologically confirmed CIS (with or without Ta/T1 disease); Cohort B:
          Histologically confirmed high-grade papillary disease (Ta/T1 only).

       2. Patients are eligible if the diagnostic biopsy was done within 3 months of
          treatment start and a cystoscopy demonstrating no resectable disease was done
          within 6 calendar weeks (inclusive of 48 days) of treatment start (residual CIS
          is acceptable; patients with T1 disease must undergo repeat resection if
          muscularis propria is not present in each biopsy sample). Patients with
          high-grade Ta and/or T1 disease should have complete resection before study
          treatment.

       3. Upper tract imaging within 6 months prior to study entry must not be suspicious
          for upper tract malignancy.

  2. Currently eligible for intravesical BCG therapy.

  3. Age ≥ 18 years.

  4. Performance status: ECOG performance status of 0, 1, or 2.

  5. Laboratory tests performed within 21 days of treatment start:

       1. Absolute neutrophil count (AGC/ANC) ≥ 1,000/µL

       2. Platelets ≥ 100,000/µL [Patients may be transfused to meet this requirement]

       3. Hemoglobin ≥ 8 g/dL [Patients may be transfused to meet this requirement]

       4. Calculated glomerular filtration rate (GFR*) >40 mL/min or Serum creatinine ≤ 1.5
          x ULN

       5. Total bilirubin ≤ 2.0 X ULN

       6. AST, ALT, ALP ≤ 3.0 X ULN

  6. Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction.
     PFT > 50% FEV1 if clinically indicated by the investigator.

  7. Negative serum pregnancy test if female and of childbearing potential
     (non-childbearing is defined as greater than one year postmenopausal or surgically
     sterilized).

  8. Female participants of childbearing potential must adhere to using a medically
     accepted method of birth control prior to screening and agree to continue its use
     during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation)
     and males must agree to use barrier methods of birth control while on study.

  9. Provide signed informed consent and HIPPA authorization and agree to comply with all
     protocol-specified procedures and follow-up evaluations.

       -  using the following Cockcroft-Gault equation to calculate the eGFR for this
          study: eGFR in mL/min = {(140-age in years) x (weight in kg) x F}/(serum
          creatinine in mg/dL x 72) Where F =1 if male; and 0.85 if female

Exclusion Criteria

  1. Prior BCG treatment or known hypersensitivity to BCG. Patients who have received more
     than a single-dose post-operative treatment of mitomycin-C or gemcitabine following
     the most recent screening TURBT/biopsy are excluded.

  2. Concurrent use of other investigational agents (not including FDA-authorized drugs for
     the prevention and treatment of COVID-19).

  3. History of or evidence of muscle-invasive, locally advanced, metastatic and/or
     extravesical bladder cancer or any other cancer within the past 5 years, except:
     adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer,
     adequately treated stage 1 or 2 cancer from which the patient is currently in complete
     remission, or stable prostate cancer (under active surveillance or hormone control).

  4. Symptomatic congestive heart failure (CHF), NYHA (New York Heart Association) Class
     III or IV or other clinical signs of severe cardiac dysfunction.

  5. Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to
     study entry.

  6. History or evidence of uncontrollable CNS disease.

  7. Known HIV-positive.

  8. Active systemic infection requiring parenteral antibiotic therapy. All prior
     infections must have resolved following optimal therapy.

  9. Concurrent febrile illness, active urinary tract infection, active tuberculosis, a
     history of hypotension or anaphylactic reactions.

 10. Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily or
     equivalent).

 11. Women who are pregnant or nursing. Female patients of childbearing potential must have
     a negative pregnancy test and must adhere to using a medically acceptable method of
     birth control prior to screening and agree to continue its use during the study and
     for 30 days after the last dose of study drug, or be surgically sterilized (e.g.,
     hysterectomy or tubal ligation). Women of childbearing potential are defined as any
     female who has experienced menarche and who is NOT permanently sterile or
     postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses
     without an alternative medical cause. Males must agree to use barrier methods of birth
     control while on study and for 90 days post last dose of study drug.

 12. Psychiatric illness/social situations that would limit compliance with study
     requirements.

 13. Other illness that in the opinion of the investigator would exclude the patient from
     participating in this study.