BCG Solution with or without PANVAC in Treating Patients with Localized Bladder Cancer

Inclusion Criteria

• Patients must have histologically confirmed localized high grade (G3) transitional cell carcinoma (urothelial carcinoma) of the bladder that is stage Ta, T1, and/or carcinoma in situ (CIS) confirmed by the Laboratory of Pathology, National Cancer Institute (NCI) 90 days prior to study entry; this can be obtained at an outside hospital prior to entry into the study or at the NCI; however, all outside pathology specimens will require that the formalin-fixed paraffin embedded tissues be re-read by the Laboratory of Pathology, NCI; for patients enrolled at collaborating trial sites, diagnosis must be confirmed by the Department of Pathology at the institution where the patient is enrolled on the trial; pathology can also be reviewed by the Laboratory of Pathology at the NCI if the participating trial site prefers another pathologic evaluation
• Patients have failed at least one previous induction course of intravesical BCG, defined as histologically confirmed persistent or relapsing tumor present on post-BCG endoscopic evaluation; all BCG failures will be considered for inclusion into the study, including BCG-refractory, -resistant, and -relapsing; for the purposes of the study, “BCG-refractory” and “BCG-resistant” subjects will be considered to have “BCG-persistent” disease
• Patients who are not currently candidates for radical cystectomy (e.g. patient refuses surgery, comorbidities preclude major surgery, etc.)
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 50,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
• Estimated glomerular filtration rate (GFR) (calculated using Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) >= 30 mL/min/1.73 sq.m.
• Computerized tomography (CT) urogram or magnetic resonance imaging (MRI) urogram; if urogram protocol not available or contrast allergy/poor renal function preclude such imaging, then noncontrast CT or MRI of the abdomen/pelvis within 45 days of study entry will suffice
• Chest x-ray negative for metastatic disease
• Ability of patient to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Previous pelvic radiation for bladder or prostate cancer if performed < 12 months prior to enrollment into the study
• Patients who are receiving any other concurrent investigational agents (patients are eligible to enroll 4 weeks after completion of prior agent)
• Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; there will be at least a 3 week delay from the time of a previous bladder biopsy/transurethral resection of bladder tumor (TURBT) to allow for adequate bladder healing prior to enrollment
• Patients with a history of encephalitis, multiple sclerosis, or seizures within the last year (from seizure disorder or brain metastasis) should be excluded from this clinical trial
• History of allergy or untoward reaction to prior vaccination with vaccinia virus
• Patients should have no evidence of being immunocompromised as listed below: * Human immunodeficiency virus positivity * Active autoimmune diseases requiring treatment or a history of autoimmune disease that might be stimulated by vaccine treatment; patients with endocrine disease that is controlled by replacement therapy including thyroid disease and adrenal disease and vitiligo may be enrolled * History of splenectomy
• Uncontrolled intercurrent illness which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, active second malignancy other than a cancer that has been successfully treated resulting in a high likelihood of long-term survival (e.g. completely resected basal cell or squamous cell carcinoma of the skin, stage 1 renal cell carcinoma treated with partial nephrectomy, treated low risk prostate cancer, etc.), inflammatory bowel disease (e.g. Crohn’s disease or ulcerative colitis), active diverticulitis, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with vaccines; patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately
• Concurrent use of systemic steroids, except for physiologic doses of systemic steroids for replacement or local (topical, nasal, or inhaled) steroid use; limited doses of systemic steroids to prevent intravenous (IV) contrast, allergic reaction, or anaphylaxis (in patients who have known contrast allergies) are allowed; although topical steroids are allowed, steroid eye-drops are contraindicated
• Altered immune function, including immunodeficiency or history of immunodeficiency; eczema; history of eczema, or other eczematoid skin disorders; or those with acute, chronic or exfoliative skin conditions (e.g. atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
• Medical conditions which, in the opinion of the investigators, would jeopardize the patient or the integrity of the data obtained
• Serious hypersensitivity reaction to egg products
• Chronic hepatitis infection, including B and C
• Clinically significant cardiomyopathy or cardiac complications, including recent myocardial infarction or cerebrovascular accident within one year, and/or unstable or uncontrolled angina
• Previous intolerance to BCG intravesical therapy suggested by development of systemic BCG infection in the past and/or grade 4 or greater adverse effect by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0
• Patients unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the day 1 vaccination: (a) children =< 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczematoid skin disorders, or (d) immunocompromised individuals, such as those with human immunodeficiency virus (HIV)