A Phase III Randomized Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming with Intradermal BCG Before Intravesical Therapy for BCG-Naïve High-Grade Non-Muscle Invasive Bladder Cancer

This randomized phase III trial studies Tokyo-172 strain bacillus Calmette-Guerin (BCG)
solution with or without a vaccination using Tokyo-172 strain BCG to see how well it works
compared with TICE BCG solution in treating patients with bladder cancer that has not spread
to muscle. BCG is a non-infectious bacteria that when instilled into the bladder may
stimulate the immune system to fight bladder cancer. Giving different versions of BCG with
vaccine therapy may prevent bladder cancer from returning.

Inclusion Criteria:

- Patients must have histologically proven Ta, carcinoma in situ (CIS) or T1 stage
urothelial cell carcinoma of the bladder within 90 days of registration

- Patients must have had all grossly visible papillary tumors removed within 30 days
prior to registration or cystoscopy confirming no grossly visible papillary tumors
within 30 days prior to registration

- Patients with T1 disease must have cross-sectional imaging of abdomen/pelvis
demonstrating no evidence of metastatic disease (magnetic resonance imaging [MRI] or
computed tomography [CT] scan) within 90 days prior to registration; patients with T1
disease must have re-resection confirming =< T1 disease within 90 days prior to
registration

- Patients must have high-grade bladder cancer as defined by 2004 World Health
Organization (WHO)/International Society of Urological Pathology (ISUP) classification

- Patients must not have pure squamous cell carcinoma or adenocarcinoma

- Patients' disease must not have micropapillary components

- Patients must have no evidence of upper tract (renal pelvis or ureters) cancer
confirmed by one of the following tests performed within 90 days prior to
registration: CT urogram, intravenous pyelogram, magnetic resonance (MR) urogram, or
retrograde pyelograms

- Patients must not have nodal involvement or metastatic disease

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
stage I or II cancer from which the patient is currently in complete remission, or any
other cancer from which the patient has been disease free for five years; patients
with localized prostate cancer who are being followed by an active surveillance
program are also eligible

- Patients must have a Zubrod performance status of 0-2

- Patients must not have received prior intravesical BCG

- Patients must not have known history of tuberculosis

- Patients must be PPD negative within 90 days prior to registration; PPD negativity is
defined as < 10 mm diameter induration (palpable, raised hardened area) in the volar
forearm at 48-72 hours following injection with standard tuberculin dose (5 units, 0.1
ml)

- Patients must be >= 18 years of age

- Patients must not be taking oral glucocorticoids at the time of registration

- Patients must not be planning to receive concomitant biologic therapy, hormonal
therapy, chemotherapy, surgery, or other cancer therapy while on study

- Prestudy history and physical must be obtained within 90days prior to registration

- Patients must not be pregnant or nursing; women/men of reproductive potential must
have agreed to use an effective contraceptive method; a woman is considered to be of
"reproductive potential" if she has had menses at any time in the preceding 12
consecutive months; in addition to routine contraceptive methods, "effective
contraception" also includes heterosexual celibacy and surgery intended to prevent
pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
bilateral oophorectomy or bilateral tubal ligation; however, if at any point a
previously celibate patient chooses to become heterosexually active during the time
period for use of contraceptive measures outlined in the protocol, he/she is
responsible for beginning contraceptive measures

- Patients must be offered the opportunity to participate in specimen banking for future
studies to include translational medicine studies