A Randomized Phase III Trial oflntravesical BCG veRsus Intravesical Docetaxel and GEmcitabine Treatment in BCG Naive High Grade Non-Muscle Invasive Bladder Cancer (BRIDGE).

Inclusion Criteria

- Patient must be > 18 years of age.

- Patient must have histologically confirmed high-grade non-muscle invasive urothelial

carcinoma of the bladder (HgTa, HGT1, CIS, HgTa + CIS, or HGT1 + CIS stage) on

transurethral resection of bladder tumor (TURBT) obtained within 90 days prior to

randomization.

- Patient must have all visible papillary tumor resected by the treating urologist at

the site registering the patient to this protocol prior to randomization. If the

treating urologist did not perform the TURBT as outlined in Section 3.1.3, the

treating urologist must perform a cystoscopy within 28 days prior to randomization to

confirm the absence of visible papillary disease.

- Patient must have not received prior intravesical therapy for bladder cancer, with the

exception of perioperative chemotherapy at the time of TURBT.

- Patients with high grade T1 disease must have undergone a restaging TURBT within 90

days prior to Step 1 randomization.

NOTE: Patients with high grade T1 disease who undergo a restaging TURBT that shows no

residual cancer in the restaging TURBT specimen are eligible.

- Patient must not have pure squamous cell carcinoma or adenocarcinoma.

- Patient must not have any component of neuroendocrine carcinoma (i.e., small cell or

large cell).

- Patient must not have any component of sarcomatoid, micropapillary, or plasmacytoid

variant histology.

- Patients with a prior or concurrent malignancy whose natural history or treatment does

not have the potential to interfere with the safety or efficacy assessment of the

investigational regimen are eligible for this trial.

- Patient must have ECOG Performance Status 0-2.

- Patient may have received prior systemic gemcitabine or docetaxel use if it was for a

non-bladder malignancy.

- Patient must have the ability to understand and the willingness to sign a written

informed consent document. Patients with impaired decision-making capacity (IDMC) who

have a legally authorized representative (LAR) or caregiver and/or family member

available will also be considered eligible.

- Patient must have adequate organ and marrow function as defined below (these labs must

be obtained ≤ 28 days prior to randomization):

Leukocytes ≥ 3,000/mcL Leukocytes:__________ Date of Test:__________ Absolute neutrophil

count (ANC) ≥ 1,500/mcL ANC:__________ Date of Test:__________ Platelets ≥ 70,000/mcL

Platelets:__________ Date of Test:__________ Total Bilirubin ≤ institutional upper limit of

normal (ULN) Total Bilirubin:__________ Institutional ULN:_________ Date of Test:__________

AST(SGOT)/ALT(SGPT) ≤ 3.0 × institutional ULN AST:_______ Institutional ULN:_________ Date

of Test:_______ ALT: _______Institutional ULN:_________

- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral

therapy with undetectable viral load within 6 months of randomization are eligible for

this trial.

- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral

load must be undetectable on suppressive therapy, if indicated.

- Patients with a history of hepatitis C virus (HCV) infection must have been treated

and cured. For patients with HCV infection who are currently on treatment, they are

eligible if they have an undetectable HCV viral load.

- Patients with known history or current symptoms of cardiac disease, or history of

treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac

function using the New York Heart Association Functional Classification. To be

eligible for this trial, patients should be class 2B or better.

Exclusion Criteria

- Patient must not have any prior or current history of muscle-invasive (i.e., T2, T3,

T4), locally advanced unresectable, or metastatic urothelial carcinoma as assessed on

radiographic imaging obtained within 90 days prior to randomization. The radiographic

imaging includes a CT Scan OR MRI of the abdomen/pelvis with intravenous contrast.

NOTE: If a patient's renal function does not permit the administration of intravenous

contrast, either a CT scan or MRI of the abdomen/pelvis without intravenous contrast is

acceptable.

NOTE: Patients with a history of non-invasive (Ta, Tis) upper tract urothelial carcinoma

that has been definitively treated with at least one post-treatment disease assessment

(i.e., either cytology, biopsy, or imaging) that demonstrates no evidence of residual

disease are eligible.

- Patient must not be pregnant or breast-feeding due to the potential harm to an unborn

fetus and possible risk for adverse events in nursing infants with the treatment regimens

being used.

All patients of childbearing potential must have a blood test or urine study within 14 days

prior to randomization to rule out pregnancy.

A patient of childbearing potential is defined as anyone, regardless of sexual orientation

or whether they have undergone tubal ligation, who meets the following criteria: 1) has

achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral

oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer

therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e.,

has had menses at any time in the preceding 24 consecutive months).

Patient of child bearing potential? ______ (Yes or No) Date of blood test or urine study:

___________

- Patient must not expect to conceive or father children by using an accepted and

effective method(s) of contraception or by abstaining from sexual intercourse for the

duration of their participation in the study. In addition,patients on Arm A must

continue contraception measures for six months after the last dose of GEMDOCE for

patients of child-bearing potential and continue for three month after the last dose

of GEMDOC for male patients with partners of child-bearing potential. All patients

must not breastfeed during their time on protocol treatment.

- Patient must not have a history of severe hypersensitivity reactions to docetaxel or

drugs formulated with polysorbate 80.