Intravesical BCG vs GEMDOCE in NMIBC

Inclusion Criteria:

• Patient must be > 18 years of age.

• Patient must have histologically confirmed high-grade non-muscle invasive urothelialcarcinoma of the bladder (HgTa, HGT1, CIS, HgTa + CIS, or HGT1 + CIS stage) ontransurethral resection of bladder tumor (TURBT) obtained within 90 days prior torandomization.

• Patient must have all visible papillary tumor resected by the treating urologist atthe site registering the patient to this protocol prior to randomization. If thetreating urologist did not perform the TURBT as outlined in Section 3.1.3, thetreating urologist must perform a cystoscopy within 28 days prior to randomizationto confirm the absence of visible papillary disease.

• Patient must have not received prior intravesical therapy for bladder cancer, withthe exception of perioperative chemotherapy at the time of TURBT.

• Patients with high grade T1 disease must have undergone a restaging TURBT within 90days 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 orlarge cell).

• Patient must not have any component of sarcomatoid, micropapillary, or plasmacytoidvariant histology.

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe 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 fora non-bladder malignancy.

• Patient must have the ability to understand and the willingness to sign a writteninformed consent document. Patients with impaired decision-making capacity (IDMC)who have a legally authorized representative (LAR) or caregiver and/or family memberavailable will also be considered eligible.

• Patient must have adequate organ and marrow function as defined below (these labsmust 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-retroviraltherapy with undetectable viral load within 6 months of randomization are eligiblefor this trial.

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated.

• Patients with a history of hepatitis C virus (HCV) infection must have been treatedand cured. For patients with HCV infection who are currently on treatment, they areeligible if they have an undetectable HCV viral load.

• Patients with known history or current symptoms of cardiac disease, or history oftreatment with cardiotoxic agents, should have a clinical risk assessment of cardiacfunction using the New York Heart Association Functional Classification. To beeligible 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 assessedon radiographic imaging obtained within 90 days prior to randomization. Theradiographic imaging includes a CT Scan OR MRI of the abdomen/pelvis withintravenous 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 andeffective method(s) of contraception or by abstaining from sexual intercourse forthe duration of their participation in the study. In addition,patients on Arm A mustcontinue contraception measures for six months after the last dose of GEMDOCE forpatients of child-bearing potential and continue for three month after the last doseof GEMDOC for male patients with partners of child-bearing potential. All patientsmust not breastfeed during their time on protocol treatment.

• Patient must not have a history of severe hypersensitivity reactions to docetaxel ordrugs formulated with polysorbate 80.