Intravesical BCG vs GEMDOCE in NMIBC

ID#: NCT05538663

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 3

Recruitment Status: Recruiting

Start Date: February 07, 2023

End Date: October 01, 2030

Contact Information:
Max Kates, MD
4106140009
Summary: The study hypothesis is that BCG naïve non-muscle invasive bladder cancer (NMIBC) patients treated with intravesical Gemcitabine + Docetaxel (GEMDOCE) will result in a non-inferior event-free survival (EFS) compared to standard treatment with intravesical BCG. The purpose of this study is to test whether Gemcitabine + Docetaxel is a better or worse treatment than the usual BCG therapy approach. The primary objective of this study is to determine the event free survival (EFS) of BCG-naïve high grade non-muscle invasive bladder cancer patients treated with intravesical BCG vs Gemcitabine + Docetaxel. Secondary objectives are as follows: to compare changes in cancer-specific and bladder cancer-specific QOL from baseline to treatment between BCG-naïve high grade NMIBC patients receiving BCG and GEMDOCE, to determine the cystectomy free survival (CFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE, to determine the progression free survival (PFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE, and to determine the safety and toxicity of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.
Eligibility:

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:__

- 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.