This phase III trial studies whether different standard treatments for non-muscle invasive bladder cancer (NMIBC) influence outcomes, such as cancer coming back after a period of improvement (recurrence), in patients that did not respond to treatment with bacillus Calmette-Guerin (BCG). For patients with NMIBC that has returned after BCG who do not want surgery to remove their bladder, the standard treatments include nadofaragene firadenovec, gemcitabine with or without docetaxel, mitomycin, retreatment with BCG, or pembrolizumab. Nadofaragene firadenovec may kill tumor cells by blocking a gene that helps cancer form and grow. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Mitomycin is a type of antibiotic that is only used in cancer chemotherapy (antineoplastic antibiotic). It works by damaging the cell's DNA and may kill tumor cells. It is given with sodium bicarbonate which helps lower the acidity of the urine and increase the effectiveness of the mitomycin. BCG a weakened form of the bacterium Mycobacterium bovis that does not cause disease. It is used in a solution to stimulate the immune system in the treatment of bladder cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Comparing different standard treatments for NMIBC may help to determine which treatment regimen is most effective in treating patients that did not response to BCG treatment.
Additional locations may be listed on ClinicalTrials.gov for NCT06929286.
Locations matching your search criteria
United States
New York
New York
Memorial Sloan Kettering Cancer CenterStatus: Active
Contact: Eugene J Pietzak
Phone: 646-422-4781
PRIMARY OBJECTIVE:
I. To determine whether nadofaragene firadenovec improves high-grade recurrence-free-survival, compared with best usual care.
SECONDARY OBJECTIVES:
I. To determine whether nadofaragene firadenovec improves progression-free survival, compared with best usual care.
II. To determine whether nadofaragene firadenovec improves cystectomy-free survival, compared with best usual care.
III. To determine whether nadofaragene firadenovec improves the proportion of patients with carcinoma in situ (CIS) who have a complete response and the duration of complete response, compared with best usual care.
IV. To determine whether nadofaragene firadenovec improves any grade (low- and high-grade) recurrence-free survival, compared with best usual care.
V. To determine the safety and toxicity associated with nadofaragene firadenovec, compared with best usual care.
OUTLINE: Treating urologists are randomized to 1 of 2 arms and patients are assigned to the arm to which their treating urologist was randomized.
ARM I: Patients receive nadofaragene firadenovec intravesically every 3 months for up to 12 months in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive one of the best usual care treatment regimens as per Memorial Sloan Kettering (MSK) Bladder Cancer Working Group consensus treatment algorithm and treating urologist clinical judgement.
GEMCITABINE/DOCETAXEL (GEMDOCE): Patients receive gemcitabine intravesically over 1 hour followed by docetaxel intravesically over 1 hour once a week for up to 6 weeks of induction therapy in the absence of disease progression or unacceptable toxicity. Patients who have a complete response then receive gemdoce intravesical installations once a month for up to 24 months of maintenance therapy in the absence of disease progression or unacceptable toxicity.
BCG RETREATMENT: Patients with previous gemdoce treatment whose last treatment with BCG was > 12 months ago receive retreatment with BCG on study in the absence of disease progression or unacceptable toxicity.
MITOMYCIN: Patients with previous gemdoce treatment whose last treatment with BCG was =< 12 months receive mitomycin intravesically and sodium bicarbonate orally on study in the absence of disease progression or unacceptable toxicity.
GEMCITABINE: Patients receive gemcitabine intravesically twice a week for three weeks followed by one week of rest for a total of twelve installations in the absence of disease progression or unacceptable toxicity.
PEMBROLIZUMAB: Patients receive pembrolizumab intravenously as per Food and Drug Administration label for BCG-unresponsive NMIBC on study in the absence of disease progression or unacceptable toxicity.
GEMDOCE RETREATMENT: Patients receive retreatment with GemDoce on study in the absence of disease progression or unacceptable toxicity.
Additionally, all patients may undergo cystoscopy, bladder biopsy, transurethral resection of bladder tumor (TURBT), urine sample collection, computed tomography (CT), and/or magnetic resonance imaging (MRI) on study.
After completion of study treatment, patients are followed up as per standard clinical care.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorEugene J Pietzak
