This phase I/II trial studies the side effects, best dose, and effectiveness of stereotactic radiotherapy with enfortumab vedotin in treating patients with cisplatin ineligible, muscle invasive bladder cancer that has not spread to other parts of the body (localized). Stereotactic body radiation therapy is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Giving stereotactic radiotherapy with enfortumab vedotin may be safe, tolerable and/or effective in treating patients with localized, cisplatin ineligible, muscle invasive bladder cancer.
Additional locations may be listed on ClinicalTrials.gov for NCT06394570.
Locations matching your search criteria
United States
Texas
Dallas
UT Southwestern/Simmons Cancer Center-DallasStatus: Active
Contact: Tian Zhang
Phone: 214-645-9554
PRIMARY OBJECTIVES:
I. To assess safety (safety lead-in) and efficacy of combined neoadjuvant stereotactic radiotherapy and enfortumab vedotin in cisplatin-ineligible, non-metastatic, muscle invasive bladder cancer planned for radical cystectomy.
II. To assess rate of pathologic complete response (postneoadjuvant [yp] T0N0) at time of radical cystectomy.
SECONDARY OBJECTIVES:
I. To describe the adverse events associated with combined neoadjuvant stereotactic radiotherapy and enfortumab vedotin during study therapy.
II. To assess down-staging at cystectomy of the study neoadjuvant therapy.
EXPLORATORY OBJECTIVES:
I. To correlate circulating tumor markers to treatment response of the neoadjuvant study regimen and following cystectomy.
II. To assess patient reported quality of life during study therapy.
III. To assess completion rate and/or delays of planned cystectomy after study neoadjuvant therapy.
IV. To assess disease free survival after cystectomy for up to 1 year.
OUTLINE: Patients are assigned to 1 of 2 groups.
GROUP I (SEQUENTIAL): Patients receive enfortumab vedotin intravenously (IV) over 30 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days for a total of 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive stereotactic radiotherapy starting within 7 days of cycle 3 day 21 given every other day for a total of 5 treatments in the absence of disease progression or unacceptable toxicity. 2-8 weeks after completion of treatment, patients undergo standard of care radical cystectomy. Patients undergo blood sample collection throughout the study.
GROUP II (CONCURRENT): Patients receive enfortumab vedotin IV over 30 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days for a total of 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive stereotactic radiotherapy starting on cycle 2 day 15, then again on cycle 2 day 17, then weekly for a total of 5 treatments or starting on cycle 1 day 15, then cycle 2 day 15, then weekly for a total of 5 treatments in the absence of disease progression or unacceptable toxicity. Radiation is not given within 3 days of enfortumab vedotin and at least 1 day is given between radiation treatments. 2-8 weeks after completion of treatment, patients undergo standard of care radical cystectomy. Patients undergo blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 90 days then periodically for up to 12 months.
Lead OrganizationUT Southwestern/Simmons Cancer Center-Dallas
Principal InvestigatorTian Zhang
