This phase I/II trial tests the safety, best dose, and effectiveness of nisin in changing the microorganisms in the oral cavity (oral microbiome) of patients with oral cavity squamous cell cancer. Oral cavity squamous cell cancer, which accounts for approximately 90% of all oral cancers, has a steadily increasing incidence over the past decade. Although surgical resection and adjuvant radiotherapy can lead to a complete cure of early-stage disease, oral cavity squamous cell cancer is often diagnosed at later stages, at which point these therapeutic approaches are not highly effective. The oral microbiome, particularly its bacteria, may be important in oral cancer growth and development. Oral bacteria associated with periodontal disease enhance cancer cell migration and invasion. Nisin, a natural food preservative, has potent broad-spectrum antimicrobial activity, which allows it to interfere with the structure and function of disease-causing microbes in the mouth. Information gained from this trial may allow researchers to determine the safety and effect of nisin on patients' oral health and oral cavity squamous cell cancer.
Additional locations may be listed on ClinicalTrials.gov for NCT06097468.
Locations matching your search criteria
United States
California
San Francisco
University of California San FranciscoStatus: Active
Contact: Sue Sun Yom
Phone: 415-353-7175
PRIMARY OBJECTIVES:
I. To demonstrate the tolerability of nisin administration, as assessed by the maximum tolerated dose (MTD) of nisin. (Phase I [dose finding, Group 1])
II. To demonstrate the feasibility of nisin administration, as assessed by the treatment completion rate. (Phase IIa [dose expansion, Group 2])
SECONDARY OBJECTIVES:
I. To evaluate the safety of nisin administration, as assessed by the frequency and severity of adverse events (Common Terminology Criteria for Adverse Events [CTCAE] 5.0). (Phase I [dose finding, Group 1] and Phase IIa [dose expansion, Group 2])
II. To evaluate externally measured changes in primary and nodal tumor size on intraoral examination from baseline to time of surgery, as assessed by cross-sectional measurement of tumors/ulceration with calipers during dental exam. (Phase IIa [dose expansion, Group 2])
III. To evaluate clinical changes in periodontal condition on dental examination over the study period, as assessed according to the American Academy of Periodontology grading system. (Phase IIa [dose expansion, Group 2])
EXPLORATORY OBJECTIVES:
I. To characterize nisin-induced changes in oral microbiome population structure and function, and nisin sensitivity among key oral bacterial species. (Phase I [dose finding, Group 1] and Phase IIa [dose expansion, Group 2] who are treated with the maximum tolerated dose [MTD]/recommended phase 2 dose [RP2D] of nisin)
II. To characterize inflammatory and antitumor cellular responses to nisin in the oral cancer environment. (Phase I [dose finding, Group 1] and Phase IIa [dose expansion, Group 2] who are treated with the MTD/RP2D of nisin)
III. To confirm the half-life and urinary excretion profile on nisin. (Phase I [dose finding, Group 1])
IV. To demonstrate the preliminary efficacy of nisin administration, as assessed by relapse-free survival (RFS) and overall survival (OS). (Phase IIa [dose expansion, Group 2])
OUTLINE: This is a phase I dose-escalation study of nisin followed by a phase IIa dose expansion study.
Patients receive nisin orally (PO) once daily (QD) or every other day (QOD) starting 2 weeks prior to planned surgical resection. Nisin is temporarily withheld at the time of surgery while patient is under inpatient care on trial. Treatment continues for up to 6 months after surgery in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor tissue sample collection during screening and during surgery.
Upon completion of study treatment, patients are followed up at 30 days, 9 months, and 12 months after surgery.
Lead OrganizationUniversity of California San Francisco
Principal InvestigatorSue Sun Yom
