A Phase I/IIa, Single-Arm, Dose-Confirmation and Dose-Expansion Study Evaluating Changes in the Oral Microbiome of Patients With Oral Cavity Squamous Cell Carcinoma (OSCC) After Short-Term Ingestion of Nisin, a Naturally Occurring Food Preservative
Summary
This is a study of oral nisin administration in patients with OSCC who are undergoing complete surgical resection surgery with or without adjuvant radiation/chemoradiation as part of their routine care at the University of California, San Francisco (UCSF).
Detailed description
PRIMARY OBJECTIVES: I. To demonstrate the tolerability of nisin administration, as assessed by the maximum tolerated dose (MTD) of nisin (Phase I). II. To demonstrate the feasibility of nisin administration, as assessed by the treatment completion rate (Phase IIa). SECONDARY OBJECTIVES: I. To evaluate the safety of nisin administration, as assessed by the frequency and severity of adverse events (CTCAE v5.0) (Phase I). 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). 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). EXPLORATORY OBJECTIVES: I. To characterize nisin-induced changes in oral microbiome population structure and function, and nisin sensitivity among key oral bacterial species. II. To characterize inflammatory and anti-tumor cellular responses to nisin in the oral cancer environment. III. To confirm the half-life and urinary excretion profile of nisin (Phase 1). IV. To demonstrate the preliminary efficacy of nisin administration, as assessed by relapse-free survival (RFS) and overall survival (OS) (Phase IIa). OUTLINE: Participants receiving treatment at UCSF will be initially assigned to the Phase 1 dose finding arm. After an interim analysis is completed, enrollment into Phase IIa will begin at the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Participants will be treated for two weeks before planned surgery, complete OSCC resection surgery (standard of care, non-interventional) and will continue treatment for 6 additional months post-surgery. Follow-up will continue for 12 months after surgery.
Arms & interventions
- DrugNisinZ® P
NisinZ® P is an ultrapure Nisin Z concentrate produced by fermentation using the bacterium Lactococcus lactis obtained from sauerkraut
- ProcedureSurgery (non-interventional, standard of care)
Surgical removal of tumor as part of standard of care treatment
Outcome measures
Primary
Proportion of participants with dose limiting toxicities (DLT) (Phase I)
Dose-limiting toxicities (DLTs) are defined in Section 5.2.3. DLT determination will assess adverse events (AEs) graded according to CTCAE v5.0, including findings on physical exam, vital signs, laboratory testing, and spontaneous reports of AEs reported to the investigator by participants. DLT data will be summarized as proportions of participants experiencing DLTs per cohort
Time frame: Up to 6 months
Maximum Tolerated Dose / Recommended Phase II Dose (RP2D) (Phase I)
The maximum tolerated dose (MTD) is the highest dose at which no more than one instance of DLT is observed among 6 participants treated. The MTD from Phase I will be the recommended Phase IIa dose (RP2D) for use in Phase IIa.
Time frame: Up to 4 weeks
Proportion of participants completing treatment (Phase II)
The treatment completion rate is defined as the proportion of participants allocated to receive nisin at the RP2D and who complete the full nisin regimen, missing fewer than 30% of doses over the course of the regimen. A full nisin regimen is defined as starting nisin 2 weeks before surgery and continuing for 6 months after surgery.
Time frame: Up to 6 months
Secondary
Incidence of Treatment-emergent adverse events (AE)
Time frame: Up to 8 months
Mean change in dimensional measurement of ulcerations over time
Time frame: Up to 6 months
Proportion of participants with changes in periodontal pocket depth
Time frame: Up to 6 months
Proportion of participants with changes in periodontal clinical detachment loss
Time frame: Up to 6 months
Proportion of participants with changes in periodontal bleeding
Time frame: Up to 6 months
Eligibility criteria
Study locations (1)
University of California, San Francisco
San Francisco, California, 94143