Clinical trial NCT06097468: Nisin in Oral Cavity Squamous Cell Carcinoma (OCSCC)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Oral Cavity Squamous Cell Carcinoma
Keywords: Oral Microbiome
Natural Food Preservative
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
name: National Cancer Institute (NCI)
First posted: 2023-10-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

1. Participants with a suspected clinical diagnosis of oral cavity squamous cell carcinoma (OSCC) who are planning to undergo a diagnostic biopsy. Note: Subsequent documentation from the medical record (e.g., from the diagnostic biopsy pathology report) of histological or cytological confirmation of OSCC is required prior to enrollment and treatment on study. Participants who do not have a histological/cytological confirmation of OSCC, or who are unable to provide sufficient volume of biopsy tissue for research, will not be eligible to enroll in the study.
2. OSCC mass must be \>= 2cm in size.
3. Non-metastatic OSCC (no distant metastases allowed; metastasis to the neck is eligible).
4. Participants must be planning for a complete OSCC surgical resection, with or without adjuvant radiation/chemoradiation, at UCSF, as part of their routine treatment plan. Surgical resection and adjuvant treatment will be according to the participants routine or standard of care treatment plan and will not be dictated by the study (non-interventional).
5. Age \>= 18 years
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Karnofsky ≥ 50%).
7. Participants must be dentate (retaining at least two teeth). Teeth are required for plaque sample collection for correlative studies.
8. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

1. Individuals with a history of a known positive human papillomavirus deoxyribonucleic acid ((HPV DNA) test (P16-positive is permitted if HPV DNA test is negative).
2. Individuals with a history of or concurrent oropharyngeal, laryngeal, or hypopharyngeal cancers (other than OSCC). Individuals with any other prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or endpoints of this study are eligible.
3. Individuals with ongoing uncorrected oral pathology, which in the opinion of the investigator could interfere with the safety or endpoints of this study or could be exacerbated during the course of study participation, if left untreated. These conditions may be discussed with the study PI to determine eligibility.

   * Current and ongoing long-term dental treatment requiring major surgery;
   * Untreated carious lesions, severe oral infections, or known defective restorations;
   * Other suspicious uncorrected oral pathology.
4. Individuals with a known history of hypersensitivity reactions or oral allergies to nisin, any of its excipients, or any related food preservatives.
5. Individuals with complete inability to absorb nutrients via gastrointestinal tract due to major medical disorder or history of gastrointestinal surgical removal.
6. Individuals who have received extended (\>4 weeks) antibiotic therapy within 1 month of the baseline visit or who currently require continuous antibiotic prophylaxis at the time of enrollment.
7. Individuals who require treatment with a systemic anticancer therapy prior to enrollment, with the exception of prior immunotherapy which is permitted both prior to enrollment and concurrent with study participation.
8. Individuals currently receiving any other investigational agent or using an investigational device intended as anticancer therapy, with the exception of investigational immunotherapy, which is permitted both prior to enrollment and concurrent with study participation.
9. Individuals with ongoing Grade 2 events that are not clinically stable or ongoing \>= Grade 3 events (CTCAE v5.0 grading).
10. Individuals with any condition or social circumstance that, in the opinion of the investigator, would impair the participant's ability to comply with study activities, interfere with participant safety, or study endpoints.

Primary outcomes:
measure: Proportion of participants with dose limiting toxicities (DLT) (Phase I)
timeFrame: Up to 6 months
measure: Maximum Tolerated Dose / Recommended Phase II Dose (RP2D) (Phase I)
timeFrame: Up to 4 weeks
measure: Proportion of participants completing treatment (Phase II)
timeFrame: Up to 6 months
Secondary outcomes:
measure: Incidence of Treatment-emergent adverse events (AE)
timeFrame: Up to 8 months
measure: Mean change in dimensional measurement of ulcerations over time
timeFrame: Up to 6 months
measure: Proportion of participants with changes in periodontal pocket depth
timeFrame: Up to 6 months
measure: Proportion of participants with changes in periodontal clinical detachment loss
timeFrame: Up to 6 months
measure: Proportion of participants with changes in periodontal bleeding
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Sue Yom, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Yvonne Kapila, MD
role: PRINCIPAL_INVESTIGATOR
References: