Nisin in Oral Cavity Squamous Cell Carcinoma (OCSCC)

NCT06097468 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 23203NCI-2023-08852R01CA269950-04
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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).

Conditions

Oral Cavity Squamous Cell Carcinoma

Keywords

Oral Microbiome; Natural Food Preservative

Outcome Measures

Primary Outcomes (3)

• 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

  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.

  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.

  Up to 6 months

Secondary Outcomes (5)

• Incidence of Treatment-emergent adverse events (AE)

  Up to 8 months

• Mean change in dimensional measurement of ulcerations over time

  Up to 6 months

• Proportion of participants with changes in periodontal pocket depth

  Up to 6 months

• Proportion of participants with changes in periodontal clinical detachment loss

  Up to 6 months

• Proportion of participants with changes in periodontal bleeding

  Up to 6 months

Study Arms (2)

Phase I, Dose Finding - Starting Dose (20,000 mg)

EXPERIMENTAL

Participants will ingest oral nisin once daily starting two weeks before planned complete OSCC resection surgery and will continue once daily administration for 6 additional months post-surgery (concurrent with adjuvant radiation/chemoradiation, for participants whose routine treatment plan includes adjuvant therapy). Nisin will be temporarily withheld at the time of OSCC resection surgery while the participant is under inpatient care. The starting dose level, with dose modification permitted for toxicity management or intolerability will be 20,000 mg (2 x 10 g bottles) per day.

Drug: NisinZ® P; Procedure: Surgery (non-interventional, standard of care)

Phase IIa, Dose Expansion (MTD/RP2D)

EXPERIMENTAL

Participants will ingest oral nisin once daily starting two weeks before planned complete OSCC resection surgery and will continue once daily administration for 6 additional months post-surgery (concurrent with adjuvant radiation/chemoradiation, for participants whose routine treatment plan includes adjuvant therapy). Nisin will be temporarily withheld at the time of OSCC resection surgery while the participant is under inpatient care. The dose level will be determined by the outcomes in Phase 1 (RP2D), with dose modification permitted for toxicity management or intolerability.

Drug: NisinZ® P; Procedure: Surgery (non-interventional, standard of care)

Interventions

NisinZ® P DRUG

NisinZ® P is an ultrapure Nisin Z concentrate produced by fermentation using the bacterium Lactococcus lactis obtained from sauerkraut

Also known as: Nisin Z, Nisin Z concentrate, Ultrapure Nisin Z concentrate

Phase I, Dose Finding - Starting Dose (20,000 mg); Phase IIa, Dose Expansion (MTD/RP2D)

Surgery (non-interventional, standard of care) PROCEDURE

Surgical removal of tumor as part of standard of care treatment

Also known as: Surgical resection

Phase I, Dose Finding - Starting Dose (20,000 mg); Phase IIa, Dose Expansion (MTD/RP2D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• OSCC mass must be \>= 2cm in size.
• Non-metastatic OSCC (no distant metastases allowed; metastasis to the neck is eligible).
• 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).
• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Karnofsky ≥ 50%).
• Participants must be dentate (retaining at least two teeth). Teeth are required for plaque sample collection for correlative studies.
• Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• 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).
• 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.
• 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.
• Individuals with a known history of hypersensitivity reactions or oral allergies to nisin, any of its excipients, or any related food preservatives.
• Individuals with complete inability to absorb nutrients via gastrointestinal tract due to major medical disorder or history of gastrointestinal surgical removal.
• 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.
• 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.
• 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.
• Individuals with ongoing Grade 2 events that are not clinically stable or ongoing \>= Grade 3 events (CTCAE v5.0 grading).
• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Cancer Institute (NCI): collaborator
• University of California, Los Angeles: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

nisin Z; Surgical Procedures, Operative; Standard of Care

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Sue Yom, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Yvonne Kapila, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Narimane Badawi

CONTACT

(415) 866-7594; Narimane.Badawi@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: October 24, 2023
• Study Start: February 2, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)