NisinZ® P for Oral Cancer

Overseen By Angie Valadez

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Francisco

Must not be taking: Antibiotics, Anticancer therapy

Disqualifiers: HPV positive, Oropharyngeal cancer, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on long-term antibiotics or systemic anticancer therapy, you may need to discuss this with the study team.

Is NisinZ® P safe for use in humans?

NisinZ® P has been used safely in humans for many years as a food preservative, and studies show that it does not cause harm to organs or lead to inflammation, fibrosis (thickening and scarring of tissue), or necrosis (tissue death) in treated mice. ^{1 2 3 4 5}

Research Team

Sue S. Yom

Principal Investigator

University of California, San Francisco

Yvonne Kapila, MD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

This trial is for adults with non-metastatic oral cavity squamous cell carcinoma (OSCC) who are undergoing surgery at UCSF. Participants must have confirmed OSCC, be able to consent, and not have distant metastases or a history of certain other cancers. They should not have untreated major dental issues or allergies to nisin.

Inclusion Criteria

I have at least two of my own teeth.

My surgery and follow-up treatment will follow my usual care plan, not changed by this study.

I am 18 years old or older.

Exclusion Criteria

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

I am undergoing major dental surgery as part of my long-term treatment.

Individuals with a known history of hypersensitivity reactions or oral allergies to nisin, any of its excipients, or any related food preservatives

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase I

Participants receive oral nisin once daily starting two weeks before planned OSCC resection surgery and continue for 6 additional months post-surgery. Nisin is withheld during surgery.

6 months

Regular visits for monitoring adverse events and dose adjustments

Treatment Phase IIa

Participants continue receiving oral nisin at the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) for 6 months post-surgery.

6 months

Regular visits for monitoring treatment completion and safety

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of periodontal conditions and adverse events.

12 months

Periodic follow-up visits

Treatment Details

Interventions

• NisinZ® P
• Surgery

Trial Overview The study tests the effects of an oral compound called NisinZ® P in patients with OSCC alongside their standard surgical treatment. It aims to see if NisinZ® P can improve outcomes when used as part of routine care that may include radiation/chemoradiation post-surgery.

Participant Groups

Group I: Phase IIa, Dose Expansion (MTD/RP2D) Experimental Treatment 2 Interventions

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.

Group II: Phase I, Dose Finding - Starting Dose (20,000 mg) Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Nisin ZP, a high-content variant of the antimicrobial peptide nisin, shows greater antitumor effects in head and neck squamous cell carcinoma (HNSCC) compared to low-content nisin, inducing significant apoptosis in cancer cells and reducing tumor growth in vivo.

The treatment with nisin ZP was safe, as it did not cause inflammation or damage to normal organs, and it extended survival in treated mice, highlighting its potential as a novel therapeutic option for HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nisin ZP, a Bacteriocin and Food Preservative, Inhibits Head and Neck Cancer Tumorigenesis and Prolongs Survival. Kamarajan, P., Hayami, T., Matte, B., et al.[2022]

In a study of 619 patients undergoing neck dissection for head and neck cancer, 22.9% experienced adverse events within 30 days, highlighting the need for careful monitoring post-surgery.

Key risk factors for these adverse events included dyspnea, previous cardiac surgery, longer anesthesia times, and higher total work relative value units, which can help guide preoperative assessments and patient counseling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of adverse events after neck dissection: An analysis of the 2006-2011 National Surgical Quality Improvement Program (NSQIP) Database. Jain, U., Somerville, J., Saha, S., et al.[2019]

A risk map was developed in the Oral and Maxillofacial Surgery Service at the University Hospital 'Virgen de las Nieves' to identify and minimize adverse effects (AEs), with 33 AEs identified during the study period from June 2017 to May 2018.

The study found that the Surgical Area had a higher incidence of AEs (22) compared to Outpatient Clinic and Hospital Discharge areas (6), highlighting the need for targeted safety measures in surgical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of a risk map in an oral and maxillofacial surgical unit]. Sánchez López, JD., Cambil Martín, J., Villegas Calvo, M., et al.[2020]

In a study of 1,270 patients undergoing visceral surgery, the novel ClassIntra classification system effectively correlated higher grades of intraoperative adverse events (iAEs) with increased severity of postoperative complications, indicating its potential as a predictive tool for patient outcomes.

Patients with higher ClassIntra grades experienced longer postoperative hospital stays and more complications, demonstrating that this classification can help identify patients at greater risk for adverse outcomes after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Classification of intraoperative adverse events in visceral surgery. Gawria, L., Rosenthal, R., van Goor, H., et al.[2023]

ClassIntra version 1.0 is a newly validated classification system for assessing intraoperative adverse events, demonstrating a clear link between the severity of these events and subsequent postoperative complications in a study of 2520 surgical patients.

The study found that 24% of patients experienced intraoperative adverse events, and the ClassIntra system showed high criterion validity with an intraclass correlation coefficient of 0.76, indicating it can reliably assess complications and could be integrated into routine surgical safety practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective validation of classification of intraoperative adverse events (ClassIntra): international, multicentre cohort study. Dell-Kuster, S., Gomes, NV., Gawria, L., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Nisin ZP, a Bacteriocin and Food Preservative, Inhibits Head and Neck Cancer Tumorigenesis and Prolongs Survival. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Predictors of adverse events after neck dissection: An analysis of the 2006-2011 National Surgical Quality Improvement Program (NSQIP) Database. [2019]

3. Spain pubmed.ncbi.nlm.nih.gov

[Development of a risk map in an oral and maxillofacial surgical unit]. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Classification of intraoperative adverse events in visceral surgery. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Prospective validation of classification of intraoperative adverse events (ClassIntra): international, multicentre cohort study. [2022]