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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an oral treatment called NisinZ® P for individuals with oral cavity squamous cell carcinoma (OSCC). The researchers aim to determine if taking Nisin before and after surgery can improve outcomes for those undergoing surgery and possibly radiation or chemoradiation. Participants will take the treatment daily, starting two weeks before their cancer surgery and continuing for six months afterward. Suitable candidates have a confirmed OSCC diagnosis with a tumor size of at least 2 cm, plan to have surgery at UCSF, and have at least two teeth for study purposes. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nisin, the main ingredient in NisinZ® P, is generally safe for humans. Nisin, a protein produced by bacteria, has FDA approval as a food preservative due to its effectiveness against harmful bacteria. It has been used in foods for years without major safety concerns.

Past studies where participants took nisin orally found it remained in the body for several hours, indicating natural processing and elimination. These studies reported no major side effects. However, the trial under consideration is in its early stages, so researchers are closely monitoring safety. This phase focuses on determining the safe dosage, with careful monitoring and management of any side effects or issues.

By joining this study, participants will help researchers learn more about nisin's effectiveness and safety in treating oral cancer, especially when combined with surgery and possibly radiation treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for oral cancer?

Unlike the standard treatments for oral cancer, which often involve surgery followed by radiation or chemotherapy, NisinZ® P is derived from a naturally occurring antimicrobial peptide called nisin. This treatment is unique because it is administered orally and may enhance the effects of surgery and other therapies by continuing to work over six months post-surgery. Researchers are excited about NisinZ® P because it offers a novel mechanism of action that targets cancer cells in a way that traditional treatments do not, potentially improving outcomes and reducing the need for more aggressive interventions.

What evidence suggests that NisinZ® P might be an effective treatment for oral cancer?

Research has shown that nisin may help reduce the size of oral cancer tumors, based on animal studies. In mice, nisin not only reduced tumor size but also extended their lifespan. Another study suggested that nisin can help maintain a healthy balance of bacteria in the mouth, potentially preventing harmful bacteria from dominating. These findings indicate that nisin could complement traditional oral cancer treatments. In this trial, participants will receive NisinZ® P alongside surgery to evaluate its potential benefits. Although more research is needed to confirm these effects in humans, the early results are promising. ^{1 2 6 7 8}

Who Is on the Research Team?

Sue S. Yom

Principal Investigator

University of California, San Francisco

Yvonne Kapila, MD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

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.

My cancer is confirmed as squamous cell carcinoma in the mouth.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06097468

Nisin in Oral Cavity Squamous Cell Carcinoma (OCSCC) This is a study of oral nisin administration in patients with OSCC who are undergoing complete surgical resection surgery with or without adjuvant radiation/ ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06097468?cond=Squamous%20Cell%20Carcinoma%20oral%20cavity&aggFilters=status:rec%20not&rank=1

Nisin in Oral Cavity Squamous Cell Carcinoma (OCSCC) This is a study of oral nisin administration in patients with OSCC who are undergoing complete surgical resection surgery with or without adjuvant ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7482728/

Modulation of pathogenic oral biofilms towards health with ... Our data indicate that a nisin probiotic and/or nisin can reduce the levels of these pathogens down to control levels, while promoting commensal bacteria, such ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-08852

Evaluating the Effect of Nisin on the Oral Microbiome ... 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 ...

5. dentistry.ucla.edu dentistry.ucla.edu/news-article/have-cheese-chasing-mice-unlocked-a-new-oral-cancer

New Oral Cancer Remedy Research led by Dr. Yvonne Hernandez-Kapila has shown that nisin reduced the size of oral cancer tumors in mice and prolonged their survival.

6. sciencedirect.com sciencedirect.com/science/article/pii/S1756464623001597

Nisin and its application in oral diseases Nisin A is the only bacteriocin approved by the FDA as a food biopreservative. Nisin shows great antimicrobial ability and has been used against oral pathogens.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12439769/

Case of Nisin Oral Ingestion and its LC-MS/MS Detection in ... Mass spectrometry data revealed that nisin was detected in urine samples 4–20 hours after the first ingestion and up to 14 hours after the second ingestion, ...

8. handary.com handary.com/product-show-NisinZ_P-Ultrapure-Nisin-Z

NisinZ® P - Ultrapure Nisin Z NisinZ P is an ultrapure Nisin Z produced through fermentation using the bacterium Lactococcus lactis sourced from sauerkraut.