Trial Title:
Nisin in Oral Cavity Squamous Cell Carcinoma (OCSCC)
NCT ID:
NCT06097468
Condition:
Oral Cavity Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Nisin
Nisin Z
Conditions: Keywords:
Oral Microbiome
Natural Food Preservative
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
NisinZ® P
Description:
NisinZ® P is an ultrapure Nisin Z concentrate produced by fermentation using the
bacterium Lactococcus lactis obtained from sauerkraut
Arm group label:
Phase I, Dose Finding - Starting Dose (20,000 mg)
Arm group label:
Phase IIa, Dose Expansion (MTD/RP2D)
Other name:
Nisin Z
Other name:
Nisin Z concentrate
Other name:
Ultrapure Nisin Z concentrate
Intervention type:
Procedure
Intervention name:
Surgery (non-interventional, standard of care)
Description:
Surgical removal of tumor as part of standard of care treatment
Arm group label:
Phase I, Dose Finding - Starting Dose (20,000 mg)
Arm group label:
Phase IIa, Dose Expansion (MTD/RP2D)
Other name:
Surgical resection
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.
Criteria for 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. Concurrent systemic anticancer therapy or chemoradiation is permitted
after enrollment.
8. Individuals currently receiving any other investigational agent or using an
investigational device intended as anticancer therapy.
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California, San Francisco
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Recruiting
Contact:
Last name:
Angelica Valadez
Phone:
415-502-1879
Email:
Angelica.Valadez@ucsf.edu
Contact backup:
Phone:
877-827-3222
Email:
cancertrials@ucsf.edu
Investigator:
Last name:
Sue Yom, MD
Email:
Principal Investigator
Start date:
February 2, 2024
Completion date:
September 1, 2027
Lead sponsor:
Agency:
University of California, San Francisco
Agency class:
Other
Collaborator:
Agency:
University of California, Los Angeles
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
University of California, San Francisco
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06097468
