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Nisin in Oral Cavity Squamous Cell Carcinoma (OCSCC)

Primary Purpose

Oral Cavity Squamous Cell Carcinoma

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NisinZ® P
Surgery (non-interventional, standard of care)
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oral Cavity Squamous Cell Carcinoma focused on measuring Oral Microbiome, Natural Food Preservative

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histological or cytological confirmation of oral cavity squamous cell carcinoma (OSCC). 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. Exclusion Criteria: 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. Concurrent systemic anticancer therapy or chemoradiation is permitted after enrollment. Individuals currently receiving any other investigational agent or using an investigational device intended as anticancer therapy. 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.

Sites / Locations

  • University of California, San Francisco

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

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

Phase IIa, Dose Expansion (MTD/RP2D)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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
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.
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.

Secondary Outcome Measures

Incidence of Treatment-emergent adverse events (AE)
Safety will be assessed by monitoring adverse events (AEs), including Grade >=3 intraoral mucositis. AEs will be graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. AEs will be evaluated up to 60 days after treatment discontinuation.
Mean change in dimensional measurement of ulcerations over time
Mean change in cross-sectional, dimensional measurement of tumors/ulcerations from baseline to post-surgery will be measured with calipers during a dental exam and reported by cohort.
Proportion of participants with changes in periodontal pocket depth
Clinical changes in periodontal pocket depth on dental examination over the study period will be assessed according to the American Academy of Periodontology grading system.
Proportion of participants with changes in periodontal clinical detachment loss
Clinical changes in clinical detachment loss on dental examination over the study period will be assessed according to the American Academy of Periodontology grading system.
Proportion of participants with changes in periodontal bleeding
Clinical changes in bleeding upon probing at 6 sites per tooth on dental examination over the study period will be assessed according to the American Academy of Periodontology grading system.

Full Information

First Posted
October 18, 2023
Last Updated
October 18, 2023
Sponsor
University of California, San Francisco
Collaborators
University of California, Los Angeles, National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT06097468
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 1, 2024 (Anticipated)
Primary Completion Date
July 1, 2027 (Anticipated)
Study Completion Date
September 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
University of California, Los Angeles, National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oral Cavity Squamous Cell Carcinoma
Keywords
Oral Microbiome, Natural Food Preservative

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase I, Dose Finding - Starting Dose (20,000 mg)
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase IIa, Dose Expansion (MTD/RP2D)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
NisinZ® P
Other Intervention Name(s)
Nisin Z, Nisin Z concentrate, Ultrapure Nisin Z concentrate
Intervention Description
NisinZ® P is an ultrapure Nisin Z concentrate produced by fermentation using the bacterium Lactococcus lactis obtained from sauerkraut
Intervention Type
Procedure
Intervention Name(s)
Surgery (non-interventional, standard of care)
Other Intervention Name(s)
Surgical resection
Intervention Description
Surgical removal of tumor as part of standard of care treatment
Primary Outcome Measure Information:
Title
Proportion of participants with dose limiting toxicities (DLT) (Phase I)
Description
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
Time Frame
Up to 6 months
Title
Maximum Tolerated Dose / Recommended Phase II Dose (RP2D) (Phase I)
Description
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.
Time Frame
Up to 4 weeks
Title
Proportion of participants completing treatment (Phase II)
Description
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.
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Incidence of Treatment-emergent adverse events (AE)
Description
Safety will be assessed by monitoring adverse events (AEs), including Grade >=3 intraoral mucositis. AEs will be graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. AEs will be evaluated up to 60 days after treatment discontinuation.
Time Frame
Up to 8 months
Title
Mean change in dimensional measurement of ulcerations over time
Description
Mean change in cross-sectional, dimensional measurement of tumors/ulcerations from baseline to post-surgery will be measured with calipers during a dental exam and reported by cohort.
Time Frame
Up to 6 months
Title
Proportion of participants with changes in periodontal pocket depth
Description
Clinical changes in periodontal pocket depth on dental examination over the study period will be assessed according to the American Academy of Periodontology grading system.
Time Frame
Up to 6 months
Title
Proportion of participants with changes in periodontal clinical detachment loss
Description
Clinical changes in clinical detachment loss on dental examination over the study period will be assessed according to the American Academy of Periodontology grading system.
Time Frame
Up to 6 months
Title
Proportion of participants with changes in periodontal bleeding
Description
Clinical changes in bleeding upon probing at 6 sites per tooth on dental examination over the study period will be assessed according to the American Academy of Periodontology grading system.
Time Frame
Up to 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histological or cytological confirmation of oral cavity squamous cell carcinoma (OSCC). 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. Exclusion Criteria: 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. Concurrent systemic anticancer therapy or chemoradiation is permitted after enrollment. Individuals currently receiving any other investigational agent or using an investigational device intended as anticancer therapy. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Angelica Valadez
Phone
415-502-1879
Email
Angelica.Valadez@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sue Yom, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yvonne Kapila, MD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angelica Valadez
Phone
415-502-1879
Email
Angelica.Valadez@ucsf.edu
Phone
877-827-3222
Email
cancertrials@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Sue Yom, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Nisin in Oral Cavity Squamous Cell Carcinoma (OCSCC)

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