Study Evaluating The Role of ClO2 on Mucositis for Pt. Undergoing Head/Neck Radiotherapy

A Pilot Phase II Study Evaluating the Role of Chlorine Dioxide on Mucositis for Patients Undergoing Head and Neck Radiotherapy

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03602066

Enrollment

Registered

2018-07-26

Start date

2019-02-14

Completion date

2022-11-07

Last updated

2024-03-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Head and Neck Carcinoma

Brief summary

This pilot randomized phase II trial studies who well chlorine dioxide sterilization works in reducing oral mucositis in patients with stage I-IV head and neck cancer who are undergoing radiotherapy. Chlorine dioxide sterilization may help to treat oral mucositis.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate and compare CloSYS Unflavored Oral Rinse effect on the incidence of severe oral oral mucositis (OM) (\>= World Health Organization \[WHO\] grade 3). SECONDARY OBJECTIVES: I. To evaluate and compare CloSYS Unflavored Oral Rinse effect on the time to onset of severe OM (\>= WHO grade 3). II. To evaluate and compare CloSYS Unflavored Oral Rinse effect on the duration of severe OM (\>= WHO grade 3). III. To evaluate and compare CloSYS Unflavored Oral Rinse effect in patient reported outcomes as measured by the Oral Mucositis Weekly Questionnaire (OMWQ). IV. To evaluate and compare CloSYS Unflavored Oral Rinse effect on rates of radiation therapy (RT) interruption. V. To evaluate and compare CloSYS Unflavored Oral Rinse effect on the oral microbiome. VI. To evaluate and compare CloSYS Unflavored Oral Rinse effect on salivary TNFalpha, IL-1beta, and IL-6 levels. OUTLINE: Patients are randomized into 1 of 2 arms. ARM I: Patients receive chlorine dioxide sterilization oral rinse over 30 seconds twice daily (BID) from the start of radiation therapy (RT) to the evening prior to the 1 month RT follow-up appointment. ARM II: Patients receive placebo oral rinse over 30 seconds BID from the start of RT to the evening prior to the 1 month RT follow-up appointment. After completion of study, patients are followed up on day 1.

Interventions

DRUGChlorine Dioxide Sterilization

Given via oral rinse

OTHERLaboratory Biomarker Analysis

Correlative studies

OTHERPlacebo

Given via oral rinse

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Able to provide properly obtained written informed consent * Pathologically-confirmed diagnosis of head and neck malignancy (stage I-IV) * Planned to receive high dose RT \>= 50 gray (Gy) to visualizable oral cavity and/or oropharyngeal mucosa, with or without administration of concurrent systemic therapy * Karnofsky performance status of \>= 60, within 45 days of registration * Hematocrit (Hct) \> 20 within 90 days of registration to the study * Normal cognition and willingness to complete OMWQ and Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTAE) forms at each designated time point along with oral rinse diary * Life expectancy \>= 3 months * Willing to tolerate oral rinsing for 30 second intervals * Negative serum pregnancy test in females of childbearing age * Must be willing to use an effective form of birth control if of child bearing potential

Exclusion criteria

* Known hypersensitivity to chlorine dioxide products * Chlorine dioxide product usage within the past 7 days prior to registration for this study * Utilization of any antibiotic medications (topical or systemic) within past 7 days prior to registration for this study * Utilization of daily anti-inflammatory or corticosteroid medication (topical or systemic) for chronic indication other than daily low dose aspirin (81 mg) * Sjogrens disease * Medically documented glucose-6-phosphate dehydrogenase (G6PD) deficiency * Baseline hematocrit =\< 20% * Planned daily RT of less than 5 weeks duration * Known history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) * Current pregnancy

Design outcomes

Primary

Measure	Time frame	Description
Incidence of Severe Oral Mucositis (OM) (>= World Health Organization [WHO] Mucositis Scale Grade 3)	Up to 30 days post radiotherapy	Will be compared between arms. Analysis will be performed by estimating the proportion with exact 95% binomial confidence interval for each group separately. Statistical testing will use a chi-square test. As an alternative, Fisher?s Exact Test will be used if the minimum expected value is \< 5. WHO Scale: Grade 0 (none) - None; Grade I (mild) - Oral soreness, erythema; Grade II (moderate) - Oral erythema, ulcers, solid diet tolerated; Grade III (severe) - Oral ulcers, liquid diet only; Grade IV (life-threatening) - Oral alimentation impossible. No grade 3 or higher Oral Mucositis was reported on either treatment arm, so no differences were observed.

Secondary

Measure	Time frame	Description
Time to Onset of Severe OM (>= World Health Organization [WHO] Mucositis Scale Grade 3)	Up to 30 days post radiotherapy	Will be tabulated and the median week to onset will be computed for each group. Comparison will be performed using a Wilcoxon Rank Sum Test (as the values are unlikely to be normally distributed).
Duration of Severe OM (>= World Health Organization [WHO] Mucositis Scale Grade 3)	Up to 30 days post radiotherapy	will be tabulated and the median week to onset will be computed for each group. Comparison will be performed using a Wilcoxon Rank Sum Test (as the values are unlikely to be normally distributed).
Patient Reported Outcomes as Measured by the Oral Mucositis Weekly Questionnaire (OMWQ)	Up to 30 days post radiotherapy	Will be compared between groups using a linear mixed-effects model to account for the correlation among the measurements within an individual.
Rates of Radiotherapy Interruption	Up to 30 days post radiotherapy	Will be tabulated and compared using a chi-square test.

Other

Measure	Time frame	Description
Oral Microbiome	Up to 30 days post radiotherapy	Will be compared between groups using a linear mixed-effects model to account for the correlation among the measurements within an individual.
Salivary TNFalpha, IL-1beta, and IL-6 Levels	Up to 30 days post radiotherapy	Will be compared between groups using a linear mixed-effects model to account for the correlation among the measurements within an individual.

Countries

United States

Participant flow

Recruitment details

The study opened on 02/14/2019 and 8 subjects were accrued between February 2019 and November 2019. A subject discovered mold in the IP and all IP was returned to manufacturer and the 8 subjects were withdrawn from study. The study closed to accrual and re-opened 01/15/2022. Subjects were recruited from the University of Arizona Cancer Center clinic from 01/15/2022-08/24/2022. The study closed prematurely as the drug manufacturer pulled funding and IP. Enrolled = 14

Participants by arm

Arm	Count
Arm I (Chlorine Dioxide Sterilization) Patients receive chlorine dioxide sterilization oral rinse over 30 seconds BID from the start of RT to the evening prior to the 1 month RT follow-up appointment. Chlorine Dioxide Sterilization: Given via oral rinse Laboratory Biomarker Analysis: Correlative studies	6
Arm II (Placebo) Patients receive placebo oral rinse over 30 seconds BID from the start of RT to the evening prior to the 1 month RT follow-up appointment. Laboratory Biomarker Analysis: Correlative studies Placebo: Given via oral rinse	8
Total	14

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Physician Decision	1	0
Overall Study	Withdrawal by Subject	2	0

Baseline characteristics

Characteristic	Arm I (Chlorine Dioxide Sterilization)	Arm II (Placebo)	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	3 Participants	3 Participants	6 Participants
Age, Categorical Between 18 and 65 years	3 Participants	5 Participants	8 Participants
Age, Continuous	61.5 years	64 years	61.5 years
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	1 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants	7 Participants	13 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
General dental condition Excellent	4 Participants	3 Participants	7 Participants
General dental condition Fair	1 Participants	1 Participants	2 Participants
General dental condition Good	1 Participants	4 Participants	5 Participants
HNC staging Stage I	3 Participants	4 Participants	7 Participants
HNC staging Stage II	0 Participants	1 Participants	1 Participants
HNC staging Stage III	2 Participants	2 Participants	4 Participants
HNC staging Stage IV	1 Participants	1 Participants	2 Participants
Karnofsky Performance Score	90 Score on a scale	90 Score on a scale	90 Score on a scale
Number of teeth	22 teeth	28.5 teeth	25 teeth
Oral Mucositis (OM) Grade 0 (none)	6 Participants	7 Participants	13 Participants
Oral Mucositis (OM) Grade 1 (mild)	0 Participants	1 Participants	1 Participants
Oral Mucositis (OM) Grade 2 (moderate)	0 Participants	0 Participants	0 Participants
Oral Mucositis (OM) Grade 3 (severe)	0 Participants	0 Participants	0 Participants
Oral Mucositis (OM) Grade 4 (life-threatening)	0 Participants	0 Participants	0 Participants
Oral Mucositis (OM) Grade Unknown	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) White	5 Participants	6 Participants	11 Participants
Region of Enrollment United States	6 participants	8 participants	14 participants
Sex: Female, Male Female	1 Participants	2 Participants	3 Participants
Sex: Female, Male Male	5 Participants	6 Participants	11 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 6	0 / 8
other Total, other adverse events	6 / 6	8 / 8
serious Total, serious adverse events	0 / 6	1 / 8

Outcome results

Primary

Incidence of Severe Oral Mucositis (OM) (>= World Health Organization [WHO] Mucositis Scale Grade 3)

Will be compared between arms. Analysis will be performed by estimating the proportion with exact 95% binomial confidence interval for each group separately. Statistical testing will use a chi-square test. As an alternative, Fisher?s Exact Test will be used if the minimum expected value is \< 5. WHO Scale: Grade 0 (none) - None; Grade I (mild) - Oral soreness, erythema; Grade II (moderate) - Oral erythema, ulcers, solid diet tolerated; Grade III (severe) - Oral ulcers, liquid diet only; Grade IV (life-threatening) - Oral alimentation impossible. No grade 3 or higher Oral Mucositis was reported on either treatment arm, so no differences were observed.