Commensal Oral Microbiota in Head and Neck Cancer

Study Overview
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Brief Summary
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The ARMOR Trial will test the efficacy of an oral care protocol to treat oral mucositis (OM) in patients receiving radiation (RT) or chemoradiation (chemoRT) for head and neck cancer. Participants will attend a screening/baseline visit, weekly intervention visits while they are undergoing RT or chemoRT, and a visit 3 months after completing RT or chemoRT. At intervention visits, samples will be collected (such as saliva, oral swabs) and participants will receive their assigned study intervention, either Oral Mucosal Deterging and Dental Prophylaxis protocol (OMDP), which includes a dental cleaning and treatment to the oral mucosa, or a Standard of Care Oral Hygiene, which includes teeth brushing and no treatment to the oral mucosa.

Detailed Description
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This is a prospective, single blind, two arm, randomized, controlled trial to test the efficacy of an oral care protocol to treat oral mucositis (OM) in patients receiving radiation (RT) or chemoradiation (chemoRT) for head and neck cancer. This trial will also measure salivary proinflammatory cytokines, and evaluate other clinical effects of the intervention during cancer therapy. In addition, oral mucosal swabs will be collected for the future characterization of changes in the microbiome associated with OM severity. Patients will be randomized in a 1:1 ratio to two different oral care protocols within 4 strata defined by type of RT (Proton beam therapy (Protons)) vs intensity-modulated radiation therapy (IMRT) and cancer treatment (RT versus chemoRT). Eligible subjects will be assigned to receive either the Oral Mucosal Deterging and Dental Prophylaxis protocol (OMDP) or a Standard of Care Oral Hygiene protocol (SOC-OH). Prior to randomization, all enrolled subjects will receive a baseline dental prophylaxis and fluoride varnish application prior to start of RT or chemoRT to ensure that all subjects enter the study with comparable oral health. Subjects assigned to OMDP will receive the OMDP Protocol (Oral Mucosal Deterging and Dental Prophylaxis) at weekly intervention visits. Subjects randomized to the SOC-OH will receive oral health instructions following the American Dental Association Guidelines and will have their teeth cleaned (brushed) during weekly intervention visits; no treatment to the oral mucosa will be provided to this group. At each bi-weekly study visit, study assessments will include the collection of saliva and oral mucosal swabs, an oral exam and OM assessment, and the completion of questionnaires. During the course of the study, subjects will attend one baseline visit, up to 9 intervention visits, and a follow-up visit approximately 3 months after completion of RT. Local supportive care, including normal saline rinses, topical anesthetics, mixed medication mouthwashes (e.g. Magic Mouthwash), feeding tubes, and pain management will be allowed according to each recruitment site's standard of care procedures.

Official Title
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The ARMOR Trial: Commensal Oral Microbiota as a Trigger of Oral Mucositis Severity

Conditions
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Head and Neck Cancer, Oral Mucositis

Intervention / Treatment
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* Other: Standard of Care Oral Hygiene
* Procedure: Oral mucosal deterging and dental prophylaxis


Participation Criteria
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Eligibility Criteria
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Currently enrolling subjects receiving intensity-modulated radiation therapy (IMRT), with or without chemotherapy. Subject Inclusion Criteria To participate in this study, an individual must meet all the following criteria: 18 years of age or older; Able and willing to provide informed consent prior to initiation of study procedures; Scheduled to undergo radiation or chemoradiation treatment for head/neck cancer; Presents with at least one of nine areas of the oral or oropharyngeal mucosa (i.e., upper lip, lower lip, right cheek, left cheek, right ventral and lateral tongue, left ventral and lateral tongue, floor of the mouth, and soft palate) expected to receive at least 5000 cGy of RT. Patients with cancer located outside of the oral cavity will be included when at least 5000 cGy of RT will be administered to the oral cavity in addition to the RT targeted at the primary cancer site. Presents with a minimum of 6 natural teeth. Subject Exclusion Criteria An individual who meets any of the following criteria will be excluded from participation in this study: Pregnant or lactating at the baseline/screening visit; Participating in another oral health interventional research study at any point during their participation in this trial; Receiving induction chemotherapy or concurrent radiation therapy with cetuximab; Reports current use of antifungal or antibiotic at the time of enrollment; Presents with immunocompromised status (defined as an absolute neutrophil count (ANC) of less than 1000); Presents with any of the following conditions, which based on American Dental and American College of Cardiology guidelines, require antibiotic prophylaxis prior to dental treatment: prosthetic cardiac valves, including transcatheter-implanted prostheses and homografts; prosthetic material used for cardiac valve repair, such as annuloplasty rings and chords; a history of infective endocarditis; a cardiac transplant with valve regurgitation due to a structurally abnormal valve; the following congenital (present from birth) heart disease: unrepaired cyanotic congenital heart disease, including palliative shunts and conduits; or any repaired congenital heart defect with residual shunts or valvular regurgitation at the site of or adjacent to the site of a prosthetic patch or a prosthetic device; Presents with cardiovascular implantable electronic devices (CIEDs) such as pacemakers, and implantable cardioverter-defibrillators; unless, a) in the opinion of the investigator, the OMDP protocol can be performed with hand scalers (and not with an ultrasonic device as per protocol) or upon consult with the treating cardiologist, it is determined that the ultrasonic device can be safely used; Presents with severe periodontal disease for which treatment cannot be completed prior to the start of radiation/chemoradiation (at the discretion of the investigator); Had surgery as part of cancer treatment and is not sufficiently healed to comply with study requirements prior to RT initiation; In the opinion of the investigator, is unable or unlikely to comply fully with the study requirements or procedures for any reason (e.g. cognitive or physical impairment).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, single blind, two arm, randomized, controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Standard of Care Oral Hygiene<br>Standard of Care Oral Hygiene group (SOC-OH): Subjects assigned to SOC-OH will attend weekly oral care visits where they will have their teeth brushed with a soft bristled toothbrush by the interventionist. No treatment to the oral mucosa will be provided to this group as part of the intervention. Subjects will receive oral care instructions and will be asked to follow SOC oral hygiene instructions at home. | Other: Standard of Care Oral Hygiene<br>* Standard of care oral hygiene- weekly oral care visits with soft-bristled toothbrushing.<br>|
| Experimental: Oral Mucosal Deterging and Dental Prophylaxis (OMDP)<br>Oral Mucosal Deterging & Dental Prophylaxis (OMDP) protocol: Subjects assigned to OMDP will attend weekly intervention visits during which they will have their teeth cleaned and will receive the OMDP intervention as follows: subjects will receive a professional dental prophylaxis including periodontal surface debridement and deterging of the oral mucosal surfaces. Subjects will be asked to follow OMDP oral hygiene instructions at home. | Procedure: Oral mucosal deterging and dental prophylaxis<br>* Subjects will receive a professional dental prophylaxis including periodontal surface debridement [a light-touch, gentle form of instrumentation performed with an ultrasonic instrument to promote plaque removal, to facilitate biofilm disruption and endotoxin flushing, but yet with the preservation of the periodontal cementum] and deterging of the oral mucosal surfaces.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oral mucosal severity | Oral mucositis severity as measured by the World Health Organization's Oral Toxicity Scale (WHO OTS); severity is graded 0 through 4, with 4 being the worst. Grade 0 (none), Grade 1 (oral soreness, erythema), Grade 2 (ulceration, solid diet tolerated), Grade 3 (ulceration, liquid diet only), and Grade 4 (nothing by mouth). | Baseline through 3 months post radiation therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlative measures | Salivary cytokines: Levels of Th1/Th2-type cytokines IL10, IL8, IL12p70, TNF alpha, IL4, IL1b, IL2, IL13, IL5, and IFN gamma will be assessed, in addition to levels of gp340. | Baseline through 3 months post radiation therapy | 
| Oral mucositis assessment | Mucositis will be assessed using the WHO Oral Toxicity Scale (see above) and the NCI Common Terminology Criteria for Adverse Events (grade 1 through 5 with grade 5 being most severe/death) | Baseline through 3 months post radiation therapy | 
| Duration and time to onset of severe OM | OM severity will be measured by a blinded member of the study team using the WHO OTS (previously described) and the duration and time to onset of severe OM measured in days. | Baseline through 3 months post radiation therapy | 
| Salivary hypofunction | Changes in saliva flow rate (mL/minute) will be assessed by a 5 minute stimulated saliva collection. | Baseline through 3 months post radiation therapy | 
| Average mouth and throat soreness | Average mouth and throat soreness (MTS) will be assessed using the validated Oral Mucositis and Daily Questionnaire (Stiff et al.) | Baseline through 3 months post radiation therapy | 
| QOL and Function | Quality of life and function will be assessed using the validated EORTC-QLQ-C30 for head and neck cancers. This questionnaire assesses general quality of life as well as issues specific to head and neck cancer patients (e.g. difficulty swallowing, pain, dry mouth). | Baseline through 3 months post radiation therapy | 
| Progression free survival | Progression free survival | Time from randomization to date of progression or death from any cause, whichever comes first, assessed up to 5 years after completion of RT | 
| Overall survival | Overall survival | Time from randomization to date of death from any cause, assessed assessed up to 5 years after completion of RT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head Cancer, Neck Cancer, Oral Mucositis, Oral Health, Radiation, Chemoradiation