• Oral Mucositis (OM) Grade and Incidence, [ Time Frame: 6-8 weeks, evaluated once per week ]
  Radiation therapy oncology group scale (RTOG) 0 (Normal)- 4 (necrosis/hemorrhage), 5= death
• Oral Mucositis (OM) Grade and Incidence, [ Time Frame: 6-8 weeks, evaluated once per week ]
  World Health Organization scale (WHO) 0 (Normal)- 4 (oral alimentation not possible), 5= death
• Analgesic Usage [ Time Frame: 6-8 weeks, evaluated daily ]
  World Health Organization (WHO) analgesic ladder Steps 1-3: 1= non opioid, 2= weak opioid, 3= strong opioid

• Oral Mucositis (OM) Grade and Incidence, [ Time Frame: 6-8 weeks, evaluated once per week ]
  Radiation therapy oncology group scale (RTOG) 0 (Normal)- 4 (necrosis/hemorrhage), 5= death
• Oral Mucositis (OM) Grade and Incidence, [ Time Frame: 6-8 weeks, evaluated once per week ]
  World Health Organization scale (WHO) 0 (Normal)- 4 (oral alimentation not possible), 5= death
• Analgesic Usage, Pain [ Time Frame: 6-8 weeks, evaluated daily ]
  World Health Organization (WHO) analgesic ladder Steps 1-3: 1= non opioid, 2= weak opioid, 3= strong opioid

Study Design: A prospective, multi-center, randomized, double-blind, placebo controlled, adaptive sample size, two-treatment parallel, pivotal clinical study.

Protocol-eligible subjects will be randomized in a 2:1 allocation to receive either the active MuReva Phototherapy System or sham control. Both the subjects and clinician evaluating the patients will be blinded to the treatment assignments. The sham device will be placed in the patient's mouth and operated in the same manner as the active device, but not deliver any therapy.

Subjects will begin device treatment sessions on the first day of chemoradiotherapy (CRT) treatment immediately prior to radiation treatment (RT) and will continue to receive once daily treatments prior to RT with their assigned device for 5 days per week for the duration of their CRT treatment (approximately 6 to 8 weeks, for a total of 30 to 40 device sessions depending on the standard of care regimen for the type of cancer). Each device treatment session will last 5 minutes. Light therapy parameters for the MuReva Phototherapy System will be as follows for all subjects receiving active light therapy: mouthpiece 660nm, 2-8 J/cm2, irradiance < 75mW/cm2. Subjects who stay on CRT treatment past 6 weeks will continue to receive treatment with their assigned device up through 8 total weeks of treatment (for a maximum total of 40 device sessions). In addition, all subjects, regardless of randomization, will be kept on standard oral care, oral hygiene and oral pain protocols.

All subjects will visit the study site once during the Screening period (Days -28 to 1) an anticipated 30 to 40 times during the treatment period (i.e., 5 days during each of the 6-8 CRT treatment weeks) and for one 2-week post RT follow-up visit. Weekly, subjects will be evaluated for QOL, pain, OM and for device safety. At the conclusion of the final CRT session and evaluation, each subject will complete a user validation survey. There will be one 2-week post RT follow-up visit.

• Oral Mucositis (Ulcerative)
• Oral Mucositis (Ulcerative) Due to Radiation
• Oral Mucositis (Ulcerative) Due to Antineoplastic Therapy
• Head and Neck Cancer

• Device: Photobiomodulation
  Provide photobiomodulation therapy to subjects prior to each radiation therapy session.
  Other Name: low-level laser therapy
• Other: Routine Oral Care and Analgesia
  Standard oral care, oral hygiene and oral pain protocols
  Other Name: Pain medication, oral rinses

• Active Comparator: Active Device Treatment Cohort
  The MuReva Phototherapy System consists of Light Control Unit and a Mouthpiece Cable Assembly. Subjects will begin device treatment photobiomodulation sessions on the first day of radiotherapy (RT) treatment. They will receive once-daily investigative device photobiomodulation treatments prior to radiation therapy (RT) with their assigned Mouthpiece for 5 days per week for the duration of their CRT treatment. Each device treatment session will last up to 5 minutes, not including up to 5 additional minutes for treatment breaks. All subjects will visit the study site once during the Screening period (Days -28 to 1) and an anticipated 30 to 40 times during the treatment period. Each patient will be assigned their own Mouthpiece Cable Assembly.
  Interventions:

  • Device: Photobiomodulation
  • Other: Routine Oral Care and Analgesia
• Sham Comparator: Sham Device Treatment Cohort
  The MuReva Phototherapy System (or sham control) is a Light Control Unit and a Mouthpiece Cable Assembly. The sham control Mouthpiece Cable Assembly will appear identical to the active Mouthpiece Cable Assembly, and will be used in the same manner as the active cohort. However, the sham control device will be configured where the mouthpiece will not emit any light at any time during the study. The same Light Control Unit will be used with sham and active Mouthpiece Cable Assemblies. Each patient will be assigned their own Mouthpiece Cable Assembly.
  Intervention: Other: Routine Oral Care and Analgesia

Inclusion Criteria:

1. Subject has been diagnosed with pathologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, tonsil or base of tongue.
2. Within 28 days of Screening, subject is scheduled to receive a continuous course of Intensity-Modulated Radiation Therapy (IMRT) over an estimated 6 to 8 weeks (treatment week is defined as 5 fractions per week). The initial target volume encompassing the gross and subclinical disease sites will receive 5 fractions per week with a minimum cumulative dose of 50 Gray (Gy) for low to intermediate risk (sites of suspected subclinical spread) and maximum cumulative dose of 70 Gy for gross tumor volume/High risk (Primary tumor and involved lymph nodes).
3. The subject's planned radiation treatment fields include at least one oral site (buccal mucosa, floor of mouth, ventral/lateral tongue, soft palate, oropharynx);
4. The subject's treatment plan includes chemotherapy with cisplatin administered in either a standard weekly (30-40 mg/m2) or approximately every 21 days (80-100mg/m2) regimen AND/OR paclitaxel administered in a standard weekly (30-45mg/m2) regimen in combination with carboplatin administered in standard weekly (1.0-2.0 AUC) regimen;
5. Subject is at least 22 years of age;
6. Subject has no dental or oral health conditions that would preclude daily use of a mouthpiece;
7. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2;
8. Subject is able to read and understand the Informed Consent Form (ICF) and has voluntarily provided written informed consent;
9. Subject demonstrates capability in sustaining mouthpiece in oral cavity for recommended time during Screening procedure
10. Subject demonstrates willingness to adhere to the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

1. Subject is currently receiving, or has previously received chemotherapy or chemoradiotherapy within the past 2 years;
2. Subject has previously been diagnosed with another type/site of cancer that has not been controlled or has been active in the past 2 years.
3. Subject is pregnant or nursing;
4. Subject is receiving medications indicated for the treatment and/or prevention of mucositis (e.g., palifermin);
5. Subject has had prior radiation to the head and neck;
6. Subject has a diagnosis that is prone to affect wound healing, e.g., uncontrolled diabetes;
7. Subject has trismus with an interincisal distance of 30mm or less
8. Subject has an active infection in the oropharynx or oral cavity;
9. Subject has a salivary disturbance, e.g., Sjögren's syndrome;
10. Subject has any grade of oral mucositis (per WHO Oral Toxicity Scale);
11. Subject is receiving, or has received in the last 30 days, an investigational treatment, therapy, or medical device outside of this clinical study protocol;
12. Subject has a visual analog pain scale (VAS) score of 5 or greater localized to the oral cavity but is NOT tumor related.
13. Subject is unable to participate in the study because of a concurrent disease state that, in the opinion of the Principal Investigator, would affect the study endpoints, e.g., dental disease or COVID19 (SARS-CoV-2 infection active or recovered).
14. Subject is currently using, and/or has used in the last 30 days, any tobacco or nicotine products, with the exception of nicotine patches.
15. Subject is currently taking, or has taken in the last month, any marijuana (Cannabis sativa or Cannabis indica), or illicit drugs.
16. Subject has 8 or more crowns OR subject is not considered eligible at the discretion of the oral maxillofacial dentist/surgeon.