This 2-arm phase II study proposes to determine the efficacy of ketamine oral rinse in pain relief from mucositis in head and neck cancer patients undergoing radiation treatment.

Patients with histologically proven head and neck cancer undergoing radiation or concurrent chemoradiation as part of their treatment plan, will either receive ketamine oral rinse or unmedicated oral rinse to use 4 times a day if they develop oral mucositis during their radiation.

Patients will be monitored during treatment and up to 30 days after and will utilize a pain diary to document daily.

Inclusion Criteria:

1. Written informed consent signed and dated by the patient prior to the performance of the study-specific procedure.
2. At least 18 years-of-age at the time of signature of the informed consent form (ICF).
3. Patients with histologically proven HNSCC undergoing radiation of concurrent chemoradiation as part of their treatment plan.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2.
5. The patients has received at least one radiation treatment for (HNSCC) the current disease.
6. CTCAE v. 5.0 grade 2 or greater oral cavity or pharyngeal mucositis documented to have developed after initiation of radiotherapy.
7. Males or female patients. Male patients with female partners of childbearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 30 days following last dose. Male patients must also refrain from donating sperm during participation in the study.

Exclusion Criteria:

1. Inability to sign an informed consent form.
2. Any other malignancy diagnosed or treated within 10 years prior to enrollment.
3. Any documented hypersensitivity to ketamine.
4. Contraindication for ketamine use, including allergy.
5. Patients with schizophrenia, acute psychosis, or any psychiatric disorder that could be dangerous if exacerbated.
6. Women who are pregnant, nursing, or who plan to become pregnant while in the study and for at least <<6>> months after the last administration of study treatment.
7. Men who plan to father a child while in the study and for at least 6 months after the last administration of study treatment.
8. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus. Screening for chronic conditions is not required.
9. Patients with a prior or concurrent malignancy whole natural history or treatment does not have potential to interfere with the safety or efficacy assessment of the investigational regimen should be included.
10. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.

The principal investigator and pharmacist will be the only ones who are aware of whom gets which arm of the study.