Celecoxib Through Surgery and Radiation Therapy for the Treatment of Advanced Head and Neck Cancer

This phase II trial studies how well celecoxib works through surgery and radiation therapy in treating patients with head and neck cancer that has spread to other places in the body (advanced). Celecoxib is Food and Drug Administration approved to treat arthritis, acute pain, and painful menstrual periods. Adding celecoxib to standard of care treatment may help to decrease the amount of time between surgery and radiation therapy.

PRIMARY OBJECTIVE:

I. To assess the number of days from surgery to initiation of radiation with the addition of celecoxib compared to placebo.

SECONDARY OBJECTIVES:

I. To assess overall pain control and management for patients on celecoxib compared to placebo.

* Subjective pain scores on the visual analog scale of pain intensity averaged over a week at rest, with a swallow, and with a cough.
* Patient satisfaction with pain control questionnaire.
* Narcotic consumption in daily total morphine equivalents averaged over a week. II. To assess functional outcomes for patients on celecoxib compared to placebo.

III. To assess the effect of celecoxib therapy on Quality of Life (QoL) compared to placebo.

IV. To assess the average number of treatment days missed during adjuvant radiation for patients on celecoxib compared to placebo.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive celecoxib orally (PO) or via feeding tube twice daily (BID) starting 5 days prior to surgery and continues until the completion of radiation therapy (up to 6 months in total) in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO or via feeding tube BID starting 5 days prior to surgery and continues until the completion of radiation therapy (up to 6 months in total) in the absence of disease progression or unacceptable toxicity.

Eligibility Criteria:
Inclusion Criteria:

* Male or female subject aged ≥ 18 years.
* Advanced-stage (overall stage III and IV) head and neck cancers (sinonasal oral cavity, oropharynx, larynx, and hypopharynx) undergoing surgical resection and then adjuvant radiation. Primary and recurrence cases are acceptable
* Karnofsky performance status of \>= 70
* Hemoglobin \>= 10 g/dL
* Total bilirubin =\< 2 mg/dL
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (ULN)
* Albumin \> 3.5 g/dL
* Estimated glomerular filtration rate (eGFR) \>= 30 mL/min/1.73 m\^2 or creatinine clearance \>= 30 mL/min by Cockcroft-Gault
* Serum potassium within normal limits
* Negative serum or urine pregnancy test at screening for women of childbearing potential
* Highly effective contraception for female subjects throughout the study and for at least 5 days after the last dose of study therapy if the risk of conception exists
* Recovery to baseline or =\< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
* Willing to maintain a diary of all opioids used during the trial for the treatment of pain
* Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
* Subject has verbally confirmed they are willing to complete adjuvant radiation therapy if recommended after surgery per protocol.
* Adjuvant radiation has been recommended by the institutional treatment planning conference with the best available data, but will be confirmed based on final surgical pathology.

Exclusion Criteria:

* Known distant metastatic disease or the tumor is deemed not surgically resectable
* Established in a pain management clinic or has taken opioids regularly \>= 6 months
* Known or suspected to be poor CYP2C9 metabolizers based on previous history/experience with other CYP2C9 substrates (such as warfarin, phenytoin)
* Known hypersensitivity to celecoxib, aspirin, other non-steroidal anti-inflammatory drug (NSAID)s, or sulfonamides
* Uncontrolled hypertension defined as blood pressure (BP) \> 150 mmHg systolic or \> 90 mmHg diastolic on three consecutive reads, taken in one sitting despite optimal antihypertensive treatment
* Patients with a known history of the following:

  * Cerebrovascular accident (CVA), stroke, or cardiovascular thrombotic events (e.g. acute myocardial infarction).
  * Chronic heart failure.
  * Gastrointestinal bleeding, ulceration, peptic ulcer disease, or perforation of the stomach or intestines.
  * Aspirin-sensitive asthma.
  * Chronic kidney disease, stage 4 or 5
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* The subject has uncontrolled, significant intercurrent or recent illness requiring systemic therapy, would preclude safe study participation, or is deemed clinically significant by the investigator
* Known human immunodeficiency virus (HIV) infection with a detectable viral load within 6 months of the anticipated start of treatment.

  * Note: Patients on effective anti-retroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial
* Known chronic hepatitis B virus (HBV) or hepatitis C virus infection with a detectable viral load.

  * Note: Patients with an undetectable HBV viral load on appropriate suppressive therapy are eligible. Patients with an undetectable hepatitis C virus (HCV) viral load on appropriate treatment are eligible
* Subjects taking prohibited medications . A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur prior to the start of treatment