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

Phase 2

Terminated

Conditions: Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Oral Cavity Carcinoma
Recurrent Hypopharyngeal Carcinoma
Recurrent Nasal Cavity and Paranasal Sinus Carcinoma
Stage III Laryngeal Cancer AJCC v8
Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Stage IVA Laryngeal Cancer AJCC v8
Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Recurrent Oral Cavity Carcinoma
Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8

Interventions: Drug: Celecoxib
Other: Placebo
Other: Quality-of-Life Assessment
Other: Questionnaire Administration

Registration Number: NCT04162873

Lead Sponsor: University of Utah

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 13

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Celecoxib Arm	Quality-of-Life Assessment	Patients receive celecoxib PO or via feeding tube BID starting 1 to 7 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.
Celecoxib Arm	Questionnaire Administration	Patients receive celecoxib PO or via feeding tube BID starting 1 to 7 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.
Celecoxib Arm	Celecoxib	Patients receive celecoxib PO or via feeding tube BID starting 1 to 7 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.
Placebo Arm	Placebo	Patients receive placebo PO or via feeding tube BID starting 1 to 7 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.
Placebo Arm	Quality-of-Life Assessment	Patients receive placebo PO or via feeding tube BID starting 1 to 7 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.
Placebo Arm	Questionnaire Administration	Patients receive placebo PO or via feeding tube BID starting 1 to 7 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.

Primary Outcome Measures

Name	Time	Method
The Number of Days From Surgery to the Initiation of Radiation and Adjuvant Therapy	up to 3 months	The day of surgery will be considered day 0 and the number of days will be counted until the first dose of adjuvant radiation. This outcome measure will report the mean number of days from surgery to the initiation of radiation and adjuvant therapy for the Celecoxib and Placebo Arms.

Secondary Outcome Measures

Name	Time	Method
Assessment of Overall Pain Control and Management for Patients on Celecoxib Compared to Placebo - Visual Analog Scale.	Up to 29 days from the start of study treatment	Assessment of subjective pain scores on the visual analog scale of pain intensity averaged over a week at rest, with a swallow, and with a cough. The subjects rated their pain from 0-10 on the pain intensity scale. Scores are reported as means of the pain score with standard deviation. This outcome is reported scores collected at the post-surgery visit; 9 to 29 days after the start of study treatment.
Assessment of Overall Pain Control and Management for Patients on Celecoxib Compared to Placebo - Pain Control Questionnaire.	post-surgery (up to 29 days from surgery) and end of treatment (up to 5 months from surgery)	Patient satisfaction was assessed with a pain control questionnaire. The participants were asked questions about their pain satisfaction over the last seven days. The pain control questionnaire was scored from 0-100, with smaller values indicating poor pain control satisfaction and larger values indicating excellent pain control satisfaction. This outcome was assessed at post-surgery and end of treatment for up to 5 months
Assessment of Overall Pain Control and Management for Patients on Celecoxib Compared to Placebo.	Post-Surgery (1-7 days) up to 7 days, Post-Surgery (1-14 days) up to 14 days, Post-Surgery (1-26 days) up to 26 days, Post-Surgery (1-35 days) up to 35 days, and End of Treatment up to 146 days.	Narcotic consumption was assessed in daily total morphine equivalents averaged over a week. This outcome was assessed at 7 days after surgery and 35 days after surgery. Morphine equivalent dose (MED) is the amount of opioid prescription drugs a patient is taking per day. MED is the sum of the total morphine milligram equivalents (MMEs), a common unit for assessing milligrams of morphine, dose per day. The Post-Surgery (1-7 days) time point is MED from 1 to 7 days after surgery. The Post-Surgery (1-14 days) time point is MED from 1 to 14 days after surgery. The Post-Surgery (1-26 days) time point is MED from 1 to 26 days after surgery. The Post-Surgery (1-35 days) time point is MED from 1 to 35 days after surgery. The End of Treatment time point is MED from 1 to 146 days after surgery.
Assessment of Functional Outcomes for Patients on Celecoxib Compared to Placebo	Post-Operation (up to 29 days after surgery), Mid Radiation (up to 112 days after surgery), and End of Treatment (up to 146 days after surgery)	Assessment of swallowing capabilities was assessed by determining gastrostomy tube (G-tube) utilization at the following time points: pre-operation, day 14 of adjuvant therapy, and end of treatment (or last assessment). A G-tube is a tube inserted surgically through the abdomen and into the stomach to deliver liquids, medications, and nutrients directly into the stomach. The responses in this outcome measure are Yes (G-tube is being utilized), No (G-tube is not being utilized), and Not Assessed (G-tube utilized was not assessed). This assessment was measured at Post-Operation (up to 29 days after surgery), Mid Radiation (up to 112 days after surgery), and End of Treatment (up to 146 days after surgery).
To Assess the Effect of Celecoxib Therapy on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-HN43) Compared to Placebo.	Up to 29 days after surgery (up to 32 days after initiation of study treatment)	The EORTC QLQ-HN43 is a 43-question assessment for determining the health-related quality of life of head and neck cancer patients participating in clinical trials. Patients indicate which symptoms/problems they have experienced during the past week, from "1 Not at All" to "4 Very Much". The assessment was scored according to the "EORTC QLQ-C30 Scoring Manual", reporting data as 19 subscales with scores from 0-100. A high scale score represents a higher response level. A high functional scale score (FS) represent a high/healthy level of function and includes body image, social contact, \& sexuality A high symptom scale score (SS) represent a high level of symptomatology/problems and includes anxiety, cough, head and neck pain, swallowing, neurologic problems, senses, speech, social eating, weight loss, problems w/ skin, shoulder, wound healing, dry mouth, opening mouth, neck swelling, \& teeth. This outcome will report the mean score of each subscale.
To Assess the Effect of Celecoxib Therapy on the MDASI-HN Questionnaire Compared to Placebo.	Up to 29 days after surgery (up to 32 days after initiation of study treatment)	This outcome will report the quality of life questionnaire, the M. D. Anderson symptom inventory head neck (MDASI-HN) at the Post-Operation Visit. This was assessed up to 29 days after surgery (up to 32 days after initiation of study treatment). MDASI-HN is a 28-question, 2-part questionnaire for patients with head and neck cancer that assesses the severity of symptoms and impact on daily life. In Part I, subjects indicated how severe their symptoms were from "0 Not present" to "10 As Bad as You can Imagine". In Part II, subjects indicated how symptoms have interfered with their live from "0 Did not Interfere" to "10 Interfered Completely". This assessment was scored according to the The M. D. Anderson Symptom Inventory User Guide.
Assessment of the Average Number of Treatment Days Missed During Adjuvant Radiation for Patients on Celecoxib Compared to Placebo.	up to 140 days	This outcome will report the number of participants who missed treatment days during adjuvant radiation, who did not miss any treatment days during adjuvant radiation, and the number of participants who did not start adjuvant radiation therapy.