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

Study Overview
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Brief Summary
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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
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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. 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.

Official Title
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RESILIENCE: Effect of Comprehensive Celecoxib Through Treatment for Advanced-Stage Head and Neck Cancer: A Randomized, Double-Blinded, Placebo-Controlled Trial

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

Intervention / Treatment
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* Drug: Celecoxib
* Other: Placebo
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 >= 80 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 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

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Celecoxib Arm<br>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. | Drug: Celecoxib<br>* Given PO or via feeding tube<br>* Other names: YM 177;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Placebo Comparator: Placebo Arm<br>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. | Other: Placebo<br>* Given PO or via feeding tube<br>* Other names: sham therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of days from surgery to the initiation of radiation and adjuvant therapy | The day of surgery will be considered day 0 and the number of days will be counted until the first dose of adjuvant radiation. A Gaussian mixed effects regression model will be used to compare the average number of days from surgery to the initiation of radiation and adjuvant therapy between treatment and control groups. The model will contain fixed effects for treatment arm and provider and a nested random effect for patient within provider. The mean difference between treatment groups, two-sided p-value and 95% confidence interval will be calculated from the model. | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of overall pain control and management for patients on celecoxib compared to placebo. | 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. Pain intensity scale is a range from 0-10. 0= No Pain, 5= Moderate pain, 10= Unbearable paining | Up to 3 years | 
| Assessment of functional outcomes for patients on celecoxib compared to placebo | Assessment of current activity level and swallowing capabilities, including food and liquid variety and assessment of G tube utilization. | Up to 3 years | 
| To assess the effect of celecoxib therapy on Quality of Life (QoL) compared to placebo. | Completion of quality of life questionnaire EORTC QLQ-H&N43 as per the protocol described schedule. | Up to 3 years | 
| Assessment of the average number of treatment days missed during adjuvant radiation for patients on celecoxib compared to placebo. | Assess the number of treatment days missed or delayed during adjuvant radiation. | up to 3 years | 
| Assessment of overall pain control and management for patients on celecoxib compared to placebo. | Narcotic consumption will be assessed in daily total morphine equivalents averaged over a week | up to 3 years | 
| Assessment of overall pain control and management for patients on celecoxib compared to placebo. | Patient satisfaction will be assessed with pain control questionnaire. | up to 3 years | 
| To assess the effect of celecoxib therapy on Quality of Life (QoL) compared to placebo. | Completion of quality of life questionnaire MDASI-HN as per the protocol described schedule. | up to 3 years |