Cox-2 Inhibition in Radiation-induced Oral Mucositis

Cyclooxygenase-2 Inhibition in Radiation-Induced Oral Mucositis

Oral mucositis refers to ulcerative lesions of the oral mucosa that occur due to radiation therapy given for treatment of head and neck cancer. These lesions are painful, compromise nutrition and quality of life and may necessitate interruptions in radiation therapy, thus adversely affecting cancer therapy outcomes. This study examined the use of an anti-inflammatory medicine to reduce pain and severity of oral mucositis.

Study Overview

• Status: Completed
• Conditions: Oral Mucositis
• Intervention / Treatment: Drug: celecoxib; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Farmington, Connecticut, United States, 06030-1605
      • University of Connecticut Health Center
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Patients who will be receiving at least 5000 centigray (cGy) radiation therapy to at least 2 of 14 pre-defined areas in the oral cavity.
• Women of childbearing potential must agree to use a medically accepted form of contraception during the course of the study. Women of childbearing potential must have a documented negative pregnancy test within fourteen days of enrollment in the study.
• Patient's willing and able to provide written informed consent for the study.

Key Exclusion Criteria:

• Patients with known hypersensitivity to celecoxib or other COX-2 inhibitors.
• Patients who have experienced asthma, urticaria, or allergic-type reactions after taking salicylates (e.g. aspirin) or Non-steroidal anti-inflammatory drugs (NSAIDs).
• Patients who have demonstrated allergic-type reactions to sulfonamides.
• Patients with a history of gastric, esophageal, pyloric channel or duodenal ulcer disease or gastrointestinal bleeding.
• Patients with a history of inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis) or pancreatic disease.
• Patients with severe hepatic impairment.
• Patients with advanced renal disease.
• Patients with a significant bleeding disorder.
• Patients under the age of 18 or over the age of 75.
• Women who are pregnant or nursing.
• Patients with a history of thromboembolic events including myocardial infarction, pulmonary embolism, deep venous thrombosis, transient ischemic attack and ischemic cerebrovascular accident (stroke).
• Patients who have had coronary angioplasty, coronary artery bypass surgery or another cardiac revascularization procedure.
• Patients with a history of a cardiac arrhythmia requiring anti-arrhythmic therapy, angina pectoris or congestive heart failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I- Celecoxib	Drug: celecoxib; Subject was asked to take celecoxib each day that radiation therapy was given.; Other Names: Celebrex
Placebo Comparator: II	Drug: placebo; Subject was asked to take placebo each day that radiation therapy was given.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Oral Mucosal Injury Score at Cumulative Radiation Dose of 5000 cGy	Oral Mucositis Assessment Scale (OMAS) was used to assess oral mucosal injury during the period of radiation therapy. This validated scale scores ulceration and erythema independently at nine specified sites in the oral cavity. Ulceration is scored from 0-3 based on size of lesion and erythema is scored from 0-2 based on severity of erythema. The sum of scores is then divided by 9. The mean OMAS score at a cumulative radiation dose of 5000 cGy (approximately 5 weeks of treatment) was compared between groups.	5 weeks from start of radiation therapy (5000 cGy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Pain Severity at 5000 cGy Radiation	Mean worst pain at 5000 cGy on 0-10 scale, 0 = no pain, 10 = worst pain imaginable	5 weeks from start of radiation therapy (cumulative dose of 5000 cGy)

Collaborators and Investigators

• Sponsor: UConn Health
• Collaborators: Pfizer; National Institute of Dental and Craniofacial Research (NIDCR)
• Investigators: Principal Investigator: Rajesh V Lalla, DDS, Ph.D, CCRP, UConn Health

Publications and helpful links

General Publications

• Lalla RV, Choquette LE, Curley KF, Dowsett RJ, Feinn RS, Hegde UP, Pilbeam CC, Salner AL, Sonis ST, Peterson DE. Randomized double-blind placebo-controlled trial of celecoxib for oral mucositis in patients receiving radiation therapy for head and neck cancer. Oral Oncol. 2014 Nov;50(11):1098-103. doi: 10.1016/j.oraloncology.2014.08.001. Epub 2014 Aug 21.

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: June 12, 2008
• First Submitted That Met QC Criteria: June 16, 2008
• First Posted (Estimate): June 17, 2008

Study Record Updates

• Last Update Posted (Estimate): June 5, 2014
• Last Update Submitted That Met QC Criteria: May 7, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; Mucositis; Head and Neck Neoplasms; Stomatitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Mucositis; Stomatitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: IRB 03 -157- 2; GCRC 487 (Other Identifier: UCHC Clinical Research Center); COXAON-0509-150 (Other Identifier: Pfizer, Inc.); K23DE016946-05 (U.S. NIH Grant/Contract)