Low-Level Laser Therapy for Prevention of Oral Mucositis

A Phase II Prospective Trial of Low-Level Laser Therapy for Prevention of Oral Mucositis in Patients Receiving Chemotherapy and Radiation for Head and Neck Cancer

The overall purpose of this study is to examine the efficacy of prophylactic low-level laser therapy (LLLT) to reduce the incidence of oral mucositis and adverse events in patients receiving combined modality therapy consisting of chemotherapy and radiation therapy for head and neck cancer.

Study Overview

• Status: Completed
• Conditions: Mucositis
• Intervention / Treatment: Device: Low Level Laser Therapy

Detailed Description

A phase II, single-arm trial to examine the efficacy of prophylactic low-level laser therapy (LLLT) to reduce the incidence of oral mucositis and adverse events in patients receiving combined modality therapy consisting of chemotherapy and radiation therapy for head and neck cancer.

Patients meeting the eligibility criteria will be enrolled to receive prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices.

Patients will receive LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam will be performed to identify any areas of mucositis. If the patient should develop intraoral lesions they will be targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings to be used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.

Patients will be evaluated prior to therapy, weekly during therapy, two weeks after the completion of therapy, and three months after the completion of therapy. During each assessment, the following toxicities will be assessed: pain, mucositis, dysphagia, xerostomia, dysgeusia, dermatitis, trismus, and quality of life.

Previous studies indicate that approximately 40% of patients will experience severe mucositis with radiation and concurrent chemotherapy. The hypothesis in this trial is that the addition of LLLT to this treatment regimen will decrease the rate of severe acute OM to 20%. We plan to enroll 50 patients at our institution.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Shadyside Department of Radiation Oncology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Willing and able to understand and sign informed consent form approved by the HRPO.
• Males or females greater than or equal to 18 years old.
• Biopsy-proven HNC including cancers of the nasopharynx, oropharynx, larynx, hypopharynx, or HNC of unknown primary origin amenable to therapy with radiation and concurrent chemotherapy.
• Patients who are planned to receive definitive or adjuvant radiotherapy with concurrent platinum-based chemotherapy.
• Patients whose clinical treatment plans include a continuous course of external beam radiotherapy by intensity-modulated radiation therapy (IMRT) and/or image-guided radiation therapy (IGRT), given as a cumulative dose of 5000 - 7000 cGy in single daily fractions of 180 - 200 cGy, combined with a concurrent course of weekly or tri-weekly cisplatin or carboplatin chemotherapy.
• Karnofsky performance status score >60.
• Female subjects of child-bearing potential must have a negative pregnancy test prior to enrollment.

Exclusion Criteria:

• Subject has evidence of current mucositis, mucosal ulceration, or unhealed surgical wounds from surgical resection or biopsy.
• Prior radiation to the head and neck.
• Patients with gross tumor involvement of the oral cavity or oral mucosa.
• Subjects planned to receive altered fractionation radiotherapy or multiple fractions per day
• Subject is using a pre-existing feeding tube for nutritional support at the time of study entry.
• Women who are pregnant or breast-feeding.
• Subject plans to receive concurrent chemotherapy, other than the regimens specified in the inclusion criteria.
• Patients who have chronic immunosuppression or are on current immunosuppressive therapies.
• Patients who have a contraindication to radiation therapy.
• Patients enrolled on another investigational trial for oral mucositis prevention.
• Life expectancy of less than 3 months.
• Unable or unwilling to adhere to study-specified procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Low Level Laser Therapy; Patients meeting the eligibility criteria will be enrolled to receive prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices.

Device: Low Level Laser Therapy; Patients will receive LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam will be performed to identify any areas of mucositis. If the patient should develop intraoral lesions they will be targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings to be used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Severe (WHO Grade 3-4) Oral Mucositis	Percentage of participants with severe oral mucositis per the World Health Organization (WHO grade 3-4) (ulcerative lesions of the oral mucosa) in patients treated to a cumulative radiation dose of at least 5000 cGy.	Up to 1 year
Percentage of Participants With Severe (CTCAE v. 4.0 Grade 3-5) Oral Mucositis	The Percentage of participants with severe Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0 grade 3-5) oral mucositis in patients treated to a cumulative radiation dose of at least 5000 cGy.	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Onset of Oral Mucositis	Time to onset of severe oral mucositis following the initiation of radiotherapy. per Common Terminology Criteria for Adverse Events (CTCAE v. 4.0 grade 3-4) oral mucositis following the initiation of radiotherapy.	Up to 1 year
Mean Cumulative Radiation Dose	Mean cumulative radiation dose at time of onset of severe oral mucositis per Common Terminology Criteria for Adverse Events (CTCAE v. 4.0 grade 3-4)	Up to 1 year
Duration of Oral Mucositis	Time from onset of severe oral mucositis per Common Terminology Criteria for Adverse Events (CTCAE v. 4.0 grade 3-4). The duration of SOM is calculated as the time in days between the onset of SOM to the time when the patient is first found to recover from SOM. If the patient do not recover from SOM, the duration is censored at the last observation time.	Up to 1 year
Percentage of Participants With Feeding Tube Replacement	Percentage of participants who require feeding tube placement during treatment.	Up to 1 year
Percentage of Participants With Trismus	Percentage of Participants with trismus (reduced opening of the jaws determined via measurement of interincisal distance). The interincisal distance will be measured in millimeters at the patient's maximum comfortable extent of mouth opening.	Up to 1 year
Quality of Life Via Functional Assessment of Cancer Therapy Head & Neck Cancer (FACT-HN) Questionnaire	This measure is based on a self-administered questionnaire. Responses to each item were on a Likert scale score ranging from 0 to 4. The individual responses were summed to compute subscale scores, and the subscales to compute overall total scores, with higher scores indicating better Quality of Life. FACT-HN includes 2 parts - FACT-G and FACT-HN. The basic FACT-G (general) is comprised of 27 items (0-108). Subscales include Physical Well-Being (0-28), Social/Family Well-Being (0-28), Emotional Well-Being (0-24), and Functional Well-Being, (0-28). Two "Relationship with physician" items (subscale score min/max = 0-8) were added to the FACT-G in this trial, for a total of 29 FACT-G items (total min/max = 0-116). The FACT-HN is comprised of 12 head and neck specific items (0-48). Thus, the overall total possible score range was 0-164. The FACT Head & Neck Trial Outcome Index is a composite score which includes only physical, functional, and FACT-HN, thus a score range from 0-104.	Up to 1 year
Percentage of Participants With Oral Mucositis	The percentage of participants with oral mucositis Common Terminology Criteria for Adverse Events (CTCAE v. 4.0 - all grades) in patients treated to a cumulative radiation dose of at least 5000 cGy.	Up to 1 year
Percentage of Participants With Dysphagia	Percentage of participants with dysphagia per Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0) and via diet assessment.	Up to 1 year
Percentage of Participants With Xerostomia	Percentage of participants with xerostomia (oral dryness) per Common Terminology Criteria for Adverse Events (CTCAE) CTCAE v. 4.0.	Up to 1 year
Percentage of Participants With Dysgeusia	Percentage of participants with dysgeusia (altered taste with/without change in diet (e.g., oral supplements); noxious or unpleasant taste; loss of taste) per Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0).	Up to 1 year
Percentage of Participants With Radiodermatitis	Percentage of participants with radiodermatitis (skin response to ionizing radiation exposure/therapy ranging from erythematous rash to desquamation and necrosis) per Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0).	Up to 1 year
Percentage of Participants With Mouth Pain	Percentage of participants with mouth pain. Mouth pain severity will be assessed using a standard 0-10 scale, with higher scores indicating greater pain.	Up to 1 year
Percentage of Participants With Throat Pain	Percentage of participants with throat pain. Throat pain severity will be assessed using a standard 0-10 scale, with higher scores indicating greater pain.	Up to 1 year
Narcotic Analgesia Use	Percentage of patients using narcotic analgesia during treatment.	Up to 2 years
Breaks in Chemoradiotherapy	Mean number of breaks in chemoradiotherapy with LLLT use.	Up to 2 years

Collaborators and Investigators

• Sponsor: David A. Clump, MD, PhD
• Investigators: Principal Investigator: David A Clump, MD, PhD, UPMC Department of Radiation Oncology

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): November 1, 2020
• Study Completion (Actual): November 1, 2020

Study Registration Dates

• First Submitted: February 10, 2016
• First Submitted That Met QC Criteria: February 11, 2016
• First Posted (Estimate): February 17, 2016

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 12, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Mucositis; Stomatitis
• Other Study ID Numbers: 18-127

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes