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 oral mucositis (OM) to 20%. We plan to enroll 25 patients at our institution in 12 months after the trial opens.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute

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 institutional review board (IRB)
• Males or females greater than or equal to 18 years old
• Biopsy-proven head and neck cancer (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 centigray (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 patients of child-bearing potential must have a negative pregnancy test prior to enrollment

Exclusion Criteria:

• Patient 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
• Patient planned to receive altered fractionation radiotherapy or multiple fractions per day
• Patient is using a pre-existing feeding tube for nutritional support at the time of study entry
• Women who are pregnant or breast-feeding
• Patient 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: 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	Time Frame
Number of Participants With Severe (Common Terminology Criteria for Adverse Events Version 4.0 [CTCAE v. 4.0] Grade 3-5 Oral Mucositis in Patients Treated to a Cumulative Radiation Dose of at Least 5000 cGy	From beginning of therapy up to 3 months after completion of therapy
Number of Participants With Severe World Health Organization [WHO] (Grade 3-4) Oral Mucositis in Patients Treated to a Cumulative Radiation Dose of at Least 5000 cGy	From beginning of therapy up to 3 months after completion of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in OM-related QOL Assessed Using FACT Questionnaire	The QOL assessment taken at the beginning of therapy is subtracted from the QOL assessment taken at the completion of therapy. The QOL scale is the FACT Questionnaire. Measure on a scale of 0 to 4. 0 = not at all and 4= very much.	From beginning of therapy up to completion of therapy
Duration of Oral Mucositis	Survival analysis was used to estimate the duration of oral mucositis. Patients were censored if oral mucositis not resolved by the end of the study.	From beginning of therapy up to 3 months after completion of therapy
Number of Participants With Any Grade Oral Mucositis in Patients Treated to a Cumulative Radiation Dose of at Least 5000 cGy	Grade of oral mucositis assessed using the NCI CTCAE version 4.0	From beginning of therapy up to 3 months after completion of therapy
Number of Participants With Dysgeusia Assessed by CTCAE v. 4.0	Variable is reported on the 1-5 CTCAE scale: - Mild; - Moderate; - Severe; - Life-threatening; - Death The maximum recorded severity is reported.	From beginning of therapy up to 3 months after completion of therapy
Number of Participants With Dysphagia Assessed by CTCAE v. 4.0 and Diet Assessment	Variable is reported on the 1-5 CTCAE scale: - Mild; - Moderate; - Severe; - Life-threatening; - Death The maximum recorded severity is reported.	From beginning of therapy up to 3 months after completion of therapy
Number of Participants With Pain as Assessed by the Visual Analogue Scale (VAS)	Variable is reported on the 1-10 scale Higher values represent a worse outcome The maximum recorded severity is reported	From beginning of therapy up to 3 months after completion of therapy
Number of Participants With Radiodermatitis Assessed by CTCAE v. 4.0	Variable is reported on the 1-5 CTCAE scale: - Mild; - Moderate; - Severe; - Life-threatening; - Death The maximum recorded severity is reported.	From beginning of therapy up to 3 months after completion of therapy
Number of Participants With Trismus Assessed by Measurement of Interincisal Distance	Trismus is defined as a measurement of interincisal distance less than or equal to 30mm.	From beginning of therapy up to 3 months after completion of therapy
Number of Participants With Xerostomia Assessed by CTCAE v. 4.0	Variable is reported on the 1-5 CTCAE scale: - Mild; - Moderate; - Severe; - Life-threatening; - Death The maximum recorded severity is reported.	Up to 3 months after completion of therapy
Mean Cumulative Radiation Dose at Time of Onset of Severe (CTCAE v. 4.0 Grade 3-4) Oral Mucositis	The reported dose is at the first incidence of severe oral mucositis.	From beginning of therapy up to 3 months after completion of therapy
Time to Onset of Severe (CTCAE v. 4.0 Grade 3-4) Oral Mucositis Following the Initiation of Radiotherapy	Survival analysis is used to analyze this endpoint	From beginning of therapy up to 3 months after completion of therapy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of Narcotic Analgesia Use During Treatment		From beginning of therapy up to 3 months after completion of therapy
Number of Participants With Breaks in Treatment	Breaks in treatment defined as one of the following: Missing at least 1 chemotherapy treatment; dose reduction in planned cisplatin administration; OR 3 consecutive days of no radiation therapy secondary to mucositis	Date of completion of chemoradiation therapy
Percent Change in Body Weight During the Course of Treatment	The percent change in body weight was computed by subtracting the baseline weight from the weight after completion of treatment and dividing that quantity by the baseline weight. The confidence interval is estimated using the t distribution.	From date of enrollment until the date of completion of chemoradiation therapy, assessed up to 3 months after completion of therapy
Number of Participants Who Require Feeding Tube Placement During Treatment (Excluding Patients Who Received a Prophylactic Feeding Tube Prior to the Initiation of Therapy)		At the date of completion of chemoradiation therapy
Number of Participants With Severe (CTCAE v. 4.0 Grade 3-4) Oral Mucositis by 5000 and 7000 cGy		From beginning of therapy up to 3 months after completion of therapy
Number of Participants With Severe (CTCAE v. 4.0 Grade 3-4) Oral Mucositis by Schedule of Chemotherapy Given Weekly Versus Every 3 Weeks		From beginning of therapy up to 3 months after completion of therapy
Time to Reach Planned Dose of Radiation Therapy	Kaplan-Meier methods are used to estimate time until reaching planned dose.	From the beginning of therapy up to completion of therapy (9 weeks maximum)

Collaborators and Investigators

• Sponsor: Barbara Ann Karmanos Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Harold Kim, Barbara Ann Karmanos Cancer Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): August 2, 2017
• Study Completion (Actual): September 13, 2021

Study Registration Dates

• First Submitted: March 21, 2016
• First Submitted That Met QC Criteria: March 24, 2016
• First Posted (Estimate): March 30, 2016

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

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: 2015-170 (Other Identifier: Wayne State University/Karmanos Cancer Institute); P30CA022453 (U.S. NIH Grant/Contract); NCI-2016-00406 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The same protocol will be opened separately at the University of Pittsburgh Medical Center, where an additional 25 patients will be enrolled. A Data Use Agreement will allow combination of the data for a total of 50 patients to be analyzed.