Low-Level Laser Therapy for Prevention of Oral Mucositis

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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

Conditions
-----------------
Mucositis

Intervention / Treatment
-----------------
* Device: Low Level Laser Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Low Level Laser Therapy<br>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<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |