Mucositis
Conditions
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 OM to 20%. We plan to enroll 50 patients at our institution.
Interventions
DEVICELow 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.
Sponsors
David A. Clump, MD, PhD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Severe (WHO Grade 3-4) Oral Mucositis | Up to 1 year | 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. |
| Percentage of Participants With Severe (CTCAE v. 4.0 Grade 3-5) Oral Mucositis | Up to 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Oral Mucositis | Up to 1 year | 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. |
| Percentage of Participants With Feeding Tube Replacement | Up to 1 year | Percentage of participants who require feeding tube placement during treatment. |
| Percentage of Participants With Trismus | Up to 1 year | 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. |
| Quality of Life Via Functional Assessment of Cancer Therapy Head & Neck Cancer (FACT-HN) Questionnaire | Up to 1 year | 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. |
| Percentage of Participants With Oral Mucositis | Up to 1 year | 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. |
| Percentage of Participants With Dysphagia | Up to 1 year | Percentage of participants with dysphagia per Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0) and via diet assessment. |
| Mean Cumulative Radiation Dose | Up to 1 year | 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) |
| Percentage of Participants With Dysgeusia | Up to 1 year | 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). |
| Percentage of Participants With Radiodermatitis | Up to 1 year | 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). |
| Percentage of Participants With Mouth Pain | Up to 1 year | Percentage of participants with mouth pain. Mouth pain severity will be assessed using a standard 0-10 scale, with higher scores indicating greater pain. |
| Percentage of Participants With Throat Pain | Up to 1 year | Percentage of participants with throat pain. Throat pain severity will be assessed using a standard 0-10 scale, with higher scores indicating greater pain. |
| Narcotic Analgesia Use | Up to 2 years | Percentage of patients using narcotic analgesia during treatment. |
| Breaks in Chemoradiotherapy | Up to 2 years | Mean number of breaks in chemoradiotherapy with LLLT use. |
| Percentage of Participants With Xerostomia | Up to 1 year | Percentage of participants with xerostomia (oral dryness) per Common Terminology Criteria for Adverse Events (CTCAE) CTCAE v. 4.0. |
| Duration of Oral Mucositis | Up to 1 year | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Level Laser Therapy Patients that received 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.
Low Level Laser Therapy: 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 performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J. | 47 |
| Total | 47 |
Baseline characteristics
| Characteristic | Low Level Laser Therapy |
|---|---|
| Age, Continuous | 60.5 years |
| Alcohol History Alcohol use - No | 18 Participants |
| Alcohol History Alcohol use - Yes | 29 Participants |
| Head Neck Origin Hypopharynx | 1 Participants |
| Head Neck Origin Larynx | 8 Participants |
| Head Neck Origin Nasopharynx | 3 Participants |
| Head Neck Origin Oropharynx | 33 Participants |
| Head Neck Origin Unknown | 2 Participants |
| Positive Karnofsky Performance Status | 47 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 41 Participants |
| Tobacco History Tobacco use - No | 25 Participants |
| Tobacco History Tobacco use - Yes | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 47 |
| other Total, other adverse events | 47 / 47 |
| serious Total, serious adverse events | 18 / 47 |
Outcome results
Primary
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.
Time frame: Up to 1 year
Population: Treated patients experiencing severe oral mucositis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Level Laser Therapy | Percentage of Participants With Severe (CTCAE v. 4.0 Grade 3-5) Oral Mucositis | 23 percentage of participants |
Primary
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.
Time frame: Up to 1 year
Population: Treated patients experiencing severe oral mucositis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Level Laser Therapy | Percentage of Participants With Severe (WHO Grade 3-4) Oral Mucositis | 23 percentage of participants |
Secondary
Breaks in Chemoradiotherapy
Mean number of breaks in chemoradiotherapy with LLLT use.
Time frame: Up to 2 years
Population: Treated patients that experienced breaks in chemoradiotherapy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Level Laser Therapy | Breaks in Chemoradiotherapy | 47.7368 events | Standard Deviation 5.19191 |
Secondary
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.
Time frame: Up to 1 year
Population: Includes only treated patients experiencing severe oral mucositis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Level Laser Therapy | Duration of Oral Mucositis | 24 days |
Secondary
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)
Time frame: Up to 1 year
Population: Includes only treated patients experiencing severe oral mucositis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Level Laser Therapy | Mean Cumulative Radiation Dose | 56 Gy | Standard Deviation 12.8624 |
Secondary
Narcotic Analgesia Use
Percentage of patients using narcotic analgesia during treatment.
Time frame: Up to 2 years
Population: Treated patients that used a narcotic analgesic.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Level Laser Therapy | Narcotic Analgesia Use | 55 percentage of participants |
Secondary
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).
Time frame: Up to 1 year
Population: Treated patients experiencing dysgeusia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Level Laser Therapy | Percentage of Participants With Dysgeusia | 100 percentage of participants |
Secondary
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.
Time frame: Up to 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Level Laser Therapy | Percentage of Participants With Dysphagia | 100 percentage of participants |
Secondary
Percentage of Participants With Feeding Tube Replacement
Percentage of participants who require feeding tube placement during treatment.
Time frame: Up to 1 year
Population: Treated patients who required feeding tube placement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Level Laser Therapy | Percentage of Participants With Feeding Tube Replacement | 36 percentage of participants |
Secondary
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.
Time frame: Up to 1 year
Population: Treated patients experiencing mouth pain.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Level Laser Therapy | Percentage of Participants With Mouth Pain | 94 percentage of participants |
Secondary
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.
Time frame: Up to 1 year
Population: Treated patients experiencing oral mucositis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Level Laser Therapy | Percentage of Participants With Oral Mucositis | 96 percentage of participants |
Secondary
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).
Time frame: Up to 1 year
Population: Treated patients experiencing radiodermatitis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Level Laser Therapy | Percentage of Participants With Radiodermatitis | 100 percentage of participants |
Secondary
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.
Time frame: Up to 1 year
Population: Treated patients experiencing throat pain.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Level Laser Therapy | Percentage of Participants With Throat Pain | 96 percentage of participants |
Secondary
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.
Time frame: Up to 1 year
Population: Treated patients experiencing trismus.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Level Laser Therapy | Percentage of Participants With Trismus | 26 percentage of participants |
Secondary
Percentage of Participants With Xerostomia
Percentage of participants with xerostomia (oral dryness) per Common Terminology Criteria for Adverse Events (CTCAE) CTCAE v. 4.0.
Time frame: Up to 1 year
Population: Treated patients experiencing xerostomia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Level Laser Therapy | Percentage of Participants With Xerostomia | 100 percentage of participants |
Secondary
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.
Time frame: Up to 1 year
Population: Treated patients that completed Fact QoL assessments.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Low Level Laser Therapy | Quality of Life Via Functional Assessment of Cancer Therapy Head & Neck Cancer (FACT-HN) Questionnaire | PHYSICAL WELL BEING (PWB) | 21.5417 score on a scale |
| Low Level Laser Therapy | Quality of Life Via Functional Assessment of Cancer Therapy Head & Neck Cancer (FACT-HN) Questionnaire | SOCIAL/FAMILY WELL BEING (SWB) | 24.3654 score on a scale |
| Low Level Laser Therapy | Quality of Life Via Functional Assessment of Cancer Therapy Head & Neck Cancer (FACT-HN) Questionnaire | EMOTIONAL WELL BEING (EWB) | 20.9167 score on a scale |
| Low Level Laser Therapy | Quality of Life Via Functional Assessment of Cancer Therapy Head & Neck Cancer (FACT-HN) Questionnaire | FUNCTIONAL WELL BEING (FWB) | 18.7708 score on a scale |
| Low Level Laser Therapy | Quality of Life Via Functional Assessment of Cancer Therapy Head & Neck Cancer (FACT-HN) Questionnaire | FACT-G total score (FACTG) | 84.9028 score on a scale |
| Low Level Laser Therapy | Quality of Life Via Functional Assessment of Cancer Therapy Head & Neck Cancer (FACT-HN) Questionnaire | FACT HN | 21.7035 score on a scale |
| Low Level Laser Therapy | Quality of Life Via Functional Assessment of Cancer Therapy Head & Neck Cancer (FACT-HN) Questionnaire | FACT-G with FACT HN total score | 107.403 score on a scale |
| Low Level Laser Therapy | Quality of Life Via Functional Assessment of Cancer Therapy Head & Neck Cancer (FACT-HN) Questionnaire | FACT Head & Neck Trial Outcome Index | 62.4470 score on a scale |
Secondary
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.
Time frame: Up to 1 year
Population: Includes only treated patients experiencing severe oral mucositis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Level Laser Therapy | Time to Onset of Oral Mucositis | NA days |