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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low Level Laser Therapy | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low Level Laser Therapy | Device | 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. |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David A Clump, MD, PhD | UPMC Department of Radiation Oncology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UPMC Shadyside Department of Radiation Oncology | Pittsburgh | Pennsylvania | 15232 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Treated patients experiencing severe oral mucositis. | Posted | Number | 90% Confidence Interval | percentage of participants | Up to 1 year |
|
Adverse Events monitored up to 24 months, All-Cause Mortality monitored up to 36 months
Adverse Events: Grade 1 and Grade 2 events per CTCAE v4.0 Serious Adverse Events: Grade 3 and Grade 4 events per CTCAE v4.0
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Oral Mucositis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Oral Mucositis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Barbara Stadterman, MPH, Regulatory Specialist Supervisor | UPMC Hillman Cancer Center | 412-647-5554 | stadtermanbm@upmc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 3, 2015 | Nov 21, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D052016 | Mucositis |
| ID | Term |
|---|---|
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D009059 | Mouth Diseases |
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| ID | Term |
|---|---|
| D028022 | Low-Level Light Therapy |
| ID | Term |
|---|---|
| D053685 | Laser Therapy |
| D013812 | Therapeutics |
| D010789 | Phototherapy |
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|
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 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Head Neck Origin | Count of Participants | Participants |
|
| Tobacco History | Count of Participants | Participants |
|
| Alcohol History | Count of Participants | Participants |
|
| Positive Karnofsky Performance Status | Patients with a performance status score >60. The Karnofsky Performance Scale is an assessment tool of functional impairment to assess the prognosis in individual patients. The score is from 0-100%, with lower Karnofsky scores indicating the lower likelihood of survival. | Number | participants |
|
|
|
| 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. | Treated patients experiencing severe oral mucositis. | Posted | Number | 90% Confidence Interval | percentage of participants | Up to 1 year |
|
|
|
| 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. | Includes only treated patients experiencing severe oral mucositis | Posted | Median | 95% Confidence Interval | days | Up to 1 year |
|
|
|
| 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) | Includes only treated patients experiencing severe oral mucositis. | Posted | Mean | Standard Deviation | Gy | Up to 1 year |
|
|
|
| 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. | Includes only treated patients experiencing severe oral mucositis. | Posted | Median | 95% Confidence Interval | days | Up to 1 year |
|
|
|
| Secondary | Percentage of Participants With Feeding Tube Replacement | Percentage of participants who require feeding tube placement during treatment. | Treated patients who required feeding tube placement. | Posted | Number | 90% Confidence Interval | percentage of participants | Up to 1 year |
|
|
|
| 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. | Treated patients experiencing trismus. | Posted | Number | 90% Confidence Interval | percentage of participants | Up to 1 year |
|
|
|
| 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. | Treated patients that completed Fact QoL assessments. | Posted | Median | Inter-Quartile Range | score on a scale | Up to 1 year |
|
|
|
| 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. | Treated patients experiencing oral mucositis. | Posted | Number | 90% Confidence Interval | percentage of participants | Up to 1 year |
|
|
|
| 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. | Posted | Number | 90% Confidence Interval | percentage of participants | Up to 1 year |
|
|
|
| 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. | Treated patients experiencing xerostomia. | Posted | Number | 90% Confidence Interval | percentage of participants | Up to 1 year |
|
|
|
| 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). | Treated patients experiencing dysgeusia. | Posted | Number | 90% Confidence Interval | percentage of participants | Up to 1 year |
|
|
|
| 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). | Treated patients experiencing radiodermatitis. | Posted | Number | 90% Confidence Interval | percentage of participants | Up to 1 year |
|
|
|
| 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. | Treated patients experiencing mouth pain. | Posted | Number | 90% Confidence Interval | percentage of participants | Up to 1 year |
|
|
|
| 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. | Treated patients experiencing throat pain. | Posted | Number | 90% Confidence Interval | percentage of participants | Up to 1 year |
|
|
|
| Secondary | Narcotic Analgesia Use | Percentage of patients using narcotic analgesia during treatment. | Treated patients that used a narcotic analgesic. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 2 years |
|
|
|
| Secondary | Breaks in Chemoradiotherapy | Mean number of breaks in chemoradiotherapy with LLLT use. | Treated patients that experienced breaks in chemoradiotherapy. | Posted | Mean | Standard Deviation | events | Up to 2 years |
|
|
|
| 7 |
| 47 |
| 18 |
| 47 |
| 47 |
| 47 |
| dysphagia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| dry mouth | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| dermatitis | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| dysphagia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| dry mouth | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| dysgeusia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| dermatitis | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| oral pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D009057 |
| Stomatognathic Diseases |
|
| FUNCTIONAL WELL BEING (FWB) |
|
| FACT-G total score (FACTG) |
|
| FACT HN |
|
| FACT-G with FACT HN total score |
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| FACT Head & Neck Trial Outcome Index |
|