GM-CSF Mouthwash for Preventing and Treating Mucositis in Patients Undergoing Radiation Therapy for Head and Neck Cancer

Study Overview
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Brief Summary
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GM-CSF may protect normal cells from the side effects, such as mucositis, of radiation therapy and may help damaged tissue heal faster after radiation therapy. This randomized clinical trial is studying how well GM-CSF works in preventing and treating mucositis in patients who are undergoing radiation therapy for head and neck cancer.

Detailed Description
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OBJECTIVES: Primary Compare the incidence of radiotherapy (RT)-induced oral mucositis of any grade, using the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria (RTOG ARMSC)-Mucous Membrane, in patients treated with 1 of 2 mouthwashes (sargramostim [GM-CSF] or salt and soda). (prevention portion of the study) Compare the effectiveness of the 2 mouthwashes in treating oral mucositis as defined by the incidence of RTOG ARMSC-Mucous Membrane grade 3 and 4 mucositis in patients in 1 of 3 groups (salt and soda, continuing GM-CSF, or new GM-CSF). (treatment portion of the study) Secondary Compare the effectiveness of the 2 mouthwashes in preventing RT-induced oral mucositis by the following direct indices: Cumulative RT dose prior to onset of oral mucositis (prevention portion only) Severity of RT-induced oral mucositis at onset and during treatment (using Oral Mucositis Assessment Scale (OMAS)) Severity of oral mucositis-related pain at onset and during treatment (using OMAS) Incidence of oral mucositis-related infection at onset and during treatment (using OMAS) Severity of oral mucositis-related problems with ingestion of food and fluids at onset and during treatment (using OMAS) Time to healing of RT-induced oral mucositis. Evaluate patients using the following indirect indices of oral mucositis morbidity during the prevention and treatment portions of the study. Tolerance to RT regimen Functional status Quality of life. OUTLINE: This is a multicenter, randomized, controlled, double-blinded study. Patients are stratified according to radiotherapy dose schedule (standard vs hyperfractionation vs intensity modulation) and concurrent chemotherapy (yes vs no). Prevention (no mucositis): Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral sargramostim (GM-CSF) mouthwash, holding it in their mouths and swallowing it in intervals over 1 hour once daily. Arm II: Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily. Treatment in both arms continues during 6-7 weeks of radiotherapy and/or the onset of mucositis. Patients also perform PRO-SELF: Mouth Aware (PSMA) twice daily. Treatment (onset of mucositis): Patients who are currently using GM-CSF mouthwash continue use as in prevention. Patients who are currently using salt and soda mouthwash are randomized to 1 of 2 treatment arms. Arm III: Patients receive GM-CSF mouthwash as in arm I. Arm IV: Patients receive salt and soda mouthwash as in arm II. In both arms, treatment continues until the mucositis heals. Patients perform PSMA four times daily during and for 3 months after radiotherapy. Quality of life is assessed at baseline and periodically after radiotherapy. After completion of study treatment, patients are followed every once a month for 3 months.

Official Title
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Management of Mucositis With GM-CSF (Sargramostim) Mouthwash Study Protocol

Conditions
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Head and Neck Cancer, Mucositis Oral, Radiation Toxicity, Tongue Cancer

Intervention / Treatment
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* Biological: sargramostim
* Other: oral salt and soda mouthwash


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histopathologically confirmed diagnosis of head and neck cancer Scheduled to undergo continuous course of conventional or hyperfractionated radiotherapy or intensity-modulated radiotherapy (IMRT) with or without concurrent chemotherapy Planning to receive a total radiation dose ≥ 5,500 centigray (cGy), administered in a single daily fraction of 180-220 cGy (5 days a week) or twice daily fractions of 110-150 cGy Normal baseline oral examinations (no pre-existing lesion) Karnofsky performance status 60-100% Mentally capable of participating in research protocol Expected survival > 4.5 months Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Creatinine ≤ 2.0 mg/dL Bilirubin ≤ 2.0 mg/dL Aspartate aminotransferase (AST) < 5 times upper limit of normal HIV negative Exclusion Criteria No unresolved adverse event from previous therapy No prior radiotherapy to the head and neck No prior or concurrent brachytherapy No prior participation in this study No T1 or T2 glottic tumors No other serious concurrent medical illness No history of insulin-dependent diabetes mellitus No prior hypersensitivity reaction to yeast material No recent history of oral ulceration, herpes simplex, oral candidiasis, severe gingivitis, active or chronic mucositis, or xerostomia No current New York Heart Association class II-IV congestive heart failure Not pregnant or nursing No chemotherapy, radiotherapy, or other investigational drugs within the past 4 weeks No major surgery within the past 2 weeks No systemic sargramostim (GM-CSF) within the past 7 days No systemic filgrastim (G-CSF) within the past 24 hours No systemic long-acting pegfilgrastim within the past 14 days No antibiotics, antifungals, or antivirals for oral conditions at baseline No other concurrent chemotherapy agent No concurrent enrollment on other head and neck studies No other concurrent investigational drugs No concurrent administration of any of the following: Magic or miracle mouthwash containing a palliative mixture of topical anesthetics/analgesics, coating agents, and other medications without an approved indication for topical oral use except liquid antacid formulations (e.g., Maalox® or Mylanta® or their generic equivalents) Other concurrent over-the-counter or prescription mouthwashes beyond the systematic oral care protocol provided by the study or any other drugs or agents to aid in oral hygiene (e.g., chlorhexidine, gluconate, pilocarpine, amifostine, sucralfate tablets or slurry, or benzydamine) Use of corticosteroids for chronic conditions OR within the past 7 days

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I: GM-CSF Group (GG)<br>Arm I: Patients were randomized to receive oral sargramostim (GM-CSF) mouthwash as a prevention, holding it in their mouths and swallowing it in intervals over 1 hour once daily. If they develop mucositis, they continue receiving GM-CSF treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals. | Biological: sargramostim<br> <br> |
| Active Comparator: Arm II: Salt & Soda Group (SS)<br>Arm II: Patients were randomized to receive salt and soda (SS) mouthwash as a prevention, holding it in their mouths and swallowing it in intervals over 1 hour once daily. If they develop mucositis, they continue receiving SS treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals. | Other: oral salt and soda mouthwash<br>* Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily.<br>|
| Active Comparator: Arm III: Salt & Soda Switched to GM-CSF (SG)<br>Arm III: Patients were randomized to receive oral salt and soda (SS) mouthwash as a prevention, holding it in their mouths and swallowing it in intervals over 1 hour once daily. If they develop mucositis, they continue receiving GM-CSF treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals. | Biological: sargramostim<br> <br> Other: oral salt and soda mouthwash<br>* Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Number of Participants With Grade 1 or 2 Oral Mucositis (GM-CSF and SS Groups Only) | The number of participants with recorded grade 1 (mild; Irritation, may experience slight pain, not requiring analgesic) or grade 2 (moderate; Patchy mucositis that may produce inflammatory serosanguinitis discharge; may experience moderate pain requiring analgesia) oral mucositis using the Radiation Therapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring Criteria Oral Mucosa Assessment Scale at baseline and during radiotherapy will be recorded. The RTOG grading is reliant on a clinician's ability to judge the anatomical changes associated with oral mucositis (size and characteristics of ulceration), with symptoms ranging from Grade 0 (no symptoms) to Grade 4 (Ulceration, hemorrhage, or necrosis). A comparison of incidence in the GM-CSF Group (GG) and Arm II: Salt & Soda Group (SS) will be reported. | From baseline to onset of mucositis, approximately 16 days | 
| Comparison of the Mean Number of Days for Mucositis to Heal Across by Group | The mean number of days for mucositis to heal will be used to evaluate the effectiveness of the two mouthwashes in treating oral mucositis as defined by the incidence of Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring. | From onset of mucositis to healing of mucositis, approximately 80 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the Combined Mean Score on the Overall Quality of Life Questionnaires by Group | Quality of life at baseline, during radiotherapy, and once a month for 3 months after radiotherapy. The items on the quality of life questionnaire developed for the study range in scores from 0-10 with higher scores indicating a better quality of life. Scores at all time points were combined to compute one mean score for overall quality of life during the study. | Up to 3 months | 
| Comparison of Combined Mean Score on the Karnofsky Performance Status Scale (KPS) by Group | Functional status of participants was measured by administering the KPS which contains items asking about performing daily activities. The scores are grouped in 10s ranging from 100 (Normal, no complaints) to 0 (Dead), with higher scores indicating better functional status. The KPS was administered at baseline, during radiotherapy, and once a month for 3 months after radiation therapy. Scores at all time points were combined to compute one mean to determine overall performance status during the course of the study. | Up to 3 months | 
| Comparison of Combined Mean Score on the Pain Questionnaire by Group | Severity and quality of pain was measured using a pain questionnaire developed for this study with total scores ranging from 0 (no pain) to 10 (most intense pain) with higher scores indicating a greater level of pain. The questionnaire was administered at baseline, during radiotherapy, and once a month for 3 months after radiotherapy. Scores at all time points were combined to compute one mean to determine overall pain intensity score during the course of the study | Up to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent squamous, basal cell carcinoma of the pharynx,larynx,lip, Oropharynx, paranasal sinus and nasal cavity, Stage I-IV lymphoepithelioma of the nasopharynx, Stage I-IV lymphoepithelioma of the oropharynx, Recurrent esthesioneuroblastoma of paranasal sinus, nasal cavity, Recurrent inverted papilloma of the paranasal sinus, nasal cavity, Recurrent midline granuloma of the paranasal sinus, nasal cavity, Untreated, current, metastatic squamous neck cancer, Recurrent verrucous carcinoma of the larynx, Recurrent lymphoepithelioma of the oropharynx, Stage I verrucous carcinoma of the larynx, Recurrent verrucous carcinoma of the oral cavity, Stage I verrucous carcinoma of the oral cavity, Stage II verrucous carcinoma of the larynx, Stage II verrucous carcinoma of the oral cavity, Stage III verrucous carcinoma of the larynx, Stage III verrucous carcinoma of the oral cavity, Stage IV verrucous carcinoma of the larynx, Stage IV verrucous carcinoma of the oral cavity, Recurrent adenoid cystic carcinoma of the oral cavity, Stage I adenoid cystic carcinoma of the oral cavity, Stage II adenoid cystic carcinoma of the oral cavity, Stage III adenoid cystic carcinoma of the oral cavity, Stage IV adenoid cystic carcinoma of the oral cavity, Recurrent mucoepidermoid carcinoma of the oral cavity, Stage I mucoepidermoid carcinoma of the oral cavity, Stage II mucoepidermoid carcinoma of the oral cavity, Stage III mucoepidermoid carcinoma of the oral cavity, Stage IV mucoepidermoid carcinoma of the oral cavity, Recurrent squamous cell carcinoma of the lip and oral cavity, Stage I squamous cell carcinoma of the lip and oral cavity, Stage II squamous cell carcinoma of the lip and oral cavity, Stage III squamous cell carcinoma of the lip and oral cavity, Stage IV squamous cell carcinoma of the lip and oral cavity