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

• Sponsor: Marilyn Dodd (Other)
• Overall Status: Completed
• CT.gov ID: NCT00293462
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 91
• Location: 1
• Arms: 3
• Actual Duration (Months): 54.8
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer; Mucositis Oral; Radiation Toxicity; Tongue Cancer	Biological: sargramostim; Other: oral salt and soda mouthwash	Phase 3

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 91 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Management of Mucositis With GM-CSF (Sargramostim) Mouthwash Study Protocol
• Actual Study Start Date: Jun 7, 2005
• Actual Primary Completion Date: Dec 31, 2009
• Actual Study Completion Date: Dec 31, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I: GM-CSF Group (GG) 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
Active Comparator: Arm II: Salt & Soda Group (SS) 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; Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily.
Active Comparator: Arm III: Salt & Soda Switched to GM-CSF (SG) 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; Other: oral salt and soda mouthwash; Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily.

Outcome Measures

Primary Outcome Measures

1. Comparison of Number of Participants With Grade 1 or 2 Oral Mucositis (GM-CSF and SS Groups Only) [From baseline to onset of mucositis, approximately 16 days]

   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.

2. Comparison of the Mean Number of Days for Mucositis to Heal Across by Group [From onset of mucositis to healing of mucositis, approximately 80 days]

   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.

Secondary Outcome Measures

1. Comparison of the Combined Mean Score on the Overall Quality of Life Questionnaires by Group [Up to 3 months]

   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.

2. Comparison of Combined Mean Score on the Karnofsky Performance Status Scale (KPS) by Group [Up to 3 months]

   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.

3. Comparison of Combined Mean Score on the Pain Questionnaire by Group [Up to 3 months]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143

Sponsors and Collaborators

• Marilyn Dodd
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Marylin J. Dodd, RN, PhD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Marilyn Dodd, Principal Investigator, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00293462
• Other Study ID Numbers: CDR0000459510; UCSF-H452-26184-03; 02802; 5R01CA107080
• First Posted: Feb 17, 2006
• Last Update Posted: Jul 30, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Marilyn Dodd, Principal Investigator, University of California, San Francisco: 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
• Additional relevant MeSH terms: Head and Neck Neoplasms; Tongue Neoplasms; Mucositis; Stomatitis; Sargramostim

Study Results

Participant Flow

Recruitment Details	Adult (> 18 years of age) with confirmed histopathological diagnosis of head and neck carcinoma were recruited at the University of California, San Francisco Radiation Oncology Clinic, the Helen Diller Comprehensive Cancer Center, Saint Francis Medical Center in San Francisco, and Temple University Radiation Oncology Clinic in Philadelphia from May 2005 to Dec 2009.
Pre-assignment Detail	Of 532 potential subjects that were screened, 374 were excluded as they did not meet the inclusion criteria, 45 refused to participate and 22 were no-shows (declined radiation therapy), thereby reducing our original target sample population to 91.

Arm/Group Title	Arm I: GM-CSF Group (GG)	Arm II: Salt & Soda Group (SS)	Arm III: Salt & Soda Switched to GM-CSF (SG)
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	31	29	31
COMPLETED	24	21	19
NOT COMPLETED	7	8	12

Baseline Characteristics

Arm/Group Title	Arm I: GM-CSF Group (GG)	Arm II: Salt & Soda Group (SS)	Arm III: Salt & Soda Switched to GM-CSF (SG)	Total
Arm/Group Description	Arm I: Patients receive oral sargramostim (GM-CSF) mouthwash, holding it in their mouths and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.	Arm II: Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.	Arm II patients are split, with Arm III being switched to GM-CSF when they develop mucositis.	Total of all reporting groups
Overall Participants	31	29	31	91
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	25 80.6%	26 89.7%	26 83.9%	77 84.6%
>=65 years	6 19.4%	3 10.3%	5 16.1%	14 15.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.55 (13.73)	54.69 (12.22)	56.26 (11.29)	54.48 (12.43)
Sex: Female, Male (Count of Participants)
Female	11 35.5%	2 6.9%	11 35.5%	24 26.4%
Male	20 64.5%	27 93.1%	20 64.5%	67 73.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.2%	1 3.4%	2 6.5%	4 4.4%
Not Hispanic or Latino	30 96.8%	28 96.6%	27 87.1%	85 93.4%
Unknown or Not Reported	0 0%	0 0%	2 6.5%	2 2.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	10 32.3%	6 20.7%	5 16.1%	21 23.1%
Native Hawaiian or Other Pacific Islander	1 3.2%	0 0%	1 3.2%	2 2.2%
Black or African American	2 6.5%	4 13.8%	0 0%	6 6.6%
White	18 58.1%	16 55.2%	22 71%	56 61.5%
More than one race	0 0%	3 10.3%	0 0%	3 3.3%
Unknown or Not Reported	0 0%	0 0%	3 9.7%	3 3.3%

Outcome Measures

1. Primary Outcome

Title	Comparison of Number of Participants With Grade 1 or 2 Oral Mucositis (GM-CSF and SS Groups Only)
Description	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.
Time Frame	From baseline to onset of mucositis, approximately 16 days

Outcome Measure Data

Analysis Population Description

Intent to treat population consisted of randomized subjects who completed baseline questionnaire and had at least one dose of mouthwash

Arm/Group Title	Arm I: GM-CSF Group (GG)	Arm II: Salt & Soda Group (SS)
Arm/Group Description	Arm I: Patients receive oral sargramostim (GM-CSF) mouthwash, holding it in their mouths and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.	Arm II: Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.
Measure Participants	28	53
Number [participants]	28 90.3%	46 158.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: GM-CSF Group (GG), Arm II: Salt & Soda Group (SS)
	Comments	Fisher's exact two tailed test
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Fisher Exact
	Comments	Two by two table was used. One cell had expected frequency test less than five, so Fisher's exact two-tailed test was used.

2. Primary Outcome

Title	Comparison of the Mean Number of Days for Mucositis to Heal Across by Group
Description	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.
Time Frame	From onset of mucositis to healing of mucositis, approximately 80 days

Outcome Measure Data

Analysis Population Description

Intent to treat population consisted of randomized subjects who completed baseline questionnaire and had at least one dose of mouthwash

Arm/Group Title	Arm I: GM-CSF Group (GG)	Arm II: Salt & Soda Group (SS)	Arm III: Salt & Soda Switched to GM-CSF (SG)
Arm/Group Description	Arm I: Patients receive oral sargramostim (GM-CSF) mouthwash, holding it in their mouths and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.	Arm II: Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.	Arm II patients are split, with Arm III being switched to GM-CSF when they develop mucositis.
Measure Participants	28	21	19
Mean (Standard Deviation) [days]	81.5 (63.43)	79.4 (31.24)	77.4 (37.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: GM-CSF Group (GG), Arm II: Salt & Soda Group (SS), Arm III: Salt & Soda Switched to GM-CSF (SG)
	Comments	Kaplan-Meier estimate of the survival curves used information from subjects who develop mucositis to the healing of the mucositis in three groups, Group GG, SS, and SG. In order to compare the three curves that were created, the Mantel-Haenszel log-rank statistic was used
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	Mantel Haenszel
	Comments	Log rank, Breslow, Tarone-Ware test, but used mantel cox log rank for this analysis

3. Secondary Outcome

Title	Comparison of the Combined Mean Score on the Overall Quality of Life Questionnaires by Group
Description	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.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

Of the intent to treat population, subjects who did not fill out the baseline quality of life questionnaires were not included in our analysis.

Arm/Group Title	Arm I: GM-CSF Group (GG)	Arm II: Salt & Soda Group (SS)	Arm III: Salt & Soda Switched to GM-CSF (SG)
Arm/Group Description	Arm I: Patients receive oral sargramostim (GM-CSF) mouthwash, holding it in their mouths and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.	Arm II: Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.	Arm II patients are split, with Arm III being switched to GM-CSF when they develop mucositis.
Measure Participants	28	25	27
Mean (Standard Deviation) [score on a scale]	6.91 (1.59)	6.80 (1.46)	6.77 (1.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: GM-CSF Group (GG), Arm II: Salt & Soda Group (SS), Arm III: Salt & Soda Switched to GM-CSF (SG)
	Comments	Multilevel regression was used.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments	0.28 (quadratic)
	Method	Mixed Models Analysis
	Comments	Restricted Maximum Likelihood Methods with random intercepts was the only model used for the three groups and seven measurement time points.

4. Secondary Outcome

Title	Comparison of Combined Mean Score on the Karnofsky Performance Status Scale (KPS) by Group
Description	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.
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

Of the intent to treat population, subjects who did not fill out the baseline Karnofsky functional scales were not included in our analysis. They withdrew from the study after signing the consent forms for personal reasons.

Arm/Group Title	Arm I: GM-CSF Group (GG)	Arm II: Salt & Soda Group (SS)	Arm III: Salt & Soda Switched to GM-CSF (SG)
Arm/Group Description	Arm I: Patients receive oral sargramostim (GM-CSF) mouthwash, holding it in their mouths and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.	Arm II: Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.	Arm II patients are split, with Arm III being switched to GM-CSF when they develop mucositis.
Measure Participants	28	25	26
Mean (Standard Deviation) [score on a scale]	84.52 (12.61)	82.93 (10.92)	83.49 (12.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: GM-CSF Group (GG), Arm II: Salt & Soda Group (SS), Arm III: Salt & Soda Switched to GM-CSF (SG)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments	0.78 (quadratic)
	Method	Mixed Models Analysis
	Comments	Restricted Maximum Likelihood Methods with random intercepts was the only model used for the three groups and seven measurement time points.

5. Secondary Outcome

Title	Comparison of Combined Mean Score on the Pain Questionnaire by Group
Description	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
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

Of the intent to treat population, subjects who did not fill out the baseline pain questionnaires were not included in our analysis. They withdrew from the study after signing the consent forms for personal reasons.

Arm/Group Title	Arm I: GM-CSF Group (GG)	Arm II: Salt & Soda Group (SS)	Arm III: Salt & Soda Switched to GM-CSF (SG)
Arm/Group Description	Arm I: Patients receive oral sargramostim (GM-CSF) mouthwash, holding it in their mouths and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.	Arm II: Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.	Arm II patients are split, with Arm III being switched to GM-CSF when they develop mucositis.
Measure Participants	27	25	27
Mean (Standard Deviation) [score on a scale]	2.15 (2.40)	1.72 (2.26)	2.15 (2.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: GM-CSF Group (GG), Arm II: Salt & Soda Group (SS), Arm III: Salt & Soda Switched to GM-CSF (SG)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments	0.22 (quadratic)
	Method	Mixed Models Analysis
	Comments	Restricted Maximum Likelihood Methods with random intercepts was the only model used for the three groups and seven measurement time points.

Adverse Events

Time Frame	Up to 3 months
Adverse Event Reporting Description	Serious Adverse Events and adverse events were collected in the safety population which is comprised of all participants who were both randomized and received at least one dose of the study medication. Number of participants at risk represents the number of participants who received study medications.
Arm/Group Title	Arm I: GM-CSF Group (GG)		Arm II: Salt & Soda Group (SS)		Arm III: Salt & Soda Switched to GM-CSF (SG)
Arm/Group Description	Arm I: Patients receive oral sargramostim (GM-CSF) mouthwash, holding it in their mouths and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.		Arm II: Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily. Treatment continues during 6-7 weeks of radiotherapy and until the mucositis heals.		Arm II patients are split, with Arm III being switched to GM-CSF when they develop mucositis.
All Cause Mortality
	Arm I: GM-CSF Group (GG)		Arm II: Salt & Soda Group (SS)		Arm III: Salt & Soda Switched to GM-CSF (SG)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)		0/28 (0%)		0/28 (0%)
Serious Adverse Events
	Arm I: GM-CSF Group (GG)		Arm II: Salt & Soda Group (SS)		Arm III: Salt & Soda Switched to GM-CSF (SG)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)		2/28 (7.1%)		2/28 (7.1%)
Gastrointestinal disorders
Mucositis Oral	1/29 (3.4%)	1	0/28 (0%)	0	0/28 (0%)	0
Lower gastrointestinal hemorrhage	0/29 (0%)	0	1/28 (3.6%)	1	0/28 (0%)	0
General disorders
Other	0/29 (0%)	0	0/28 (0%)	0	1/28 (3.6%)	1
Immune system disorders
Allergic reaction	0/29 (0%)	0	1/28 (3.6%)	1	0/28 (0%)	0
Vascular disorders
Thromboembolic event	0/29 (0%)	0	0/28 (0%)	0	1/28 (3.6%)	1
Other (Not Including Serious) Adverse Events
	Arm I: GM-CSF Group (GG)		Arm II: Salt & Soda Group (SS)		Arm III: Salt & Soda Switched to GM-CSF (SG)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/29 (62.1%)		26/28 (92.9%)		27/28 (96.4%)
Blood and lymphatic system disorders
Transfusion	2/29 (6.9%)	2	0/28 (0%)	0	0/28 (0%)	0
Anemia	0/29 (0%)	0	0/28 (0%)	0	1/28 (3.6%)	1
Febrile neutropenia	1/29 (3.4%)	1	1/28 (3.6%)	1	1/28 (3.6%)	1
Cardiac disorders
Sinus Tachycardia	1/29 (3.4%)	1	0/28 (0%)	0	0/28 (0%)	0
Gastrointestinal disorders
Stomach pain	1/29 (3.4%)	1	0/28 (0%)	0	0/28 (0%)	0
Constipation	0/29 (0%)	0	0/28 (0%)	0	1/28 (3.6%)	1
General disorders
Fatigue	1/29 (3.4%)	1	1/28 (3.6%)	1	1/28 (3.6%)	1
Pain	0/29 (0%)	0	0/28 (0%)	0	1/28 (3.6%)	1
Other	0/29 (0%)	0	0/28 (0%)	0	1/28 (3.6%)	1
Infections and infestations
Wound infection	0/29 (0%)	0	0/28 (0%)	0	1/28 (3.6%)	1
Sinusitis	0/29 (0%)	0	1/28 (3.6%)	3	0/28 (0%)	0
Infection	0/29 (0%)	0	0/28 (0%)	0	1/28 (3.6%)	1
Injury, poisoning and procedural complications
Fall	1/29 (3.4%)	1	0/28 (0%)	0	0/28 (0%)	0
Radiation dermatitis	1/29 (3.4%)	1	1/28 (3.6%)	1	1/28 (3.6%)	4
Investigations
Weight loss	0/29 (0%)	0	0/28 (0%)	0	1/28 (3.6%)	1
Metabolism and nutrition disorders
Dehydration	5/29 (17.2%)	16	13/28 (46.4%)	27	10/28 (35.7%)	21
Musculoskeletal and connective tissue disorders
Exostosis	0/29 (0%)	0	1/28 (3.6%)	1	0/28 (0%)	0
Nervous system disorders
Ischemia Cerebrovascular	0/29 (0%)	0	0/28 (0%)	0	1/28 (3.6%)	1
Renal and urinary disorders
Acute kidney Injury	0/29 (0%)	0	1/28 (3.6%)	1	0/28 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/29 (3.4%)	1	1/28 (3.6%)	1	0/28 (0%)	0
Other	1/29 (3.4%)	1	0/28 (0%)	0	0/28 (0%)	0
Dyspnea	1/29 (3.4%)	1	0/28 (0%)	0	0/28 (0%)	0
Laryngopharyngeal Dyesthesia	0/29 (0%)	0	0/28 (0%)	0	1/28 (3.6%)	1
Laryngeal obstruction	0/29 (0%)	0	1/28 (3.6%)	1	0/28 (0%)	0
Laryngeal edema	0/29 (0%)	0	1/28 (3.6%)	1	0/28 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	1/29 (3.4%)	1	0/28 (0%)	0	0/28 (0%)	0
Rash acne form	0/29 (0%)	0	1/28 (3.6%)	2	1/28 (3.6%)	2
Surgical and medical procedures
Other	1/29 (3.4%)	1	0/28 (0%)	0	0/28 (0%)	0
Other	0/29 (0%)	0	0/28 (0%)	0	2/28 (7.1%)	2
Other	0/29 (0%)	0	0/28 (0%)	0	1/28 (3.6%)	1
Other	0/29 (0%)	0	1/28 (3.6%)	1	0/28 (0%)	0
Other	0/29 (0%)	0	1/28 (3.6%)	1	1/28 (3.6%)	1
Other	0/29 (0%)	0	1/28 (3.6%)	1	0/28 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.