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

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

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer; Radiation Toxicity; Tongue Cancer; Mucositis Oral
• Intervention / Treatment: Biological: sargramostim; Other: oral salt and soda mouthwash

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 Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Marilyn Dodd
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Marylin J. Dodd, RN, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 7, 2005
• Primary Completion (ACTUAL): December 31, 2009
• Study Completion (ACTUAL): December 31, 2009

Study Registration Dates

• First Submitted: February 16, 2006
• First Submitted That Met QC Criteria: February 16, 2006
• First Posted (ESTIMATE): February 17, 2006

Study Record Updates

• Last Update Posted (ACTUAL): July 30, 2021
• Last Update Submitted That Met QC Criteria: July 9, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: 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: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Mouth Neoplasms; Tongue Diseases; Head and Neck Neoplasms; Mucositis; Stomatitis; Tongue Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Sargramostim
• Other Study ID Numbers: CDR0000459510; UCSF-H452-26184-03 (OTHER: University of California, San Francisco); 02802 (OTHER: University of California, San Francisco); 5R01CA107080 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No