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

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00293462
• Other study ID #: CDR0000459510
• Secondary ID: UCSF-H452-26184-
• Status: Completed
• Phase: Phase 3
• Start date: June 7, 2005
• Est. completion date: December 31, 2009

Study information

• Verified date: July 2021
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: December 31, 2009
• Est. primary completion date: December 31, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms
• Mucositis
• Mucositis Oral
• Radiation Toxicity
• Stomatitis
• Tongue Cancer
• Tongue Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Marilyn Dodd	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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