Acetylcysteine Rinse in Reducing Saliva Thickness and Mucositis in Patients With Head and Neck Cancer Undergoing Radiation Therapy

Phase 2

Completed

Conditions: Recurrent Squamous Cell Carcinoma of the Nasopharynx
Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage I Verrucous Carcinoma of the Larynx
Mucositis
Recurrent Basal Cell Carcinoma of the Lip
Recurrent Mucoepidermoid Carcinoma of the Oral Cavity
Recurrent Salivary Gland Cancer
Recurrent Verrucous Carcinoma of the Larynx
Oral Complications
Recurrent Lymphoepithelioma of the Oropharynx

Interventions: Other: placebo
Drug: acetylcysteine
Other: quality-of-life assessment
Other: questionnaire administration

Registration Number: NCT02123511

Lead Sponsor: Mayo Clinic

Brief Summary: This randomized pilot clinical trial studies whether acetylcysteine oral rinse will lessen saliva thickness and painful mouth sores in patients with head and neck cancer undergoing radiation therapy. Side effects from radiation therapy to the head and neck, such as thickened saliva and mouth sores, may interfere with activities of daily living such as eating and drinking, and may also cause treatment to be stopped or delayed. Acetylcysteine rinse may reduce saliva thickness and mouth sores, and improve quality of life in patients with head and neck cancer undergoing radiation therapy.

Detailed Description: PRIMARY OBJECTIVES:

I. To determine the effectiveness of N-acetylcysteine (acetylcysteine) in improving saliva viscosity (as measured by the Groningen Radiotherapy-Induced Xerostomia \[GRIX\]) in patients undergoing chemotherapy and radiotherapy for head and neck cancer.

SECONDARY OBJECTIVES:

I. To determine whether N-acetylcysteine (NAC) can improve other GRIX subscale for patients undergoing chemotherapy and radiotherapy for head and neck cancer.

II. To determine whether NAC can improve patient reported quality of life as measured by the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire (QLQ) Head \& Neck (H\&N)35.

III. To assess the adverse event profile of NAC as measured by the Common Terminology Criteria for Adverse Events (CTCAE) every week during radiation.

IV. To determine patient adherence to N-acetylcysteine mucoadherent rinse using patient reported surveys.

V. To determine the long-term benefits of N-acetylcysteine as measured by the GRIX questionnaire at 45 days and 90 days post treatment.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive acetylcysteine oral rinse and gargle or swish for 60 seconds then spit 5 times per day, beginning within 3 days of the initiation of radiotherapy to 14 days following completion of radiotherapy.

ARM II: Patients receive a placebo oral rinse and gargle or swish for 60 seconds and then spit 5 times per day beginning within 3 days of the initiation of radiotherapy to 14 days following completion of radiotherapy.

After completion of study treatment, patients are followed up at 45 and 90 days.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 34

Inclusion Criteria

Histological confirmation of tumor of the oral cavity, oropharynx, supraglottic larynx, or nasopharynx
Receiving concurrent chemoradiotherapy/chemobiotherapy to a minimum dose equivalent to 60 Gy in 30 fractions in the adjuvant or definitive setting
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
Initiation of investigational agent =< 3 days after initiation of radiotherapy
Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
Ability to complete questionnaire(s) by themselves or with assistance
Provide informed written consent
Willing to return mail-in questionnaires during the observation phase of the study

Exclusion Criteria

Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Receipt of induction chemotherapy
Previous receipt of head and neck irradiation
Utilization of amifostine during radiotherapy
Greater than or equal to grade 2 dry mouth prior to chemoradiotherapy or greater than or equal to grade 2 mucositis
Previous intolerance/adverse effect/allergy to any component of the placebo or active agent
History of Sjogren's, lupus or scleroderma

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (acetylcysteine)	quality-of-life assessment	Patients receive acetylcysteine oral rinse and gargle or swish for 60 seconds then spit 5 times per day beginning within 3 days of the initiation of radiotherapy to 14 days following completion of radiotherapy.
Arm II (placebo)	questionnaire administration	Patients receive a placebo oral rinse and gargle or swish for 60 seconds and then spit 5 times per day beginning within 3 days of the initiation of radiotherapy to 14 days following completion of radiotherapy.
Arm II (placebo)	placebo	Patients receive a placebo oral rinse and gargle or swish for 60 seconds and then spit 5 times per day beginning within 3 days of the initiation of radiotherapy to 14 days following completion of radiotherapy.
Arm II (placebo)	quality-of-life assessment	Patients receive a placebo oral rinse and gargle or swish for 60 seconds and then spit 5 times per day beginning within 3 days of the initiation of radiotherapy to 14 days following completion of radiotherapy.
Arm I (acetylcysteine)	questionnaire administration	Patients receive acetylcysteine oral rinse and gargle or swish for 60 seconds then spit 5 times per day beginning within 3 days of the initiation of radiotherapy to 14 days following completion of radiotherapy.
Arm I (acetylcysteine)	acetylcysteine	Patients receive acetylcysteine oral rinse and gargle or swish for 60 seconds then spit 5 times per day beginning within 3 days of the initiation of radiotherapy to 14 days following completion of radiotherapy.

Primary Outcome Measures

Name	Time	Method
Groningen Radiotherapy-Induced Xerostomia (GRIX) Sticky Saliva Total Score Area Under the Curve (AUC)	Up to 2 weeks following radiotherapy	Groningen Radiotherapy-Induced Xerostomia (GRIX) sticky saliva total score Area under the curve (AUC).The GRIX questionnaire is a 14-item questionnaire with four subscales on 0-100 scales with higher scores representing worse symptoms. The aAUCpa for each subscale is calculated as the average of each AUC between each sequential assessment from treatment-initiation to the end of radiotherapy. For example; for each patient and each subscale, the subscale values at treatment-initiation and assessment-1 are used to calculate an Area Under the Curve (AUC) for that assessment time-period. Then these AUCs for all available assessment time-periods up to the end of their radiotherapy are averaged to yield the aAUCpa per patient per subscale. AUC will be calculated for each patient from baseline to two weeks following radiotherapy. The AUC values will be compared between the two arms using t-test (equal variance).

Secondary Outcome Measures

Name	Time	Method
Groningen Radiotherapy-Induced Xerostomia (GRIX) Sticky Saliva Nighttime Area Under the Curve (AUC).	Up to 90 days after completion of radiation therapy	Groningen Radiotherapy-Induced Xerostomia (GRIX) sticky saliva Nighttime Area under the curve (AUC).The GRIX questionnaire is a 14-item questionnaire with four subscales on 0-100 scales with higher scores representing worse symptoms. The aAUCpa for each subscale is calculated as the average of each AUC between each sequential assessment from treatment-initiation to the end of radiotherapy. For example; for each patient and each subscale, the subscale values at treatment-initiation and assessment-1 are used to calculate an Area Under the Curve (AUC) for that assessment time-period. Then these AUCs for all available assessment time-periods up to the end of their radiotherapy are averaged to yield the aAUCpa per patient per subscale. AUC will be calculated for each patient from baseline to two weeks following radiotherapy. The AUC values will be compared between the two arms using t-test (equal variance).
GRIX Xerostomia Daytime AUC	Up to 90 days after completion of radiation therapy	GRIX Xerostomia Daytime AUC. The GRIX questionnaire is a 14-item questionnaire with four subscales on 0-100 scales with higher scores representing worse symptoms. The aAUCpa for each subscale is calculated as the average of each AUC between each sequential assessment from treatment-initiation to the end of radiotherapy. For example; for each patient and each subscale, the subscale values at treatment-initiation and assessment-1 are used to calculate an Area Under the Curve (AUC) for that assessment time-period. Then these AUCs for all available assessment time-periods up to the end of their radiotherapy are averaged to yield the aAUCpa per patient per subscale. AUC will be calculated for each patient from baseline to two weeks following radiotherapy. The AUC values will be compared between the two arms using t-test (equal variance).
EORTC Quality of Life Questionnaire (QLQ) H&N Pain AUC	Up to 90 days after completion of radiation therapy	Average Area Under the Curve per assessment (aAUCpa) of QLQ H\&N35 subscales including pain, swallowing, teeth, opening mouth, dry mouth, sticky saliva, senses problems, coughing, speech problems, felt ill, trouble with social contact, trouble with social eating, less sexuality, pain killers, nutritional supplements, feeding tube, weight loss, and weight gain. The QLQ H\&N35 scoring algorithm was used for pain (questions 31-34) on 0-100 scales with higher scores representing worse symptoms. The aAUCpa for each subscale is calculated as the average of each AUC between each sequential assessment from treatment-initiation to the end of radiotherapy. For example; for each patient and subscale, the subscale values at treatment-initiation and assessment-1 are used to calculate an Area Under the Curve (AUC) for that assessment time-period. Then these AUCs for all available assessment time-periods up to the end of their radiotherapy are averaged to yield the aAUCpa per patient per subscale.
Groningen Radiotherapy-Induced Xerostomia (GRIX) Sticky Saliva Daytime Area Under the Curve (AUC)	Up to 90 days after completion of radiation therapy	Groningen Radiotherapy-Induced Xerostomia (GRIX) sticky saliva Daytime Area under the curve (AUC).The GRIX questionnaire is a 14-item questionnaire with four subscales on 0-100 scales with higher scores representing worse symptoms. The aAUCpa for each subscale is calculated as the average of each AUC between each sequential assessment from treatment-initiation to the end of radiotherapy. For example; for each patient and each subscale, the subscale values at treatment-initiation and assessment-1 are used to calculate an Area Under the Curve (AUC) for that assessment time-period. Then these AUCs for all available assessment time-periods up to the end of their radiotherapy are averaged to yield the aAUCpa per patient per subscale. AUC will be calculated for each patient from baseline to two weeks following radiotherapy. The AUC values will be compared between the two arms using t-test (equal variance).
GRIX Xerostomia Nighttime AUC	Up to 90 days after completion of radiation therapy	GRIX Xerostomia Nighttime AUC. The GRIX questionnaire is a 14-item questionnaire with four subscales on 0-100 scales with higher scores representing worse symptoms. The aAUCpa for each subscale is calculated as the average of each AUC between each sequential assessment from treatment-initiation to the end of radiotherapy. For example; for each patient and each subscale, the subscale values at treatment-initiation and assessment-1 are used to calculate an Area Under the Curve (AUC) for that assessment time-period. Then these AUCs for all available assessment time-periods up to the end of their radiotherapy are averaged to yield the aAUCpa per patient per subscale. AUC will be calculated for each patient from baseline to two weeks following radiotherapy. The AUC values will be compared between the two arms using t-test (equal variance).
EORTC Quality of Life Questionnaire (QLQ) Swallowing	Up to 90 days after completion of radiation therapy	Average Area Under the Curve per assessment (aAUCpa) of QLQ H\&N35 subscales including pain, swallowing, teeth, opening mouth, dry mouth, sticky saliva, senses problems, coughing, speech problems, felt ill, trouble with social contact, trouble with social eating, less sexuality, pain killers, nutritional supplements, feeding tube, weight loss, \& weight gain. The QLQ H\&N35 scoring algorithm was used for swallowing (questions 35-38) on 0-100 scales with higher scores representing worse symptoms. The aAUCpa for each subscale is calculated as the average of each AUC between each sequential assessment from treatment-initiation to the end of radiotherapy. For example; for each patient \& subscale, the subscale values at treatment-initiation \& assessment-1 are used to calculate an Area Under the Curve (AUC) for that assessment time-period. Then these AUCs for all available assessment time-periods up to the end of their radiotherapy are averaged to yield the aAUCpa per patient per subscale.
EORTC Quality of Life Questionnaire (QLQ) H&N Sticky Saliva AUC	Up to 90 days after completion of radiation therapy	Average Area Under the Curve per assessment (aAUCpa) of QLQ H\&N35 subscales including pain, swallowing, teeth, opening mouth, dry mouth, sticky saliva, senses problems, coughing, speech problems, felt ill, trouble with social contact, trouble with social eating, less sexuality, pain killers, nutritional supplements, feeding tube, weight loss, \& weight gain. The QLQ H\&N35 scoring algorithm was used for sticky saliva (question 42) on 0-100 scales with higher scores representing worse symptoms. The aAUCpa for each subscale is calculated as the average of each AUC between each sequential assessment from treatment-initiation to the end of radiotherapy. For example; for each patient \& subscale, the subscale values at treatment-initiation \& assessment-1 are used to calculate an Area Under the Curve (AUC) for that assessment time-period. Then these AUCs for all available assessment time-periods up to the end of their radiotherapy are averaged to yield the aAUCpa per patient per subscale.
Adverse Event, as Measured by the Number of Patients With a Maximum Grade of Any Adverse Event	Up to 90 days after completion of radiation therapy	The maximum grade for each type of toxicity will be recorded for each patient. The overall adverse event rates (percentages) for adverse events are reported below.
GRIX Xerostiomia Total Score AUC	Up to 90 days after completion of radiation therapy	GRIX Xerostiomia Total Score AUC. The GRIX questionnaire is a 14-item questionnaire with four subscales on 0-100 scales with higher scores representing worse symptoms. The aAUCpa for each subscale is calculated as the average of each AUC between each sequential assessment from treatment-initiation to the end of radiotherapy. For example; for each patient and each subscale, the subscale values at treatment-initiation and assessment-1 are used to calculate an Area Under the Curve (AUC) for that assessment time-period. Then these AUCs for all available assessment time-periods up to the end of their radiotherapy are averaged to yield the aAUCpa per patient per subscale. AUC will be calculated for each patient from baseline to two weeks following radiotherapy. The AUC values will be compared between the two arms using t-test (equal variance).

Trial Locations

Locations (5): Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Mayo Clinic
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Rochester, Minnesota, United States
State University of New York Upstate Medical University
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Syracuse, New York, United States
Bismarck Cancer Center
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Bismarck, North Dakota, United States
Altru Cancer Center
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Grand Forks, North Dakota, United States