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

Overview

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.

Full Title of Study: “A Randomized, Double-Blind Pilot Study of N-Acetylcysteine Mucoadherent Rinse Versus Placebo for Thickened Secretions and Mucositis Secondary to Chemoradiotherapy in the Management of Head and Neck Malignancies”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Supportive Care
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: March 22, 2016

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.

Interventions

  • Drug: acetylcysteine
    • Oral rinse
  • Other: placebo
    • Oral rinse
  • Other: quality-of-life assessment
    • Ancillary studies
  • Other: questionnaire administration
    • Ancillary studies

Arms, Groups and Cohorts

  • Experimental: Arm I (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.
  • Placebo Comparator: Arm II (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.

Clinical Trial Outcome Measures

Primary Measures

  • Groningen Radiotherapy-Induced Xerostomia (GRIX) Sticky Saliva Total Score Area Under the Curve (AUC)
    • Time Frame: 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 Measures

  • Groningen Radiotherapy-Induced Xerostomia (GRIX) Sticky Saliva Daytime Area Under the Curve (AUC)
    • Time Frame: 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).
  • Groningen Radiotherapy-Induced Xerostomia (GRIX) Sticky Saliva Nighttime Area Under the Curve (AUC).
    • Time Frame: 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
    • Time Frame: 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).
  • GRIX Xerostomia Nighttime AUC
    • Time Frame: 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).
  • GRIX Xerostiomia Total Score AUC
    • Time Frame: 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).
  • EORTC Quality of Life Questionnaire (QLQ) H&N Pain AUC
    • Time Frame: 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.
  • EORTC Quality of Life Questionnaire (QLQ) Swallowing
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Mayo Clinic
  • Collaborator
    • National Cancer Institute (NCI)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Michele Halyard, Principal Investigator, Mayo Clinic

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