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

Sponsor
Mayo Clinic (Other)
Overall Status
Completed
CT.gov ID
NCT02123511
Collaborator
National Cancer Institute (NCI) (NIH)
34
Enrollment
5
Locations
2
Arms
51
Actual Duration (Months)
6.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: acetylcysteine
  • Other: placebo
  • Other: quality-of-life assessment
  • Other: questionnaire administration
 Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. 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:

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

  2. 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.

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

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

  5. 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
34 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Supportive Care
Official Title:
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
Actual Study Start Date :
Apr 1, 2014
Actual Primary Completion Date :
Mar 22, 2016
Actual Study Completion Date :
Jul 2, 2018

Arms and Interventions

Arm Intervention/Treatment
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.

Drug: acetylcysteine
Oral rinse
Other Names:
  • Airbron
  • Broncholysin
  • Brunac
  • N-acetylcysteine
  • NAC

    • Other: quality-of-life assessment
    Ancillary studies
    Other Names:
  • quality of life assessment

    • Other: questionnaire administration
    Ancillary studies
    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.

    Other: placebo
    Oral rinse
    Other Names:
  • PLCB

    • Other: quality-of-life assessment
    Ancillary studies
    Other Names:
  • quality of life assessment

    • Other: questionnaire administration
    Ancillary studies

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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).

    2. 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).

    3. 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).

    4. 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).

    5. 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).

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    Eligibility Criteria

    Criteria

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic in Arizona Scottsdale Arizona United States 85259
    2 Mayo Clinic Rochester Minnesota United States 55905
    3 State University of New York Upstate Medical University Syracuse New York United States 13210
    4 Bismarck Cancer Center Bismarck North Dakota United States 58501
    5 Altru Cancer Center Grand Forks North Dakota United States 58201

    Sponsors and Collaborators

    • Mayo Clinic
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Michele Halyard, Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT02123511
    Other Study ID Numbers:
    • MC13C2
    • NCI-2014-00865
    • Mod13-007632-07
    • MC13C2
    • P30CA015083
    First Posted:
    Apr 25, 2014
    Last Update Posted:
    Apr 30, 2019
    Last Verified:
    Dec 1, 2018
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Squamous Cell
    Laryngeal Neoplasms
    Carcinoma, Basal Cell
    Oropharyngeal Neoplasms
    Carcinoma, Verrucous
    Squamous Cell Carcinoma of Head and Neck
    Salivary Gland Neoplasms
    Nasopharyngeal Carcinoma
    Carcinoma, Adenoid Cystic
    Carcinoma, Mucoepidermoid
    Mucoepidermoid Tumor
    Tongue Neoplasms
    Mucositis
    Laryngeal Diseases
    Recurrence
    Acetylcysteine
    N-monoacetylcystine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm A (Placebo) Arm B (Rincinol)
    Arm/Group Description 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. 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.
    Period Title: Overall Study
    STARTED 18 16
    Eligible Patients 17 15
    COMPLETED 16 12
    NOT COMPLETED 2 4

    Baseline Characteristics

    Arm/Group Title Arm A (Placebo) Arm B (Rincinol) Total
    Arm/Group Description 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. 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. Total of all reporting groups
    Overall Participants 17 15 32
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55.9
    (10.3)
    60.9
    (10.3)
    58.3
    (10.4)
    Sex: Female, Male (Count of Participants)
    Female
    6
    35.3%
    4
    26.7%
    10
    31.3%
    Male
    11
    64.7%
    11
    73.3%
    22
    68.8%
    Region of Enrollment (Count of Participants)
    United States
    17
    100%
    15
    100%
    32
    100%

    Outcome Measures

    1. Primary Outcome
    Title Groningen Radiotherapy-Induced Xerostomia (GRIX) Sticky Saliva Total Score Area Under the Curve (AUC)
    Description 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).
    Time Frame Up to 2 weeks following radiotherapy

    Outcome Measure Data

    Analysis Population Description
    evaluable for Primary Endpoint (AUC for GRIX Sticky Saliva Total Score)
    Arm/Group Title Arm A (Placebo) Arm B (Rincinol)
    Arm/Group Description 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. 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.
    Measure Participants 16 12
    Mean (Standard Deviation) [score on a scale]
    40.9
    (23.7)
    27.2
    (21.0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Placebo), Arm B (Rincinol)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1232
    Comments
    Method t-test, 1 sided
    Comments
    2. Secondary Outcome
    Title Groningen Radiotherapy-Induced Xerostomia (GRIX) Sticky Saliva Daytime Area Under the Curve (AUC)
    Description 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).
    Time Frame Up to 90 days after completion of radiation therapy

    Outcome Measure Data

    Analysis Population Description
    evaluable for Primary Endpoint we included in this analysis.
    Arm/Group Title Arm A (Placebo) Arm B (Rincinol)
    Arm/Group Description 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. 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.
    Measure Participants 16 12
    Mean (Standard Deviation) [score on a scale]
    45.2
    (26.4)
    26.1
    (18.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Placebo), Arm B (Rincinol)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0422
    Comments
    Method t-test, 1 sided
    Comments
    3. Secondary Outcome
    Title Groningen Radiotherapy-Induced Xerostomia (GRIX) Sticky Saliva Nighttime Area Under the Curve (AUC).
    Description 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).
    Time Frame Up to 90 days after completion of radiation therapy

    Outcome Measure Data

    Analysis Population Description
    evaluable for Primary Endpoint we included in this analysis.
    Arm/Group Title Arm A (Placebo) Arm B (Rincinol)
    Arm/Group Description 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. 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.
    Measure Participants 16 12
    Mean (Standard Deviation) [score on a scale]
    34.5
    (22.8)
    29.1
    (26.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Placebo), Arm B (Rincinol)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5634
    Comments
    Method t-test, 1 sided
    Comments
    4. Secondary Outcome
    Title GRIX Xerostomia Daytime AUC
    Description 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).
    Time Frame Up to 90 days after completion of radiation therapy

    Outcome Measure Data

    Analysis Population Description
    Patients who completed the GRIX Xerostomia Daytime at all specified time points are included in this analysis.
    Arm/Group Title Arm A (Placebo) Arm B (Rincinol)
    Arm/Group Description 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. 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.
    Measure Participants 14 12
    Mean (Standard Deviation) [score on a scale]
    44.1
    (17.8)
    27.3
    (17.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Placebo), Arm B (Rincinol)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.02
    Comments
    Method t-test, 1 sided
    Comments
    5. Secondary Outcome
    Title GRIX Xerostomia Nighttime AUC
    Description 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).
    Time Frame Up to 90 days after completion of radiation therapy

    Outcome Measure Data

    Analysis Population Description
    Patients who completed the GRIX Xerostomia Nighttime at all specified time points are included in this analysis.
    Arm/Group Title Arm A (Placebo) Arm B (Rincinol)
    Arm/Group Description 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. 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.
    Measure Participants 16 12
    Mean (Standard Deviation) [score on a scale]
    39.8
    (16.4)
    31.3
    (19.6)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Placebo), Arm B (Rincinol)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.22
    Comments
    Method t-test, 1 sided
    Comments
    6. Secondary Outcome
    Title GRIX Xerostiomia Total Score AUC
    Description 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).
    Time Frame Up to 90 days after completion of radiation therapy

    Outcome Measure Data

    Analysis Population Description
    Patients who completed the GRIX Xerostomia Total Score at all specified time points are included in this analysis.
    Arm/Group Title Arm A (Placebo) Arm B (Rincinol)
    Arm/Group Description 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. 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.
    Measure Participants 14 12
    Mean (Standard Deviation) [score on a scale]
    43.8
    (14.7)
    28.5
    (17.6)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Placebo), Arm B (Rincinol)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.02
    Comments
    Method t-test, 1 sided
    Comments
    7. Secondary Outcome
    Title EORTC Quality of Life Questionnaire (QLQ) H&N Pain AUC
    Description 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.
    Time Frame Up to 90 days after completion of radiation therapy

    Outcome Measure Data

    Analysis Population Description
    Patients who completed the QLQ H&N Pain at all specified time points are included in this analysis.
    Arm/Group Title Arm A (Placebo) Arm B (Rincinol)
    Arm/Group Description 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. 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.
    Measure Participants 12 8
    Mean (Standard Deviation) [score on a scale]
    32.4
    (15.3)
    32.0
    (13.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Placebo), Arm B (Rincinol)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.95
    Comments
    Method t-test, 1 sided
    Comments
    8. Secondary Outcome
    Title EORTC Quality of Life Questionnaire (QLQ) Swallowing
    Description 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.
    Time Frame Up to 90 days after completion of radiation therapy

    Outcome Measure Data

    Analysis Population Description
    Patients who completed the QLQ H&N Swallowing at all specified time points are included in this analysis.
    Arm/Group Title Arm A (Placebo) Arm B (Rincinol)
    Arm/Group Description 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. 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.
    Measure Participants 10 8
    Mean (Standard Deviation) [score on a scale]
    34.7
    (18.8)
    22.3
    (17.6)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Placebo), Arm B (Rincinol)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.17
    Comments
    Method t-test, 1 sided
    Comments
    9. Secondary Outcome
    Title EORTC Quality of Life Questionnaire (QLQ) H&N Sticky Saliva AUC
    Description 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.
    Time Frame Up to 90 days after completion of radiation therapy

    Outcome Measure Data

    Analysis Population Description
    Patients who completed the QLQ H&N Sticky Saliva at all specified time points are included in this analysis.
    Arm/Group Title Arm A (Placebo) Arm B (Rincinol)
    Arm/Group Description 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. 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.
    Measure Participants 12 8
    Mean (Standard Deviation) [score on a scale]
    46.3
    (22.8)
    37.9
    (28.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Placebo), Arm B (Rincinol)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.48
    Comments
    Method t-test, 1 sided
    Comments
    10. Secondary Outcome
    Title Adverse Event, as Measured by the Number of Patients With a Maximum Grade of Any Adverse Event
    Description 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.
    Time Frame Up to 90 days after completion of radiation therapy

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A (Placebo) Arm B (Rincinol)
    Arm/Group Description 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. 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.
    Measure Participants 17 15
    Missing
    0
    0%
    1
    6.7%
    Grade 0
    2
    11.8%
    0
    0%
    Grade 1
    3
    17.6%
    5
    33.3%
    Grade 2
    4
    23.5%
    6
    40%
    Grade 3
    8
    47.1%
    3
    20%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Placebo), Arm B (Rincinol)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3824
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments

    Adverse Events

    Time Frame Adverse events are collected weekly during radiotherapy management visits
    Adverse Event Reporting Description Each CTCAE term is a unique representation of a specific event used for medical documentation and scientific analysis & is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who completed the AE form at least once. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and appear in the SAE table.
    Arm/Group Title Arm A (Placebo) Arm B (Rincinol)
    Arm/Group Description 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. 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.
    All Cause Mortality
    Arm A (Placebo) Arm B (Rincinol)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/17 (0%) 0/16 (0%)
    Serious Adverse Events
    Arm A (Placebo) Arm B (Rincinol)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/17 (29.4%) 0/16 (0%)
    Gastrointestinal disorders
    Dysphagia 1/17 (5.9%) 1 0/16 (0%) 0
    Nausea 1/17 (5.9%) 1 0/16 (0%) 0
    Oral hemorrhage 1/17 (5.9%) 1 0/16 (0%) 0
    Oral pain 1/17 (5.9%) 1 0/16 (0%) 0
    Infections and infestations
    Lung infection 1/17 (5.9%) 1 0/16 (0%) 0
    Investigations
    White blood cell decreased 1/17 (5.9%) 1 0/16 (0%) 0
    Nervous system disorders
    Dysgeusia 1/17 (5.9%) 1 0/16 (0%) 0
    Other (Not Including Serious) Adverse Events
    Arm A (Placebo) Arm B (Rincinol)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/17 (88.2%) 14/16 (87.5%)
    Gastrointestinal disorders
    Abdominal pain 5/17 (29.4%) 8 3/16 (18.8%) 6
    Dry mouth 1/17 (5.9%) 4 0/16 (0%) 0
    Dysphagia 1/17 (5.9%) 2 1/16 (6.3%) 1
    Mucositis oral 3/17 (17.6%) 6 3/16 (18.8%) 3
    Nausea 11/17 (64.7%) 28 7/16 (43.8%) 13
    Oral hemorrhage 4/17 (23.5%) 10 2/16 (12.5%) 7
    Oral pain 11/17 (64.7%) 47 8/16 (50%) 31
    Investigations
    Creatinine increased 1/17 (5.9%) 2 0/16 (0%) 0
    Weight loss 1/17 (5.9%) 1 0/16 (0%) 0
    Nervous system disorders
    Dysgeusia 1/17 (5.9%) 4 0/16 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 0/17 (0%) 0 1/16 (6.3%) 1
    Hoarseness 1/17 (5.9%) 3 0/16 (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.

    Results Point of Contact

    Name/Title Michele Halyard, M.D.; Robert Foote, M.D.
    Organization Mayo Clinic
    Phone 480-301-4567
    Email mhalyard@mayo.edu; foote.robert@mayo.edu
    Responsible Party:
    Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT02123511
    Other Study ID Numbers:
    • MC13C2
    • NCI-2014-00865
    • Mod13-007632-07
    • MC13C2
    • P30CA015083
    First Posted:
    Apr 25, 2014
    Last Update Posted:
    Apr 30, 2019
    Last Verified:
    Dec 1, 2018