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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02123511
First received: April 23, 2014
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

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 Intervention
Mucositis
Oral Complications
Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
Recurrent Basal Cell Carcinoma of the Lip
Recurrent Lymphoepithelioma of the Nasopharynx
Recurrent Lymphoepithelioma of the Oropharynx
Recurrent Mucoepidermoid Carcinoma of the Oral Cavity
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Stage I Adenoid Cystic Carcinoma of the Oral Cavity
Stage I Basal Cell Carcinoma of the Lip
Stage I Lymphoepithelioma of the Nasopharynx
Stage I Lymphoepithelioma of the Oropharynx
Stage I Mucoepidermoid Carcinoma of the Oral Cavity
Stage I Salivary Gland Cancer
Stage I Squamous Cell Carcinoma of the Larynx
Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage I Squamous Cell Carcinoma of the Nasopharynx
Stage I Squamous Cell Carcinoma of the Oropharynx
Stage I Verrucous Carcinoma of the Larynx
Stage I Verrucous Carcinoma of the Oral Cavity
Stage II Adenoid Cystic Carcinoma of the Oral Cavity
Stage II Basal Cell Carcinoma of the Lip
Stage II Lymphoepithelioma of the Nasopharynx
Stage II Lymphoepithelioma of the Oropharynx
Stage II Mucoepidermoid Carcinoma of the Oral Cavity
Stage II Salivary Gland Cancer
Stage II Squamous Cell Carcinoma of the Larynx
Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage II Squamous Cell Carcinoma of the Nasopharynx
Stage II Squamous Cell Carcinoma of the Oropharynx
Stage II Verrucous Carcinoma of the Larynx
Stage II Verrucous Carcinoma of the Oral Cavity
Stage III Adenoid Cystic Carcinoma of the Oral Cavity
Stage III Basal Cell Carcinoma of the Lip
Stage III Lymphoepithelioma of the Nasopharynx
Stage III Lymphoepithelioma of the Oropharynx
Stage III Mucoepidermoid Carcinoma of the Oral Cavity
Stage III Salivary Gland Cancer
Stage III Squamous Cell Carcinoma of the Larynx
Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage III Squamous Cell Carcinoma of the Nasopharynx
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage III Verrucous Carcinoma of the Larynx
Stage III Verrucous Carcinoma of the Oral Cavity
Stage IV Lymphoepithelioma of the Nasopharynx
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity
Stage IVA Basal Cell Carcinoma of the Lip
Stage IVA Lymphoepithelioma of the Oropharynx
Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity
Stage IVA Salivary Gland Cancer
Stage IVA Squamous Cell Carcinoma of the Larynx
Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVA Squamous Cell Carcinoma of the Oropharynx
Stage IVA Verrucous Carcinoma of the Larynx
Stage IVA Verrucous Carcinoma of the Oral Cavity
Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity
Stage IVB Basal Cell Carcinoma of the Lip
Stage IVB Lymphoepithelioma of the Oropharynx
Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity
Stage IVB Salivary Gland Cancer
Stage IVB Squamous Cell Carcinoma of the Larynx
Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVB Squamous Cell Carcinoma of the Oropharynx
Stage IVB Verrucous Carcinoma of the Larynx
Stage IVB Verrucous Carcinoma of the Oral Cavity
Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity
Stage IVC Basal Cell Carcinoma of the Lip
Stage IVC Lymphoepithelioma of the Oropharynx
Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity
Stage IVC Salivary Gland Cancer
Stage IVC Squamous Cell Carcinoma of the Larynx
Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVC Squamous Cell Carcinoma of the Oropharynx
Stage IVC Verrucous Carcinoma of the Larynx
Stage IVC Verrucous Carcinoma of the Oral Cavity
Tongue Cancer
Drug: acetylcysteine
Other: placebo
Other: quality-of-life assessment
Other: questionnaire administration

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Area under the curve (AUC) of the GRIX sticky saliva total score [ Time Frame: Up to 2 weeks following radiotherapy ] [ Designated as safety issue: No ]
    Calculated for each patient from baseline to 2 weeks following radiotherapy. The AUC values will be compared between the two arms using either t-tests or Wilcoxon nonparametric tests and tested for normality using the Shapiro-Wilk test. If the normality assumption is rejected at a 0.20 level, Wilcoxon tests will be used to compare the AUC values between arms. If the normality assumption is not rejected, an F test will be used to compare the variances of the AUC values between the two arms at the 0.20 level.


Secondary Outcome Measures:
  • Scores for sticky saliva during the day, assessed using the GRIX subscale [ Time Frame: Up to 90 days after completion of radiation therapy ] [ Designated as safety issue: No ]
    AUCs will be compared using either t-tests (equal variance or unequal variance) or Wilcoxon nonparametric tests. Linear regression and repeated measures analyses will be done to adjust for confounding factors. Mean scores and 95% confidence intervals will be plotted over time by arm.

  • Scores for sticky saliva during the night, assessed using the GRIX subscale [ Time Frame: Up to 90 days after completion of radiation therapy ] [ Designated as safety issue: No ]
    AUCs will be compared using either t-tests (equal variance or unequal variance) or Wilcoxon nonparametric tests. Linear regression and repeated measures analyses will be done to adjust for confounding factors. Mean scores and 95% confidence intervals will be plotted over time by arm.

  • Scores for xerostomia during the day, assessed using the GRIX subscale [ Time Frame: Up to 90 days after completion of radiation therapy ] [ Designated as safety issue: No ]
    AUCs will be compared using either t-tests (equal variance or unequal variance) or Wilcoxon nonparametric tests. Linear regression and repeated measures analyses will be done to adjust for confounding factors. Mean scores and 95% confidence intervals will be plotted over time by arm.

  • Scores for xerostomia during the night, assessed using the GRIX subscale [ Time Frame: Up to 90 days after completion of radiation therapy ] [ Designated as safety issue: No ]
    AUCs will be compared using either t-tests (equal variance or unequal variance) or Wilcoxon nonparametric tests. Linear regression and repeated measures analyses will be done to adjust for confounding factors. Mean scores and 95% confidence intervals will be plotted over time by arm.

  • Xerostomia total scores, assessed using the GRIX subscale [ Time Frame: Up to 90 days after completion of radiation therapy ] [ Designated as safety issue: No ]
    AUCs will be compared using either t-tests (equal variance or unequal variance) or Wilcoxon nonparametric tests. Linear regression and repeated measures analyses will be done to adjust for confounding factors. Mean scores and 95% confidence intervals will be plotted over time by arm.

  • QLQ-H&N35 scores [ Time Frame: Up to 90 days after completion of radiation therapy ] [ Designated as safety issue: No ]
    Scores will be compared between the two arms


Estimated Enrollment: 36
Study Start Date: April 2014
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Experimental: 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 Name: PLCB
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02123511

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Michele Y. Halyard         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Miran J. Blanchard         
United States, New York
State University of New York Upstate Medical University Not yet recruiting
Syracuse, New York, United States, 13210
Contact: Jeffrey A. Bogart    315-464-5476    bogartj@upstate.edu   
Principal Investigator: Jeffrey A. Bogart         
United States, North Dakota
Bismarck Cancer Center Not yet recruiting
Bismarck, North Dakota, United States, 58501
Contact: Tarek A. Dufan    800-248-5511    tfischer@mohs.org   
Principal Investigator: Tarek A. Dufan         
Altru Cancer Center Not yet recruiting
Grand Forks, North Dakota, United States, 58201
Contact: Grant R. Seeger    701-780-6520    gseeger@altru.org   
Principal Investigator: Grant R. Seeger         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Michele Halyard, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT02123511     History of Changes
Other Study ID Numbers: MC13C2, NCI-2014-00865, MC13C2, P30CA015083
Study First Received: April 23, 2014
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Laryngeal Diseases
Carcinoma, Squamous Cell
Nasopharyngeal Neoplasms
Carcinoma, Basal Cell
Salivary Gland Neoplasms
Mucositis
Oropharyngeal Neoplasms
Carcinoma, Verrucous
Laryngeal Neoplasms
Carcinoma, Adenoid Cystic
Carcinoma, Mucoepidermoid
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Neoplasms, Basal Cell
Mouth Neoplasms
Mouth Diseases
Salivary Gland Diseases
Gastroenteritis
Gastrointestinal Diseases

ClinicalTrials.gov processed this record on September 16, 2014