Clinical trial NCT02123511: Acetylcysteine Rinse in Reducing Saliva Thickness and Mucositis in Patients With Head and Neck Cancer Undergoing Radiation Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-04-25
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility 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

Primary outcomes:
measure: Groningen Radiotherapy-Induced Xerostomia (GRIX) Sticky Saliva Total Score Area Under the Curve (AUC)
timeFrame: Up to 2 weeks following radiotherapy
Secondary outcomes:
measure: Groningen Radiotherapy-Induced Xerostomia (GRIX) Sticky Saliva Daytime Area Under the Curve (AUC)
timeFrame: Up to 90 days after completion of radiation therapy
measure: Groningen Radiotherapy-Induced Xerostomia (GRIX) Sticky Saliva Nighttime Area Under the Curve (AUC).
timeFrame: Up to 90 days after completion of radiation therapy
measure: GRIX Xerostomia Daytime AUC
timeFrame: Up to 90 days after completion of radiation therapy
measure: GRIX Xerostomia Nighttime AUC
timeFrame: Up to 90 days after completion of radiation therapy
measure: GRIX Xerostiomia Total Score AUC
timeFrame: Up to 90 days after completion of radiation therapy
measure: EORTC Quality of Life Questionnaire (QLQ) H&N Pain AUC
timeFrame: Up to 90 days after completion of radiation therapy
measure: EORTC Quality of Life Questionnaire (QLQ) Swallowing
timeFrame: Up to 90 days after completion of radiation therapy
measure: EORTC Quality of Life Questionnaire (QLQ) H&N Sticky Saliva AUC
timeFrame: Up to 90 days after completion of radiation therapy
measure: Adverse Event, as Measured by the Number of Patients With a Maximum Grade of Any Adverse Event
timeFrame: Up to 90 days after completion of radiation therapy
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Bismarck
country: United States
facility: Bismarck Cancer Center
state: North Dakota
city: Grand Forks
country: United States
facility: Altru Cancer Center
state: North Dakota
Study officials:
affiliation: Mayo Clinic
name: Michele Halyard
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sio TT, Blanchard MJ, Novotny PJ, Patel SH, Rwigema JM, Pederson LD, McGee LA, Gamez ME, Seeger GR, Martenson JA, Grover Y, Neben Wittich MA, Garces YI, Foote RL, Miller RC, Halyard MY. N-Acetylcysteine Rinse for Thick Secretion and Mucositis of Head and Neck Chemoradiotherapy (Alliance MC13C2): A Double-Blind Randomized Clinical Trial. Mayo Clin Proc. 2019 Sep;94(9):1814-1824. doi: 10.1016/j.mayocp.2019.03.031. Epub 2019 Aug 9.