Clinical trial NCT03982537: Effect of N-Acetyl Cysteine (NAC) on the Oral Microbiome
Official title: Effect of N-Acetyl Cysteine (NAC) on the Oral Microbiome and on the Degree of Mucositis Developed in Response to Concurrent Chemotherapy and Radiotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: Head and neck squamous cell cancer
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-06-11
Enrollment: 0
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 is a Phase II treatment, randomized 3:1 ratio, open label clinical trial to study the effect of short duration administration of N-acetyl cysteine on oral microbiome and on mucositis caused by concurrent chemotherapy and radiotherapy.

Detailed description: Primary Objective(s) I. To determine whether short duration pre-treatment with N-acetyl cysteine reduces the rate of severe mucositis that develops during the standard concurrent chemoradiotherapy in patients with locally advanced Head and Neck Squamous Cell Cancer.

Secondary Objective(s) I. Identify the effect of N-acetyl cysteine on the oral microbiome.

II. Identify the effect of short duration pre-treatment with N-acetyl cysteine on the duration and delay onset of severe radiation-induced mucositis developed during the standard concurrent chemoradiotherapy in patients with locally advanced Head and Neck Squamous Cell Cancer.

III. Bank saliva and blood for future studies of biomarkers that will be correlated with changes in the oral microbiome and the duration of mucositis.

IV. Determine if there is any effect of short duration pre-treatment with N-acetyl cysteine on tumor response to standard CRT as measured within the first year of treatment.

V. Determine the relationship between human papillomavirus status and smoking status and the baseline microbiome as well as well as the possible differential effect of N-acetyl cysteine on the structure of the oral microbiome in human papillomavirus positive patients vs smokers.

VI. Gather data on the incidence, severity, duration and onset of severe radiation-induced mucositis as well as data on saliva and blood biomarkers and evaluation of the oral microbiome in patients receiving standard of care primary or adjuvant chemoradiotherapy to gather preliminary data for use in designing future Phase 3 studies.

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically or cytologically confirmed HNSCC.
* Patients must be scheduled for definitive or adjuvant concurrent drug therapy and radiotherapy to include the oral cavity in the field and have a window of at least 14 days between the treatment decision and beginning of treatment.
* Patients must be ≥ 18 years old.
* Willing to provide consent for collection of samples of blood and saliva as scheduled through the treatment.
* Subject is willing and able to comply with the protocol for the duration of the study.
* Ability to understand and the willingness to sign an IRB-approved informed consent document.

Exclusion Criteria:

* Patients who have used NAC as a supplement or as a treatment within the last 6 months.
* Patients who have participated in another clinical study with an investigational product during the last 8 weeks.
* Receipt of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) within the last 8 weeks.
* Patients who are unable to swallow pills.
* Patients Patient is on medications that need to be continued and that might interact with NAC.
* Uncontrolled pre-existent illness of the digestive tract such as PUD, GERD.
* Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

Primary outcomes:
measure: Reduction in Severe Mucositis with Pre-treatment N-acetyl cysteine
timeFrame: 3 months post treatment
Secondary outcomes:
measure: Effects of N-acetyl cysteine on oral microbiome
timeFrame: At baseline and one year post treatment
measure: Effects of standard of care chemoradiotherapy on oral microbiome
timeFrame: At baseline and one year post treatment
measure: Number of Incidences of Severe Mucositis on N-acetyl cysteine
timeFrame: One year post treatment
measure: Number of Incidences of Severe Mucositis with Standard of Care Chemoradiotherapy
timeFrame: One year post treatment
measure: Number of Participants with Change in Saliva Biomarkers - N-acetyl cysteine
timeFrame: At baseline and one year post treatment
measure: Number of Participants with Change in Saliva Biomarkers - Standard of Care Chemoradiotherapy
timeFrame: At baseline and one year post treatment
measure: Number of Participants with Change in Blood Biomarkers - N-acetyl cysteine
timeFrame: At baseline and one year post treatment
measure: Number of Participants with Change in Blood Biomarkers - Standard of Care Chemoradiotherapy
timeFrame: At baseline and one year post treatment
measure: Tumor Response
timeFrame: One year post treatment
measure: Probability in Structure Changes of Microbiomes in Relation to Human Papillomavirus and Smoking Statuses and N-acetyl cysteine
timeFrame: One year post treatment
Other outcomes:
Locations:
Study officials:
affiliation: Wake Forest University Health Sciences
name: Mercedes Porosnicu, MD
role: PRINCIPAL_INVESTIGATOR
References: