Head and Neck CancerPhase 2NCT03982537
Effect of N-Acetyl Cysteine (NAC) on the Oral Microbiome
A Phase 2 study testing N-Acetyl-L-Cysteine dietary supplement and Chemotherapy and Radiation in people with Head and Neck Cancer, run by Wake Forest University Health Sciences.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- N-Acetyl-L-Cysteine dietary supplement and Chemotherapy and Radiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 18 Jun 2020to 18 Jun 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
About this study
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
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.
Read the 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.
- 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.
- Conditions
- Head and Neck Cancer
- Being tested
- N-Acetyl-L-Cysteine dietary supplement, Chemotherapy and Radiation
- Keywords
- Head and neck squamous cell cancer
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-Acetyl-L-Cysteine dietary supplementDrug
Also called N-Acetyl-L-Cysteine
Treatment will be administered on an outpatient basis, either twice daily or 48 hours prior to starting chemotherapy radiation. Eligible participants will start NAC at least 9 days before definitive or adjuvant radiation therapy.
Chemotherapy and RadiationRadiation
Participants will receive definitive or adjuvant concurrent chemotherapy and radiotherapy s per standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Nature's Blend N-Acetyl-L-Cysteine 600 mg with Chemotherapy | Experimental | The treatment with NAC will be given twice daily for at least 10 days with the goal to cover the window of opportunity time between the treatment decision for CRT and the beginning of treatment (usually 14-21 days). Receives: Drug: N-Acetyl-L-Cysteine dietary supplement; Radiation: Chemotherapy and Radiation |
| Standard of Care Chemotherapy (CONTROL) | Other | Patients will receive definitive or adjuvant concurrent chemotherapy and radiotherapy as per standard of care Receives: Radiation: Chemotherapy and Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in Severe Mucositis with Pre-treatment N-acetyl cysteine
Severe mucositis will be defined as Grade III or IV mucositis as per WHO OM classification.
Measured: 3 months post treatment
Secondary outcomes (10)
Effects of N-acetyl cysteine on oral microbiome
Oral microbiome profiling will be determined using 16S rRNA gene sequencing to characterize the bacterial diversity and composition in the saliva collected from participants before and after treatment.
Measured: At baseline and one year post treatment
Effects of standard of care chemoradiotherapy on oral microbiome
Oral microbiome profiling will be determined using 16S rRNA gene sequencing to characterize the bacterial diversity and composition in the saliva collected from participants before and after treatment.
Measured: At baseline and one year post treatment
Number of Incidences of Severe Mucositis on N-acetyl cysteine
Time of development of mucositis grade III or above (marked as treatment day) and time of resolution below grade III (marked as post-treatment day) will be recorded and will serve to measure duration and delay onset of severe mucositis. For the time to event data, Kaplan Meier curves will be constructed to determine the median time to occurrence of severe mucositis.
Measured: One year post treatment
Number of Incidences of Severe Mucositis with Standard of Care Chemoradiotherapy
Time of development of mucositis grade III or above (marked as treatment day) and time of resolution below grade III (marked as post-treatment day) will be recorded and will serve to measure duration and delay onset of severe mucositis
Measured: One year post treatment
Number of Participants with Change in Saliva Biomarkers - N-acetyl cysteine
Banked saliva to describe biomarkers that could correlate with oral microbiome changes and with the severity of mucositis. Measurements that would be considered are evaluations of the nitrate reducing and NO producing capacity of oral bacteria, saliva H2S measurements and metabolic profiling of saliva.
Measured: At baseline and one year post treatment
Number of Participants with Change in Saliva Biomarkers - Standard of Care Chemoradiotherapy
Banked saliva to describe biomarkers that could correlate with oral microbiome changes and with the severity of mucositis. Measurements that would be considered are evaluations of the nitrate reducing and NO producing capacity of oral bacteria, saliva H2S measurements and metabolic profiling of saliva.
Measured: At baseline and one year post treatment
Number of Participants with Change in Blood Biomarkers - N-acetyl cysteine
Blood samples to describe biomarkers that could correlate with oral microbiome changes and with the severity of mucositis. Measurements that would be considered are evaluations of the nitrate reducing and NO producing capacity of oral bacteria, saliva H2S measurements and metabolic profiling of blood.
Measured: At baseline and one year post treatment
Number of Participants with Change in Blood Biomarkers - Standard of Care Chemoradiotherapy
Blood samples to describe biomarkers that could correlate with oral microbiome changes and with the severity of mucositis. Measurements that would be considered are evaluations of the nitrate reducing and NO producing capacity of oral bacteria, saliva H2S measurements and metabolic profiling of blood.
Measured: At baseline and one year post treatment
Tumor Response
Results of standard imaging studies and tumor response or progression will be collected from participant's electronic medical record and compared between participants pre-treated with N-acetyl cysteine and those no treated with N-acetyl cysteine.
Measured: One year post treatment
Probability in Structure Changes of Microbiomes in Relation to Human Papillomavirus and Smoking Statuses and N-acetyl cysteine
Human papillomavirus status and smoking status at baseline will be examined and microbiome data collected over time will be compared between each group (i.e. smokers vs non-smokers) and (HPV+ vs HPV-) and then with both groups combined (smoker/HPV+, smoker/HPV-, non-smoker/HPV+ and non-smoker/HPV-) for continuous measures that describe the microbiome measures, a repeated measures mixed model will be used to make these comparisons where participants will be considered as random effects and HPV status, smoking status and time (and their interactions) will be considered as fixed effects.
Measured: One year post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2019
- Study start18 Jun 2020
- Primary completion18 Jun 2020
- Study completion18 Jun 2020
Why it stopped: Concept is withdrawn and a different concept will be submitted the near future.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Mercedes Porosnicu, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03982537
- Sponsor's protocol ID
- IRB00058729
- Other IDs
- WFBCCC 97119, P30CA012197
- Status last verified
- Dec 2022
- First submitted
- 5 Jun 2019
- Last updated
- 19 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03982537
- Acronym / sponsor ID
- IRB00058729
- Conditions
- Head and Neck Cancer
- Keywords
- Head and neck squamous cell cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Concept is withdrawn and a different concept will be submitted the near future.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 18 Jun 2020 (actual)
- Primary completion
- 18 Jun 2020 (actual)
- Study completion
- 18 Jun 2020 (actual)
- First posted
- 11 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nature's Blend N-Acetyl-L-Cysteine 600 mg with Chemotherapy | Experimental | Drug: N-Acetyl-L-Cysteine dietary supplement, Radiation: Chemotherapy and RadiationThe treatment with NAC will be given twice daily for at least 10 days with the goal to cover the window of opportunity time between the treatment decision for CRT and the beginning of treatment (usually 14-21 days). |
| Standard of Care Chemotherapy (CONTROL) | Other | Radiation: Chemotherapy and RadiationPatients will receive definitive or adjuvant concurrent chemotherapy and radiotherapy as per standard of care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-Acetyl-L-Cysteine dietary supplementAlso: N-Acetyl-L-CysteineTreatment will be administered on an outpatient basis, either twice daily or 48 hours prior to starting chemotherapy radiation. Eligible participants will start NAC at least 9 days before definitive or adjuvant radiation therapy. | Drug | Nature's Blend N-Acetyl-L-Cysteine 600 mg with Chemotherapy |
| Chemotherapy and RadiationParticipants will receive definitive or adjuvant concurrent chemotherapy and radiotherapy s per standard of care. | Radiation | Nature's Blend N-Acetyl-L-Cysteine 600 mg with Chemotherapy, Standard of Care Chemotherapy (CONTROL) |
Primary outcome
Reduction in Severe Mucositis with Pre-treatment N-acetyl cysteine
Time frame: 3 months post treatment
Severe mucositis will be defined as Grade III or IV mucositis as per WHO OM classification.
10 secondary outcomes
Effects of N-acetyl cysteine on oral microbiome
Time frame: At baseline and one year post treatment
Effects of standard of care chemoradiotherapy on oral microbiome
Time frame: At baseline and one year post treatment
Number of Incidences of Severe Mucositis on N-acetyl cysteine
Time frame: One year post treatment
Number of Incidences of Severe Mucositis with Standard of Care Chemoradiotherapy
Time frame: One year post treatment
Number of Participants with Change in Saliva Biomarkers - N-acetyl cysteine
Time frame: At baseline and one year post treatment
Number of Participants with Change in Saliva Biomarkers - Standard of Care Chemoradiotherapy
Time frame: At baseline and one year post treatment
Number of Participants with Change in Blood Biomarkers - N-acetyl cysteine
Time frame: At baseline and one year post treatment
Number of Participants with Change in Blood Biomarkers - Standard of Care Chemoradiotherapy
Time frame: At baseline and one year post treatment
Tumor Response
Time frame: One year post treatment
Probability in Structure Changes of Microbiomes in Relation to Human Papillomavirus and Smoking Statuses and N-acetyl cysteine
Time frame: One year post treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mercedes Porosnicu, MD principal investigator
Wake Forest University Health Sciences
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing N-Acetyl-L-Cysteine dietary supplement and Chemotherapy and Radiation in people with Head and Neck Cancer, run by Wake Forest University Health Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in Severe Mucositis with Pre-treatment N-acetyl cysteine (time frame: 3 months post treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2022.