Study for Dexamethasone Mouthwash in Lowering Episodes of Oral Mucositis Among Patients With Cancer: The SMILE Study
Phase: PHASE4
Conditions: Oral Mucositis Due to Chemotherapy
Sponsor: Woman's

Version Date: 11/11/2025 
 
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Study for Dexamethasone Mouthwash in Lowering 
Episodes of Oral Mucositis among Patients with Cancer: 
The SMILE Study 
Sponsor: Foundation for Woman’s  
 
Principal Investigators:  J. Hunter Collins, PhD 
 
 
 
Mary R. Salario, BSN, RN, CRN  
                                           Woman’s Hospital 
 
 
 
100 Woman’s Way, Baton Rouge, LA 70817 
                                             
 
 
Medical Investigator:  Lauren A. Zatarain, MD 
Louisiana Hematology Oncology Associates 
                                   
4950 Essen Lane Suite 500, Baton Rouge, LA 70809 
 
 
   
Co-Investigators:            Brooke Coogan, MS 
                                           Elizabeth Sutton, PhD 
                                           Woman’s Hospital 
                                           100 Woman’s Way, Baton Rouge, LA 70817 
 
                                            
 
 
 

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I. Table of Contents 
I. 
Background .................................................................................................................... 3 
II. 
Study Objectives ............................................................................................................. 3 
III. 
Study Design ............................................................................................................... 3 
a. 
Endpoints ...............................................................................................................................4 
b. 
Subject Population ..................................................................................................................4 
c. 
Eligibility criteria .....................................................................................................................4 
Inclusion criteria: .................................................................................................................................................. 4 
Exclusion criteria: .................................................................................................................................................. 4 
d. 
Study Timeline and Procedures ...............................................................................................5 
IV. 
Recruitment ................................................................................................................ 5 
a. 
Recruitment Process: ..............................................................................................................5 
b. 
Partial Waiver of HIPAA Authorization:....................................................................................5 
V. Consent Process .............................................................................................................. 5 
a. 
Informed Consent Process .......................................................................................................5 
b. 
Consent Procedures ................................................................................................................6 
VI. 
Risks ........................................................................................................................... 6 
VII. 
Benefits ....................................................................................................................... 6 
a. 
Possible Direct Benefits: ..........................................................................................................6 
b. 
Possible Indirect Benefits: .......................................................................................................6 
VIII. 
Withdrawal of Participation and Subject Complaints ................................................... 7 
IX. 
Compensation to Research Subjects ............................................................................. 7 
X. 
Sponsorship and Cost to Subjects .................................................................................... 7 
XI. 
Data ............................................................................................................................ 7 
a. 
Statistical Analysis Plan ...........................................................................................................7 
b. 
How records/data will be kept confidential .............................................................................8 
c. 
Data usage and sharing of Results with participants .................................................................8 
XII. 
Adverse Events Management and Data Safety Monitoring .......................................... 8 
XIII. 
References .................................................................................................................. 9 
 
 
 
 

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I. Background 
Oral mucositis, or chemotherapy-induced stomatitis, can be a side effect of cancer therapies, 
including cytotoxic chemotherapy and targeted treatments such as mechanistic target of rapamycin 
(mTOR) inhibitors. In patients with breast and/or gynecologic cancer, especially those receiving 
anthracycline-based chemotherapy or everolimus-based regimens, severe oral mucositis can adversely 
affect quality of life and treatment continuity. 
Recent research has shown that topical corticosteroids, specifically dexamethasone mouthwash, 
may reduce the incidence and severity of this condition. The SWISH trial, a phase 2 study in women 
undergoing everolimus and exemestane treatment for metastatic breast cancer, found that prophylactic 
use of dexamethasone mouthwash reduced the incidence of grade ≥2 oral mucositis (2% compared to 
33% in historical controls), resulting in fewer treatment interruptions and improved tolerability.1 
Another group conducted a randomized controlled trial in patients with early-stage breast cancer 
receiving anthracycline-based chemotherapy and found that dexamethasone mouthwash reduced the 
incidence of moderate-to-severe oral mucositis by 17% compared to controls.2 
Despite these results, questions remain regarding optimal dosing schedules, prophylactic versus 
reactive use, and generalizability across cancer subtypes and treatment protocols. The MIST trial, which 
compared prophylactic versus reactive dexamethasone administration, was underpowered but pointed 
to the importance of timing in maximizing benefit.3 Other observational studies and reviews advocate 
for proactive, standardized interventions that integrate corticosteroid rinses into clinical workflows.4-6 
The current study proposes to evaluate the prophylactic efficacy and tolerability of dexamethasone 
mouthwash in patients with cancer undergoing chemotherapy at Woman’s Cancer Pavilion. Given the 
safety profile and patient acceptability reported in prior trials, we hypothesize that dexamethasone 
mouthwash will reduce the incidence and severity of oral mucositis in this population compared to 
historical rates.  
 
II. Study Objectives 
• 
To evaluate the efficacy of prophylactic dexamethasone mouthwash in reducing the incidence of 
grade ≥2 oral mucositis in patients with cancer receiving chemotherapy regimens known to be 
associated with oral mucositis, including anthracyclines and taxanes. 
• 
To assess the severity of oral mucositis symptoms (graded per CTCAE criteria) in patients using 
dexamethasone mouthwash compared to historical controls 
• 
To evaluate the impact of oral mucositis on treatment adherence, including chemotherapy dose 
modifications, delays, or discontinuations, and on patient quality of life using the Oral Mucositis 
Weekly Questionnaire (OMWQ) 
 
III. Study Design 
This is a single-arm prospective study utilizing a historical comparison group to evaluate the 
effectiveness of prophylactic dexamethasone mouthwash in reducing oral mucositis among patients 
with cancer receiving chemotherapy associated with an increased risk of oral mucositis.  
 
Prospective Intervention Group: At least 45 patients with cancer scheduled to receive 
chemotherapy (e.g., anthracyclines, taxanes) at Woman’s Cancer Pavilion will be prospectively enrolled. 
Participants will receive a standardized dexamethasone mouthwash protocol (e.g., 10mL alcohol free 
dexamethasone 0.5 mg per 5mL oral solutions; swish for 2 minutes then spit; 4 times daily for 8 weeks; 
can continue to additional 8 weeks if clinically indicated) initiated the first week of chemotherapy and 
continued throughout the first chemotherapy cycle, or longer, depending on the regimen. Participants 
will be monitored for the development and severity of oral mucositis, mouthwash adherence, adverse 
events, and chemotherapy treatment modifications. They will also be given a survey (OMWQ) to 

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complete during their infusion appointments to assess the severity of mouth and throat soreness, pain, 
and how these symptoms affect daily activities such as eating, drinking, and speaking. 
Historical Control Group: The comparison group will consist of patients with cancer treated at 
Woman’s Cancer Pavilion with similar chemotherapy regimens, who did not receive prophylactic 
dexamethasone mouthwash. Retrospective data will be collected from electronic medical records, 
including demographic variables, chemotherapy regimen, incidence and grade of oral mucositis (as per 
CTCAE criteria), and treatment interruptions. 
a. Endpoints 
• 
Primary endpoint: Incidence of grade ≥2 oral mucositis during chemotherapy 
• 
Secondary endpoints: Oral mucositis severity, chemotherapy delays/reductions, adverse events 
related to mouthwash, patient-reported pain or discomfort, intervention adherence, OMWQ 
responses 
 
b. Subject Population 
The study will enroll at least 45 adult participants in the prospective intervention group. All participants 
will be patients with a confirmed cancer diagnosis who are scheduled to begin chemotherapy regimens 
known to be associated with oral mucositis, including anthracyclines and taxanes. 
• 
Number of Participants: 45 (prospectively enrolled for intervention group) 
• 
Age Range: ≥18 years (adult population only) 
• 
Health Status: Participants must have a confirmed cancer diagnosis and be healthy enough to 
receive chemotherapy. 
 
c. Eligibility criteria 
Inclusion criteria: 
• 
≥18 years old 
• 
Confirmed cancer diagnosis  
• 
Scheduled to receive or receiving chemotherapy known to be associated with oral mucositis (e.g., 
anthracyclines and taxanes) 
• 
Ability to provide informed consent  
• 
Ability to comply with study procedures 
 
Exclusion criteria: 
• 
Current tobacco usage or usage within the past 6 weeks. 
• 
HIV/AIDS 
• 
Gastrointestinal disorder (such as Crohn’s disease, ulcerative colitis, or celiac disease) 
• 
History of cold sores (herpes simplex virus) 
• 
Herpes zoster (oral shingles) within the past 6 weeks 
• 
Active oral infections at the time of enrollment (e.g., candidiasis) 
• 
Known sensitivity or allergy to dexamethasone 
• 
Inability to self-administer or tolerate mouthwash protocol 
• 
Concurrent enrollment in conflicting clinical trials 
• 
Existing oral ulcers or oral mucositis at enrollment 
• 
Pregnant 
• 
Uncontrolled diabetes mellitus as defined by HbA1c unknown or >8% in the past 3 months despite 
adequate therapy 

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d. Study Timeline and Procedures 
This study will span approximately 18 months and involve the prospective enrollment of at least 45 
patients with cancer scheduled to undergo chemotherapy. Participants will be followed for up to ten 
chemotherapy cycles, with additional follow-up if clinically indicated. The study will also include the use 
of a retrospective historical control group, which will not require direct participant involvement. 
 
IV. Recruitment  
Participants will be recruited through healthcare team referral within the Woman’s Cancer Pavilion or 
collaborating healthcare organization (e.g., Mary Bird Perkins and Our Lady of the Lake). Staff will 
identify potentially eligible patients based on diagnosis and treatment plan, and will introduce the study 
during clinical visits. If this referrer is not the patient’s medical oncologist, s/he will be contacted prior to 
recruitment to approve approaching their patient.  
 
a. Recruitment Process: 
• 
Healthcare Provider Identification: Healthcare providers will assess patients for preliminary 
eligibility. If the patient appears appropriate for the study, the physician will inform them of the 
research opportunity and/or provide their information to the study team for approach.  
• 
Study Introduction: A member of the research team (e.g., clinical research coordinator and/or nurse 
patient navigator) will contact potential participants to provide study details, answer questions, and 
conduct eligibility screening. 
• 
Informed Consent and HIPAA Authorization: Eligible patients who agree to participate will provide 
informed consent and HIPAA authorization before any study procedures begin.  
 
b. Partial Waiver of HIPAA Authorization: 
To facilitate identification of potentially eligible participants, the research and/or healthcare teams may 
review electronic medical records (EMRs). This process may involve access to limited protected health 
information (PHI), including contact information, diagnosis, chemotherapy regimen, and demographic 
information. 
• 
A partial waiver of HIPAA authorization is requested to allow screening of medical records prior to 
patient’s provision of HIPAA authorization. 
• 
PHI collected during screening will be used solely for the purpose of assessing eligibility. 
• 
PHI for individuals who are found to be ineligible or who decline participation will be destroyed and 
not retained for future use. 
• 
No study-specific procedures will be performed until the subject has documented consent and 
HIPAA authorization. 
 
V. Consent Process 
a. Informed Consent Process 
The process of obtaining, documenting, and maintaining informed consent will be conducted in 
accordance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) 
guidelines and the Declaration of Helsinki. An IRB-approved informed consent form (ICF) describing the 
study, study procedures, potential risks, and participant rights will be provided to each potential 
participant. Written informed consent must be obtained and documented prior to the initiation of any 
study-specific procedures. The participant will sign and date the ICF, and a copy will be provided to them 
for their records. Documentation of the consent process, including the date, will be maintained in the 
source documents. 

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Participants will be informed that their participation is entirely voluntary, that they may withdraw at any 
time without penalty or prejudice, and that refusal to participate will not affect the quality of their 
medical care. The rights and welfare of participants will be protected throughout the process. 
 
b. Consent Procedures 
The informed consent process will begin prior to enrollment and will continue throughout the duration 
of participation. The IRB-approved ICF will be provided to participants for review. Research staff will 
conduct the consent discussion, explain the study objectives, procedures, risks, and participant rights, 
and respond to any questions. A verbal explanation will be tailored to the participant’s level of 
comprehension. Participants will be afforded adequate time to review the document, ask questions, 
and, if they wish, consult with family members or legally authorized representatives before making a 
decision. 
 
VI. Risks 
Participants in this study may be exposed to minimal risks, primarily related to the use of 
dexamethasone mouthwash as an investigational prophylactic intervention. The risks associated with 
participation can be categorized as follows: 
• 
Oral side effects: The most commonly reported adverse event with dexamethasone mouthwash is 
oral candidiasis (thrush). A small number of participants may experience a burning or unpleasant 
taste during rinsing. 
• 
Steroid-related effects: Risks include minor alterations in blood glucose or local immune 
suppression within the oral cavity. 
 
VII. Benefits  
Participation in this study may offer direct clinical benefits to enrolled subjects, as well as potential 
indirect benefits to future patients and the broader medical community. 
 
a. Possible Direct Benefits: 
• 
Participants in the prospective arm of the study will receive dexamethasone mouthwash, which has 
been shown in previous clinical trials to reduce the incidence and severity of oral mucositis. 
• 
Preventing or lessening oral mucositis may result in improved comfort, nutritional intake, ability to 
communicate, and overall quality of life during chemotherapy treatment. 
• 
Reducing oral discomfort may also help participants complete their chemotherapy regimens without 
interruption, minimizing dose delays or reductions and potentially enhancing treatment efficacy. 
 
b. Possible Indirect Benefits: 
• 
Even if no direct clinical benefit is experienced, participants will contribute to important scientific 
knowledge about the prevention of oral mucositis in patients with cancer. 
• 
The findings may help refine supportive care practices and inform future standard-of-care 
interventions, especially for patients receiving taxane and/or anthracycline-based therapies. 
• 
Participants will also receive regular oral assessments and symptom monitoring, which may help 
identify and address oral complications promptly, regardless of their relationship to the study 
intervention. 
 

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VIII. Withdrawal of Participation and Subject Complaints 
Participants can request withdrawal from the study to research@womans.org or call the 
research department where removal of study data can be performed securely via REDCap database. 
Instructions for how to withdraw will be included in the study ICF. Upon receipt of withdrawal request, 
the record will be deleted from the REDCap database.  
Instructions to submit a research complaint along with contact information is posted on the 
main womans.org/research webpage, as well as included in the consent form: “You can also call the 
research office at Woman’s if you cannot reach the study team, have questions about your rights as a 
research participant, or want to speak to someone not directly involved with this study: call Ericka 
Seidemann, Human Protections Administrator, at 225-231-5296 or email research@womans.org.”. 
 
IX. Compensation to Research Subjects 
Patients will not be compensated for participation in this study.  
 
X. Sponsorship and Cost to Subjects 
The study costs are being paid by a grant from the Foundation for Woman’s.  
 
XI. Data  
a. Statistical Analysis Plan  
Data collected will be analyzed using standard statistical software (e.g., SPSS, R, or SAS). Descriptive 
statistics will be used to summarize demographic variables, cancer diagnosis, oral mucositis, etc. 
Continuous variables will be summarized using means and standard deviations; categorical variables will 
be reported as frequencies and percentages.  
 
This study will use identifiable information obtained from both prospectively enrolled 
participants and a retrospective historical control group. The data will be collected from clinical records 
and physician assessments. No biological specimens or genetic information will be collected or analyzed 
in this study. 
Prospective Cohort: For participants enrolled in the dexamethasone mouthwash intervention 
group, the following research materials will be collected: 
• 
Sociodemographic data: height, weight, race, ethnicity, date of birth, education, income, 
language spoken, health insurance type, etc. 
• 
Medical history and diagnosis: type and stage of cancer, comorbid conditions 
• 
Chemotherapy regimen: drug name, dose, schedule, start dates 
• 
Oral mucositis data: incidence, grade (using CTCAE criteria), duration of symptoms, OMWQ 
responses 
• 
Adverse event data: type, severity, timing, and relationship to mouthwash use 
• 
Mouthwash adherence: frequency and consistency of use (via self-report and staff monitoring) 
 
Historical Control Group: This group will include patients with cancer previously treated at 
Woman’s Cancer Pavilion who received standard chemotherapy without dexamethasone mouthwash. 
Data will be abstracted from the hospital’s electronic medical records (EMR), including but not limited 
to: 
• 
Demographic data: height, weight, race, ethnicity, date of birth, education, income, language 
spoken, health insurance type, etc. 
• 
Medical history and diagnosis: type and stage of cancer, comorbid conditions 
• 
Chemotherapy regimen: drug name, dose, schedule, start dates 
• 
Oral mucositis data: incidence, grade (using CTCAE criteria), and duration of symptoms 

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• 
Relevant adverse events or treatment delays due to oral mucositis 
 
b. How records/data will be kept confidential  
Protected health information (PHI) will not be used in publications resulting from information in the 
study. Study data, i.e. data extracted from the medical record, will be stored in REDCap or excel and will 
be accessible only through password-protected login and permissioned projects. The research team will 
have access to the data, and the Principal Investigator will be responsible for receipt and transmission of 
the data. All electronic records will be kept behind Woman’s Hospital firewalls in order to maintain 
security. Permission to use PHI collected in the study for future contact will be obtained from 
participants via the consent form and is strictly voluntary. Data will not be stored on portable devices, 
such as laptops or USBs. Protected Health Information (PHI) will not be used in any publications of the 
study results. 
 
c. Data usage and sharing of Results with participants  
The results of the study will be analyzed and published in a peer-reviewed medical journal, but no 
identifying data will be published. Individual nor aggregated results will not be shared with individual 
participants. A summary of the study results will be prepared in lay language for distribution to the 
study participants at the end of the trial and its analysis. 
 
XII. Adverse Events Management and Data Safety Monitoring 
Adverse event reporting will be limited to events that are reasonably related to the study intervention 
(dexamethasone mouthwash). Investigators will monitor for any local or systemic reactions that may 
result from the use of the mouthwash, including but not limited to allergic reactions or unexpected side 
effects. Only serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs), 
and serious adverse drug reactions (SADRs) that are deemed related to the study mouthwash will be 
reported to the Woman’s Hospital Foundation Institutional Review Board (IRB), in accordance with 
applicable federal regulations, local HRPP policies, and IRB requirements. We will collect the following 
information at minimum for each of these events: 
• 
Appropriate identifying information for the research protocol, such as the title, investigator’s 
name, and the IRB project number. 
• 
A detailed description of the adverse event, incident, experience, or outcome.  
• 
An explanation of the basis for determining that the adverse event, incident, experience, or 
outcome represents an unanticipated problem. 
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the unanticipated problem. 
To satisfy the requirement for prompt reporting, unanticipated problems will be reported using the 
following timeline:   
• 
Unanticipated problems that are serious adverse events will be reported to the IRB and the 
study coordinator within 2 business days of becoming aware of the event. 
• 
Any other unanticipated problem will be reported within 2 weeks of the investigator becoming 
aware of the problem. 
 
 
 

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XIII. References 
1. Rugo HS, Seneviratne L, Beck JT, et al. Prevention of everolimus-related stomatitis in women 
with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone 
mouthwash (SWISH): a single-arm, phase 2 trial. Lancet Oncol. 2017;18(5):654-662. 
doi:10.1016/S1470-2045(17)30109-2 
2. Kuba S, Maeda S, Shibata K, et al. Efficacy and safety of a dexamethasone-based mouthwash to 
prevent chemotherapy-induced stomatitis in women with breast cancer: a multicentre, open-
label, randomised phase 2 study. J Evid Based Dent Pract. 2023;23(3):101896. 
doi:10.1016/j.jebdp.2023.101896 
3. Ruddy KJ, Zahrieh D, He J, et al. Dexamethasone to prevent everolimus-induced stomatitis 
(Alliance MIST Trial: A221701). Semin Oncol. 2023;50(1-2):7-10. 
doi:10.1053/j.seminoncol.2023.01.001 
4. Kuderer NM, Desai A, Lustberg MB, Lyman GH. Mitigating acute chemotherapy-associated 
adverse events in patients with cancer. Nat Rev Clin Oncol. 2022;19(11):681-697. 
doi:10.1038/s41571-022-00685-3 
5. Seiler S, Kosse J, Loibl S, Jackisch C. Adverse event management of oral mucositis in patients 
with breast cancer. Breast Care (Basel). 2014;9(4):232-237. doi:10.1159/000366246 
6. Saigal B, Guerra L. Prevention of Stomatitis: Using Dexamethasone-Based Mouthwash to Inhibit 
Everolimus-Related Stomatitis. Clin J Oncol Nurs. 2018;22(2):211-217. doi:10.1188/18.CJON.211-
217