Open-label, Phase II Study of Stomatitis Prevention With a Steroid-based Mouthwash in Post-menopausal Women With Estrogen-receptor-positive (ER+), Human Epidermal Growth Factor Receptor 2 (HER2)- Metastatic or Locally Advanced Breast Cancer
Condition: Advanced Breast Cancer
MeSH terms: Breast Neoplasms; Stomatitis
Intervention: Dexamethasone based mouthwash; Everolimus; Exemestane
Intervention description: Dexamethasone steroid-based oral solution, comprised of 0.5 milligrams per 5mL of alcohol-free dexamethasone.; Commercially available everolimus 10 mg was prescribed to participants by the Investigator according to local regulations.; Commercially available exemestane 25 mg was prescribed to participants by the Investigator according to local regulations.
Intervention MeSH terms: Dexamethasone; Everolimus; Exemestane
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 92.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Open-label, Phase II study of Stomatitis prevention with a steroid-based mouthwash in
      Post-menopausal women with ER+, HER2- Metastatic or Locally Advanced Breast Cancer
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult women > 18 years of age with metastatic or locally advanced breast cancer not
             amenable to curative treatment by surgery or radiotherapy

          2. Histological or cytological confirmation of hormone-receptor positive (HR+) human
             epidermal growth factor receptor 2 negative (HER2-) breast cancer

          3. Postmenopausal women. Postmenopausal status is defined either by:

               -  Age ≥ 55 years and one year or more of amenorrhea

               -  Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20
                  pg/ml

               -  Surgical menopause with bilateral oophorectomy

               -  Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone
                  (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for
                  induction of ovarian suppression

          4. Patient has been assessed by treating physician to be appropriate candidate for
             everolimus plus exemestane therapy as treatment of advanced or metastatic breast
             cancer and plans to prescribe everolimus 10mg PO QD in combination with exemestane
             25mg PO QD

          5. Patient must start everolimus 10mg plus exemestane 25mg treatment on Cycle 1 Day 1 of
             trial

          6. ECOG Performance status ≤ 2

          7. Adequate renal function: serum creatinine ≤ 1.5x ULN;

          8. Willingness to self-report level of oral pain using Visual Analog Scale (VAS) and the
             Normalcy Diet Scale (NDS) throughout each stomatitis event, as required in the patient
             diary. At baseline, patient's self-reported oral pain level, using VAS, must be 0 and
             the normalcy diet scale score should ≥ 60

          9. Signed informed consent obtained prior to any screening procedure

        Exclusion criteria:

          1. Patients currently receiving anticancer therapies (except biphosphonate, denosumab);

          2. Patients who currently have stomatitis/oral mucositis/mouth ulcers;

          3. Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g.
             sirolimus, temsirolimus);

          4. Known impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of oral Everolimus;

          5. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy.
             Patients with a known history of impaired fasting glucose or diabetes mellitus (DM)
             may be included, however blood glucose and antidiabetic treatment must be monitored
             closely throughout the trial and adjusted as necessary;

          6. Patients who have any severe and/or uncontrolled medical conditions such as:

               -  Unstable angina pectoris, symptomatic congestive heart failure, myocardial
                  infarction ≤6 months prior to start of everolimus, serious uncontrolled cardiac
                  arrhythmia, or any other clinically significant cardiac disease

               -  Symptomatic congestive heart failure of New York heart Association Class III or
                  IV

               -  active (acute or chronic) or uncontrolled severe infection, liver disease such as
                  cirrhosis, decompensated liver disease (except for Hep B and Hep C positive
                  patients)

               -  Known severely impaired lung function (spirometry and DLCO 50% or less of normal
                  and O2 saturation 88% or less at rest on room air)

               -  active, bleeding diathesis;

          7. Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or
             inhaled corticosteroids are allowed;

          8. Known history of HIV seropositivity;

          9. Patients who have received live attenuated vaccines within 1 week of start of
             everolimus and during the study. Patient should also avoid close contact with others
             who have received live attenuated vaccines. Examples of live attenuated vaccines
             include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever,
             varicella and TY21a typhoid vaccines;

         10. Patients who have a history of another primary malignancy, with the exceptions of:
             non-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from
             which the patient has been disease free for ≥3 years;

         11. Patients with a history of non-compliance to medical regimens or who are considered
             potentially unreliable or will not be able to complete the entire study or patient
             diaries;

         12. Patients who are currently part of any clinical investigation or who has not had
             resolution of all acute toxic effects or prior anti-cancer therapy to NCI CTCAE
             version 4.03 Grade 1 (except alopecia or other toxicities not considered a safety risk
             for the patient at investigator's discretion).