Mucoadhesive Oral Wound Rinse in Preventing and Treating Stomatitis in Patients With ER- or PR-Positive Metastatic or Locally Recurrent Breast Cancer That Cannot be Removed by Surgery Receiving Everolimus

PRIMARY OBJECTIVES:

I. Evaluate whether use of prophylactic MuGard (mucoadhesive oral wound rinse) in
participants being treated with everolimus will reduce the rate of stomatitis.

SECONDARY OBJECTIVES:

I. Compare symptoms from mouth sores in patients receiving MuGard compared with those
receiving best supportive care.

II. Evaluate the rate of everolimus dose adjustment or therapy discontinuation as a result of
stomatitis in participants treated with MuGard prophylaxis versus best supportive care.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive mucoadhesive oral wound rinse orally (PO) as a gentle swish for 30-60
seconds 3-6 times daily beginning on day 1 of everolimus therapy and continuing for up to 6
months in the absence of unacceptable toxicity.

ARM II: Patients receive no intervention.

After completion of study treatment, patients are followed up within 7 days.

Inclusion Criteria:

- Metastatic or locally recurrent unresectable breast cancer

- Histological or cytological confirmed ER and/or PR positivity

- Progression through at least one prior line of endocrine therapy

- Participant is scheduled to initiate treatment with everolimus combined with
exemestane or another form of endocrine therapy

- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

- Platelets >= 100 x 10^9/L

- Hemoglobin (Hgb) ≥>= 8.0 g/dL

- International normalized ratio (INR) =< 2

- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X
upper limit of normal (ULN) (or =< 5 X ULN if hepatic metastases are present)

Exclusion Criteria:

- Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer by local
laboratory testing (immunohistochemistry [IHC] 3+ staining or fluorescent in situ
hybridization [FISH] positive)

- Baseline presence of oral ulcers

- Prior treatment with everolimus or another mammalian target of rapamycin (mTOR)
inhibitor (temsirolimus)

- Patients on warfarin (patients on injectable blood thinners, such as Lovenox, are able
to continue those)

- Patients currently receiving chemotherapy or who have received chemotherapy less than
4 weeks of the start of everolimus (including chemotherapy, radiation therapy,
antibody based therapy, etc.)

- Known impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of oral everolimus

- Uncontrolled diabetes mellitus as defined by hemoglobin A1c (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

- 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, and chronic hepatitis (i.e. quantifiable
hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B
virus surface antigen [HbsAg], quantifiable hepatitis C virus [HCV]-ribonucleic
acid [RNA])

- Known severely impaired lung function (spirometry and diffusing capacity of the
lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation
88% or less at rest on room air)

- Active, bleeding diathesis

- Chronic treatment with corticosteroids or other immunosuppressive agents; topical or
inhaled corticosteroids are allowed

- Known history of human immunodeficiency virus (HIV) seropositivity

- 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, Bacillus
Calmette-Guérin (BCG), yellow fever, varicella and TY21a typhoid vaccines

- 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

- Patients who are currently part of or have participated in any clinical investigation
with an investigational drug within 1 month prior to dosing

- Pregnant or nursing (lactating) women

- Women of child-bearing potential (WOCBP), defined as all women physiologically capable
of becoming pregnant, must use highly effective methods of contraception during the
study and 8 weeks after; highly effective contraception methods include combination of
any two of the following:

- Use of oral, injected or implanted hormonal methods of contraception or

- Placement of an intrauterine device (IUD) or intrauterine system (IUS)

- Barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository

- Total abstinence or

- Male/female sterilization Women are considered post-menopausal and not of
child-bearing potential if they have had 12 months of natural (spontaneous)
amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of
vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks prior to randomization; in the
case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment is she considered not of
child-bearing potential