Miracle Mouthwash Plus Hydrocortisone vs Prednisolone Mouth Rinse for Mouth Sores Caused by Everolimus

Overview

This is a randomized Phase 2 study to evaluate two different steroid-based mouth rinses (Miracle Mouth Wash plus hydrocortisone versus prednisolone oral rinse) for the prevention or treatment of everolimus-associated stomatitis (mouth sores) in postmenopausal patients undergoing treatment with an aromatase inhibitor plus everolimus. An exploratory analysis will also evaluate patient response to next anti-cancer therapy of physician's choice following discontinuation of therapy with an aromatase inhibitor plus everolimus.

Stomatitis, or inflammation of the mucous membranes lining the mouth and throat, is a common side affect associated with chemotherapy and radiation therapy. In addition, stomatitis has been reported in approximately 44% - 64% of patients treated with everolimus (Afinitor PI). However, mTOR (mammalian target of rapamycin) inhibitor-induced stomatitis (mIAS) is a different clinical entity, manifesting more frequently as discrete aphthous-like lesions rather than diffuse inflammation. Oral lesions are typically well demarcated, single or multiple ovoid-shaped ulcerations, with a grayish-white pseudomembrane. In the BOLERO-2 trial, 56% of patients with MBC (metastatic breast cancer) treated with exemestane plus everolimus developed stomatitis, with 37% developing grade 2/3 stomatitis. These rates are consistent with the rates reported with everolimus therapy in patients with other types of cancers (Afinitor PI). Although this adverse event is reversible, approximately one-fourth of the patients treated with everolimus in the BOLERO-2 trial required dose interruptions or dose reductions, and this may impact the benefit from therapy. Despite the frequency of stomatitis associated with mTOR inhibitor therapy, strategies to prevent and/or ameliorate this painful side effect are not well defined or documented. Expert guidelines on the management of mIAS have been developed, but these guidelines are based on retrospective observational and/or anecdotal evidence, and prospective data on the efficacy of mIAS prevention and management strategies are needed. There is some evidence to suggest steroid therapy may be helpful in the management of mIAS. Steroid-containing ointments or mouth rises have also been shown to alleviate symptoms in patients with non-chemotherapy associated apthous oral ulcers. Reports on the effectiveness of non-steroid mouthwash formulations have been mixed, but agents that induce a topical anesthetic effect, may help to reduce discomfort and pain. Thus, the present study has been designed to investigate the effectiveness of two oral rinses (miracle mouth wash \[MMW\] plus hydrocortisone, vs prednisolone) to prevent or reduce the severity of stomatitis in patients with MBC undergoing treatment with an aromatase inhibitor plus everolimus (AIE). In addition, because very little is known about the impact of everolimus therapy on response to later lines of treatment for MBC, and preclinical data suggest mTOR inhibition may resensitize cells to endocrine therapy, this study will also assess tumor response to next anti-cancer therapy of physician's choice, including duration of response and sites of progression. All patients will receive everolimus 10 mg PO QD (by mouth, every day) plus standard dose AI (physician choice of Letrozole, Exemestane, or Anastrozole). Patients will be randomized 1:1 to 12 weeks of treatment with either: * Arm 1: MMW plus hydrocortisone * Arm 2: Prednisolone oral solution (15mg/5ml) Treatment with the oral rinse will start on Day 1 of everolimus therapy, and will be self-administered. Patients will be instructed to swish and expectorate (cough or spit out) 10ml of the assigned mouth rinse 4 times per day. Patients may also gargle 4 times per day with the assigned rinse for any symptoms of pharyngitis. Patients will also be instructed to fill out the Oral Stomatitis Daily Questionnaire (OSDQ) at home every day. The incidence of stomatitis, as well as other adverse events, dose reductions/interruptions, and everolimus discontinuation due to toxicity, will be monitored for the first 12 weeks of treatment. After the end of the initial 12 week randomized portion of the study, patients will continue to be followed every 2 months (for up to 1 year following discontinuation of everolimus for progression or intolerable toxicity or progression on subsequent anti-cancer therapy, whichever occurs first) to determine when AIE treatment is discontinued and reason for discontinuation (toxicity, progression), sites of disease progression, response to next anti-cancer therapy of physician's choice (by physician assessment) and duration of response, and sites of disease progression to next anti-cancer therapy following progression on AIE.