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

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: February 20, 2014
Last updated: May 5, 2016
Last verified: May 2016
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

Condition Intervention Phase
Advanced Breast Cancer
Drug: Dexamethasone based mouth
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase II, Single Arm Study of the Use of Steroid-based Mouthwash to Prevent Stomatitis in Postmenopausal Women With Advanced or Metastatic Hormone Receptor Positive Breast Cancer Being Treated With Everolimus Plus Exemestane

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence of Grade ≥ 2 stomatitis at 2 months [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]
    Report the incidence of Grade ≥ 2 stomatitis at 2 months, in patients using prophylactic steroid mouthwash alcohol-free dexamethasone 0.5mg/5ml and compare to BOLERO-2 historical controls, in postmenopausal women with advanced or metastatic hormone receptor positive breast cancer.

Secondary Outcome Measures:
  • Average time to resolution [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]
    Average number of times per day mouthwash regimen performed at 2-months (56 days). Dose intensity of everolimus and exemestane at 2-months (56 days). Incidence of all grades stomatitis at 2-months (56 days). Time to resolution (total # days) from diagnosis of stomatitis (Gr>2) to resolution (Gr≤ 1).

Enrollment: 92
Study Start Date: May 2014
Study Completion Date: March 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dexamethasone based mouthwash
Dexamethasone based mouthwash in postmenopausal women with advanced or metastatic hormone receptor positive breast cancer being treated with everolimus plus exemestane
Drug: Dexamethasone based mouth
Dexamethasone steroid-based oral solution, comprised of 0.5 milligrams per 5mL of alcohol-free dexamethasone.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02069093

  Hide Study Locations
United States, Arkansas
Highlands Oncology Group Highlands Oncology Group (22)
Fayetteville, Arkansas, United States, 72703
United States, California
Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C
Anaheim, California, United States, 92807
Los Angeles Hematology/Oncology Medical Group
Los Angeles, California, United States, 90017
University of California at Los Angeles UCLA and TRIO Network
Los Angeles, California, United States, 90095-6956
University of California Irvine UC Irvine Medical Center
Orange, California, United States, 92868
California Pacific Medical Center SC
San Francisco, California, United States, 94115
University of California San Francisco UCSF Medical Center
San Francisco, California, United States, 94101
United States, Connecticut
University of Connecticut Health Center
Farmington, Connecticut, United States, 06030-3940
United States, Georgia
Southeastern Regional Medical Center
Newnan, Georgia, United States, 30265
United States, Hawaii
OnCare Hawaii
Aiea, Hawaii, United States, 96701
United States, Illinois
North Shore University Health System NorthShore University
Evanston, Illinois, United States, 60201
Oncology Specialists, SC Onc Specialists
Park Ridge, Illinois, United States, 60068-0736
United States, Maryland
University of Maryland School of Medicine University of Maryland
Baltimore, Maryland, United States, 21201-1559
Kaiser Permanente - Mid Atlantic Permanete Research Institut Kaiser Permanente Mid-Atlantic
Rockville, Maryland, United States, 20850
United States, Michigan
Karmanos Cancer Institute Karmanos Cancer Institute (2)
Detroit, Michigan, United States, 48201
United States, Missouri
Saint Luke's Hospital/Marion Bloch Neuroscience Institute Cancer Institute
Kansas City, Missouri, United States, 64111
United States, New Jersey
Regional Cancer Care Associates Cancer and Hematologic Disease
Cherry Hill, New Jersey, United States, 08003
Hematology Oncology Associates of Northern New Jersey PA DeptofHem-OncofNorthern NJ (2)
Morristown, New Jersey, United States, 07962
United States, South Carolina
M. Francisco Gonzalez, MD.PA Hematology Oncology Center
Columbia, South Carolina, United States, 29203
United States, Texas
University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(2)
Houston, Texas, United States, 77030-4009
Oncology Consultants Oncology Consultants, P.A.
Houston, Texas, United States, 77024
United States, Virginia
Delta Oncology Associates Delta Hematology/Oncology
Portsmouth, Virginia, United States, 23704
United States, Washington
Northwest Medical Specialties Northwest Medical - Puyallup
Tacoma, Washington, United States, 98405
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis ( Novartis Pharmaceuticals ) Identifier: NCT02069093     History of Changes
Other Study ID Numbers: CRAD001JUS226 
Study First Received: February 20, 2014
Last Updated: May 5, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Mouth Diseases
Neoplasms by Site
Skin Diseases
Stomatognathic Diseases
BB 1101
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Enzyme Inhibitors
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Physiological Effects of Drugs
Protease Inhibitors processed this record on May 23, 2016