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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02069093
Recruitment Status : Completed
First Posted : February 21, 2014
Results First Posted : February 13, 2017
Last Update Posted : February 13, 2017
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief 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

Condition or disease Intervention/treatment Phase
Advanced Breast Cancer Drug: Dexamethasone based mouthwash Drug: Everolimus Drug: Exemestane Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 92 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : May 2014
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Dexamethasone based mouthwash
Participants swished and spat 10mL of 0.5mg/5mL dexamethasone steroid mouthwash (investigational treatment) 4 times daily (qid) orally for 2 minutes each for 8 weeks. Participants remained without food or drink (NPO) for one hour after administration of the mouthwash. Also, participants received everolimus 10 mg and exemstane 25 mg (study treatments) according to local regulations.
Drug: Dexamethasone based mouthwash
Dexamethasone steroid-based oral solution, comprised of 0.5 milligrams per 5mL of alcohol-free dexamethasone.

Drug: Everolimus
Commercially available everolimus 10 mg was prescribed to participants by the Investigator according to local regulations.

Drug: Exemestane
Commercially available exemestane 25 mg was prescribed to participants by the Investigator according to local regulations.

Primary Outcome Measures :
  1. Number of Participants With Stomatitis Grade ≥ 2 [ Time Frame: 56 days ]
    The incidence of grade ≥ 2 stomatitis was reported. Grade 1 = minimal symptoms, normal diet; grade 2 = symptomatic, but able to swallow a modified diet; grade 3 = symptomatic and unable to aliment or hydrate orally; and grade 4 = symptoms associated with life-threatening consequences.

Secondary Outcome Measures :
  1. Time to Resolution of Stomatitis From Grade 2 or Greater to Grade 1 or Less [ Time Frame: 56 days ]
    The number of days to achieve resolution of stomatitis from grade 2 or greater to grade 1 or less was assessed. Grade 1 = minimal symptoms, normal diet; grade 2 = symptomatic, but able to swallow a modified diet; grade 3 = symptomatic and unable to aliment or hydrate orally; and grade 4 = symptoms associated with life-threatening consequences.

  2. Median Number of Mouthwashes Per Day [ Time Frame: 56 days ]
    The median number of mouthwashes per day was assessed.

  3. Number of Participants With All Grades of Stomatitis [ Time Frame: 56 days ]
    The number of participants with all grades of stomatitis was defined as the number of participants who had stomatitis grade 1 or higher. Grade 1 = minimal symptoms, normal diet; grade 2 = symptomatic, but able to swallow a modified diet; grade 3 = symptomatic and unable to aliment or hydrate orally; and grade 4 = symptoms associated with life-threatening consequences.

  4. Dose Intensity of Everolimus and Exemestane [ Time Frame: 56 days ]
    The dose intensity was calculated as the cumulative dose of everolimus or exemestane divided by the length of time on treatment during the first 56 days of treatment.

  5. Blood Concentration of Everolimus and Exemestane [ Time Frame: 28 days (pre-dose) ]
    Blood samples were collected and analyzed.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): 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
University of California San Francisco UCSF Medical Center
San Francisco, California, United States, 94101
California Pacific Medical Center SC
San Francisco, California, United States, 94115
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
Oncology Consultants Oncology Consultants, P.A.
Houston, Texas, United States, 77024
University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(2)
Houston, Texas, United States, 77030-4009
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

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals Identifier: NCT02069093     History of Changes
Other Study ID Numbers: CRAD001JUS226
First Posted: February 21, 2014    Key Record Dates
Results First Posted: February 13, 2017
Last Update Posted: February 13, 2017
Last Verified: December 2016

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Mouth Diseases
Stomatognathic Diseases
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors