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

Phase 2

Completed

• Conditions: Advanced Breast Cancer
• Interventions: Drug: Dexamethasone based mouthwash; Drug: Everolimus; Drug: Exemestane

• Registration Number: NCT02069093
• Lead Sponsor: 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-02-20
• Study First Submitted QC: 2014-02-20
• Study First Posted: 2014-02-21
• Study Start: 2014-05
• Primary Completion: 2016-03
• Study Completion: 2016-03
• Results First Submitted: 2016-10-19
• Status Verified: 2016-12
• Results First Submitted QC: 2016-12-20
• Last Update Submitted: 2016-12-20
• Results First Posted: 2017-02-13
• Last Update Posted: 2017-02-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 92

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).

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dexamethasone based mouthwash	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.
Dexamethasone based mouthwash	Exemestane	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.
Dexamethasone based mouthwash	Everolimus	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Stomatitis Grade ≥ 2	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

Name	Time	Method
Time to Resolution of Stomatitis From Grade 2 or Greater to Grade 1 or Less	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.
Median Number of Mouthwashes Per Day	56 days	The median number of mouthwashes per day was assessed.
Number of Participants With All Grades of Stomatitis	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.
Dose Intensity of Everolimus and Exemestane	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.
Blood Concentration of Everolimus and Exemestane	28 days (pre-dose)	Blood samples were collected and analyzed.

Trial Locations

Locations (23)

Regional Cancer Care Associates Cancer and Hematologic Disease; 🇺🇸 Cherry Hill, New Jersey, United States

Hematology Oncology Associates of Northern New Jersey PA DeptofHem-OncofNorthern NJ (2); 🇺🇸 Morristown, New Jersey, United States

Highlands Oncology Group Highlands Oncology Group (22); 🇺🇸 Fayetteville, Arkansas, United States

OnCare Hawaii; 🇺🇸 Aiea, Hawaii, United States

Kaiser Permanente - Mid Atlantic Permanete Research Institut Kaiser Permanente Mid-Atlantic; 🇺🇸 Rockville, Maryland, United States

Oncology Specialists, SC Onc Specialists; 🇺🇸 Park Ridge, Illinois, United States

California Pacific Medical Center SC; 🇺🇸 San Francisco, California, United States

University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(2); 🇺🇸 Houston, Texas, United States

Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C; 🇺🇸 Anaheim, California, United States

Los Angeles Hematology/Oncology Medical Group; 🇺🇸 Los Angeles, California, United States

Delta Oncology Associates Delta Hematology/Oncology; 🇺🇸 Portsmouth, Virginia, United States

University of California at Los Angeles UCLA and TRIO Network; 🇺🇸 Los Angeles, California, United States

University of Maryland School of Medicine University of Maryland; 🇺🇸 Baltimore, Maryland, United States

University of Connecticut Health Center; 🇺🇸 Farmington, Connecticut, United States

North Shore University Health System NorthShore University; 🇺🇸 Evanston, Illinois, United States

Karmanos Cancer Institute Karmanos Cancer Institute (2); 🇺🇸 Detroit, Michigan, United States

M. Francisco Gonzalez, MD.PA Hematology Oncology Center; 🇺🇸 Columbia, South Carolina, United States

Northwest Medical Specialties Northwest Medical - Puyallup; 🇺🇸 Tacoma, Washington, United States

University of California San Francisco UCSF Medical Center; 🇺🇸 San Francisco, California, United States

Southeastern Regional Medical Center; 🇺🇸 Newnan, Georgia, United States

Oncology Consultants Oncology Consultants, P.A.; 🇺🇸 Houston, Texas, United States

Saint Luke's Hospital/Marion Bloch Neuroscience Institute Cancer Institute; 🇺🇸 Kansas City, Missouri, United States

University of California Irvine UC Irvine Medical Center; 🇺🇸 Orange, California, United States