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

Advanced Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02069093
• Other study ID #: CRAD001JUS226
• Status: Completed
• Phase: Phase 2
• First received: February 20, 2014
• Last updated: May 5, 2016
• Start date: May 2014
• Est. completion date: March 2016

Study information

• Verified date: May 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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).

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms
• Stomatitis

Intervention

Drug:
• Dexamethasone based mouth
Dexamethasone steroid-based oral solution, comprised of 0.5 milligrams per 5mL of alcohol-free dexamethasone.

Locations

Country	Name	City	State
United States	OnCare Hawaii	Aiea	Hawaii
United States	Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C	Anaheim	California
United States	University of Maryland School of Medicine University of Maryland	Baltimore	Maryland
United States	Regional Cancer Care Associates Cancer and Hematologic Disease	Cherry Hill	New Jersey
United States	M. Francisco Gonzalez, MD.PA Hematology Oncology Center	Columbia	South Carolina
United States	Karmanos Cancer Institute Karmanos Cancer Institute (2)	Detroit	Michigan
United States	North Shore University Health System NorthShore University	Evanston	Illinois
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Highlands Oncology Group Highlands Oncology Group (22)	Fayetteville	Arkansas
United States	Oncology Consultants Oncology Consultants, P.A.	Houston	Texas
United States	University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(2)	Houston	Texas
United States	Saint Luke's Hospital/Marion Bloch Neuroscience Institute Cancer Institute	Kansas City	Missouri
United States	Los Angeles Hematology/Oncology Medical Group	Los Angeles	California
United States	University of California at Los Angeles UCLA and TRIO Network	Los Angeles	California
United States	Hematology Oncology Associates of Northern New Jersey PA DeptofHem-OncofNorthern NJ (2)	Morristown	New Jersey
United States	Southeastern Regional Medical Center	Newnan	Georgia
United States	University of California Irvine UC Irvine Medical Center	Orange	California
United States	Oncology Specialists, SC Onc Specialists	Park Ridge	Illinois
United States	Delta Oncology Associates Delta Hematology/Oncology	Portsmouth	Virginia
United States	Kaiser Permanente - Mid Atlantic Permanete Research Institut Kaiser Permanente Mid-Atlantic	Rockville	Maryland
United States	California Pacific Medical Center SC	San Francisco	California
United States	University of California San Francisco UCSF Medical Center	San Francisco	California
United States	Northwest Medical Specialties Northwest Medical - Puyallup	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Grade = 2 stomatitis at 2 months	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.	56 days	Yes
Secondary	Average time to resolution	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).	56 days	Yes