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

NCT02069093 | Completed Phase 2 Results

• 1 other identifier: CRAD001JUS226
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 23

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

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Stomatitis Grade ≥ 2

  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.

  56 days

Secondary Outcomes (5)

• Time to Resolution of Stomatitis From Grade 2 or Greater to Grade 1 or Less

  56 days

• Median Number of Mouthwashes Per Day

  56 days

• Number of Participants With All Grades of Stomatitis

  56 days

• Dose Intensity of Everolimus and Exemestane

  56 days

• Blood Concentration of Everolimus and Exemestane

  28 days (pre-dose)

Study Arms (1)

Dexamethasone based mouthwash

EXPERIMENTAL

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; Drug: Everolimus; Drug: Exemestane

Interventions

Dexamethasone based mouthwash DRUG

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

Dexamethasone based mouthwash

Everolimus DRUG

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

Dexamethasone based mouthwash

Exemestane DRUG

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

Dexamethasone based mouthwash

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult women \> 18 years of age with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy
• Histological or cytological confirmation of hormone-receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer
• 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
• 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
• Patient must start everolimus 10mg plus exemestane 25mg treatment on Cycle 1 Day 1 of trial
• ECOG Performance status ≤ 2
• Adequate renal function: serum creatinine ≤ 1.5x ULN;
• 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
• Signed informed consent obtained prior to any screening procedure

You may not qualify if:

• Patients currently receiving anticancer therapies (except biphosphonate, denosumab);
• Patients who currently have stomatitis/oral mucositis/mouth ulcers;
• Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus);
• Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus;
• 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;
• 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;
• Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled corticosteroids are allowed;
• Known history of HIV seropositivity;
• 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;
• 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;

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (23)

Highlands Oncology Group Highlands Oncology Group (22)

Fayetteville, Arkansas, 72703, United States

Location

Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C

Anaheim, California, 92807, United States

Location

Los Angeles Hematology/Oncology Medical Group

Los Angeles, California, 90017, United States

Location

University of California at Los Angeles UCLA and TRIO Network

Los Angeles, California, 90095-6956, United States

Location

University of California Irvine UC Irvine Medical Center

Orange, California, 92868, United States

Location

University of California San Francisco UCSF Medical Center

San Francisco, California, 94101, United States

Location

California Pacific Medical Center SC

San Francisco, California, 94115, United States

Location

University of Connecticut Health Center

Farmington, Connecticut, 06030-3940, United States

Location

Southeastern Regional Medical Center

Newnan, Georgia, 30265, United States

Location

OnCare Hawaii

‘Aiea, Hawaii, 96701, United States

Location

North Shore University Health System NorthShore University

Evanston, Illinois, 60201, United States

Location

Oncology Specialists, SC Onc Specialists

Park Ridge, Illinois, 60068-0736, United States

Location

University of Maryland School of Medicine University of Maryland

Baltimore, Maryland, 21201-1559, United States

Location

Kaiser Permanente - Mid Atlantic Permanete Research Institut Kaiser Permanente Mid-Atlantic

Rockville, Maryland, 20850, United States

Location

Karmanos Cancer Institute Karmanos Cancer Institute (2)

Detroit, Michigan, 48201, United States

Location

Saint Luke's Hospital/Marion Bloch Neuroscience Institute Cancer Institute

Kansas City, Missouri, 64111, United States

Location

Regional Cancer Care Associates Cancer and Hematologic Disease

Cherry Hill, New Jersey, 08003, United States

Location

Hematology Oncology Associates of Northern New Jersey PA DeptofHem-OncofNorthern NJ (2)

Morristown, New Jersey, 07962, United States

Location

M. Francisco Gonzalez, MD.PA Hematology Oncology Center

Columbia, South Carolina, 29203, United States

Location

Oncology Consultants Oncology Consultants, P.A.

Houston, Texas, 77024, United States

Location

University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(2)

Houston, Texas, 77030-4009, United States

Location

Delta Oncology Associates Delta Hematology/Oncology

Portsmouth, Virginia, 23704, United States

Location

Northwest Medical Specialties Northwest Medical - Puyallup

Tacoma, Washington, 98405, United States

Location

Related Publications (2)

• Niikura N, Nakatukasa K, Amemiya T, Watanabe KI, Hata H, Kikawa Y, Taniike N, Yamanaka T, Mitsunaga S, Nakagami K, Adachi M, Kondo N, Shibuya Y, Hayashi N, Naito M, Kashiwabara K, Yamashita T, Umeda M, Mukai H, Ota Y. Oral Care Evaluation to Prevent Oral Mucositis in Estrogen Receptor-Positive Metastatic Breast Cancer Patients Treated with Everolimus (Oral Care-BC): A Randomized Controlled Phase III Trial. Oncologist. 2020 Feb;25(2):e223-e230. doi: 10.1634/theoncologist.2019-0382. Epub 2019 Oct 8.

  PMID: 32043762 DERIVED

• Rugo HS, Seneviratne L, Beck JT, Glaspy JA, Peguero JA, Pluard TJ, Dhillon N, Hwang LC, Nangia C, Mayer IA, Meiller TF, Chambers MS, Sweetman RW, Sabo JR, Litton JK. Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial. Lancet Oncol. 2017 May;18(5):654-662. doi: 10.1016/S1470-2045(17)30109-2. Epub 2017 Mar 15.

  PMID: 28314691 DERIVED

MeSH Terms

Interventions

Everolimus; exemestane

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2014
• First Posted: February 21, 2014
• Study Start: May 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: February 13, 2017
• Results First Posted: February 13, 2017

Record last verified: 2016-12

Locations

US (23)