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

NCT ID: NCT02069093

Last Updated: 2017-02-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2016-03-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Dexamethasone based mouthwash

Intervention Type: DRUG

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

Everolimus

Intervention Type: DRUG

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

Exemestane

Intervention Type: DRUG

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

Interventions

Dexamethasone based mouthwash

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

Intervention Type: DRUG

Everolimus

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

Intervention Type: DRUG

Exemestane

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

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Highlands Oncology Group Highlands Oncology Group (22)

Fayetteville, Arkansas, 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

University of California at Los Angeles UCLA and TRIO Network

Los Angeles, California, United States

University of California Irvine UC Irvine Medical Center

Orange, California, United States

University of California San Francisco UCSF Medical Center

San Francisco, California, United States

California Pacific Medical Center SC

San Francisco, California, United States

University of Connecticut Health Center

Farmington, Connecticut, United States

Southeastern Regional Medical Center

Newnan, Georgia, United States

OnCare Hawaii

‘Aiea, Hawaii, United States

North Shore University Health System NorthShore University

Evanston, Illinois, United States

Oncology Specialists, SC Onc Specialists

Park Ridge, Illinois, United States

University of Maryland School of Medicine University of Maryland

Baltimore, Maryland, United States

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

Rockville, Maryland, United States

Karmanos Cancer Institute Karmanos Cancer Institute (2)

Detroit, Michigan, United States

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

Kansas City, Missouri, United States

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

M. Francisco Gonzalez, MD.PA Hematology Oncology Center

Columbia, South Carolina, 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

Delta Oncology Associates Delta Hematology/Oncology

Portsmouth, Virginia, United States

Northwest Medical Specialties Northwest Medical - Puyallup

Tacoma, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32043762 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28314691 (View on PubMed)

Other Identifiers

CRAD001JUS226

Identifier Type: -

Identifier Source: org_study_id