Clinical trial NCT02069093: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Breast Cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-02-21
Enrollment: 92
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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


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).

Primary outcomes:
measure: Number of Participants With Stomatitis Grade ≥ 2
timeFrame: 56 days
Secondary outcomes:
measure: Time to Resolution of Stomatitis From Grade 2 or Greater to Grade 1 or Less
timeFrame: 56 days
measure: Median Number of Mouthwashes Per Day
timeFrame: 56 days
measure: Number of Participants With All Grades of Stomatitis
timeFrame: 56 days
measure: Dose Intensity of Everolimus and Exemestane
timeFrame: 56 days
measure: Blood Concentration of Everolimus and Exemestane
timeFrame: 28 days (pre-dose)
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group Highlands Oncology Group (22)
state: Arkansas
city: Anaheim
country: United States
facility: Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C
state: California
city: Los Angeles
country: United States
facility: Los Angeles Hematology/Oncology Medical Group
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles UCLA and TRIO Network
state: California
city: Orange
country: United States
facility: University of California Irvine UC Irvine Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco UCSF Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center SC
state: California
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Newnan
country: United States
facility: Southeastern Regional Medical Center
state: Georgia
city: Aiea
country: United States
facility: OnCare Hawaii
state: Hawaii
city: Evanston
country: United States
facility: North Shore University Health System NorthShore University
state: Illinois
city: Park Ridge
country: United States
facility: Oncology Specialists, SC Onc Specialists
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland School of Medicine University of Maryland
state: Maryland
city: Rockville
country: United States
facility: Kaiser Permanente - Mid Atlantic Permanete Research Institut Kaiser Permanente Mid-Atlantic
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute Karmanos Cancer Institute (2)
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Hospital/Marion Bloch Neuroscience Institute Cancer Institute
state: Missouri
city: Cherry Hill
country: United States
facility: Regional Cancer Care Associates Cancer and Hematologic Disease
state: New Jersey
city: Morristown
country: United States
facility: Hematology Oncology Associates of Northern New Jersey PA DeptofHem-OncofNorthern NJ (2)
state: New Jersey
city: Columbia
country: United States
facility: M. Francisco Gonzalez, MD.PA Hematology Oncology Center
state: South Carolina
city: Houston
country: United States
facility: Oncology Consultants Oncology Consultants, P.A.
state: Texas
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(2)
state: Texas
city: Portsmouth
country: United States
facility: Delta Oncology Associates Delta Hematology/Oncology
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties Northwest Medical - Puyallup
state: Washington
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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. 2019 Oct 8:theoncologist.2019-0382. doi: 10.1634/theoncologist.2019-0382. Online ahead of print.
citation: 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.