Clinical Trials /

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

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: CRAD001JUS226
  • NCT ID: NCT02069093

Conditions

  • Advanced Breast Cancer

Interventions

DrugSynonymsArms
Dexamethasone based mouthwashDexamethasone based mouthwash
EverolimusDexamethasone based mouthwash
ExemestaneDexamethasone based mouthwash

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Dexamethasone based mouthwashExperimentalParticipants 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
  • Exemestane

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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With Stomatitis Grade ≥ 2
Time Frame:56 days
Safety Issue:
Description: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

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Novartis Pharmaceuticals

Last Updated

December 20, 2016