Clinical trial NCT02322853 (phase 2, status: terminated)
Conditions: postmenopausal, metastatic breast cancer
ICD codes: N95.0, N95.2, C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: tamoxifen, ralimetinib (ly2228820 dimesylate)
SMILES: OC1=CC=C(C=C1)C1=C(C(=O)C2=CC=C(OCCN3CCCCC3)C=C2)C2=C(S1)C=C(O)C=C2, CC(C)(C)CN1C(N)=NC2=CC=C(N=C12)C1=C(NC(=N1)C(C)(C)C)C1=CC=C(F)C=C1
Reason stopped: 
    lack of recruitment
  
Eligibility criteria:

        Inclusion Criteria:

          -  Women with histologically confirmed breast cancer

          -  18 < age < 80 years old

          -  Menopausal status Women are considered post-menopausal and not of child bearing
             potential if they have had

               -  12 months of spontaneous amenorrhea with an appropriate clinical profile (e.g.,
                  age appropriate, history of vasomotor symptoms) or

               -  6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and
                  estradiol < 20 pg/mL or

               -  surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks
                  ago. In the case of oophorectomy alone, only when the reproductive status of the
                  woman has been confirmed by follow up hormone level assessment is she considered
                  not of child bearing potential

          -  ER-positive status by local laboratory testing (>10% by IHC) and HER2-negative status
             (IHC 0 or 1+ or 2+ and FISH negative) on the last biopsy or surgical specimen
             available.

          -  Disease progression defined as inoperable locally advanced or metastatic breast cancer
             (MBC) excluding aggressive visceral disease requiring other approaches, such as
             chemotherapy

          -  Disease refractory to aromatase inhibitors (AI) defined as:

               -  recurrence while on, or within 12 months of end of adjuvant treatment with
                  aromatase inhibitor, or

               -  progression while on, or within 3 months of end of AI for locally advanced or MBC

          -  Patients who have received fulvestrant are eligible

          -  Maximum 2 previous lines of chemotherapy for MBC

          -  Performance Status (PS) ≤ 2

          -  Patient able to swallow and retain oral medication

          -  Measurable or evaluable lesions as per RECIST 1.1

               -  Measurable disease (≥ 20 mm by conventional techniques or ≥ 10 mm by spiral
                  computed tomography scan) or

               -  Non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of
                  measurable disease.

               -  Patients with only pleural effusion and/or ascites are not eligible.

          -  Adequate bone marrow and organ function as defined by the following laboratory values:

               -  Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L

               -  Platelets (plt) ≥ 100 x 109/L

               -  Hemoglobin (Hgb) ≥ 9 g/dl

               -  INR ≤ 1.5 without any anticoagulation treatment

               -  Serum creatinine ≤ 1.5 x ULN

               -  Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) within normal
                  range (or < 3.0 x ULN if liver metastases are present)

               -  Total serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are
                  present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range
                  in patients with well documented Gilbert's Syndrome, which is defined as presence
                  of several episodes of unconjugated hyperbilirubinemia with normal results from
                  CBC count (including normal reticulocyte count and blood smear), normal liver
                  function test results, and absence of other contributing disease processes at the
                  time of diagnosis

          -  Patient has signed informed consents obtained before any trial related activities and
             according to local guidelines

        Exclusion Criteria:

          -  • Previous treatment with p38 MAPK inhibitors or Tamoxifen in metastatic setting
             (adjuvant treatment by tamoxifen is allowed)

               -  More than 2 lines of chemotherapy for locally advanced and/or metastatic breast
                  cancer

               -  Brain metastasis

               -  Other malignancy (with the exception of adequately treated, basal or squamous
                  cell carcinoma, non-melanomatous skin cancer or curatively resected cervical
                  cancer).

               -  Clinically significant (i.e. active) cardiovascular disease: cerebro-vascular
                  accident/stroke or myocardial infarction within 6 months prior to first study
                  medication; unstable angina; CHF of New York Heart Association (NYHA) Grade II or
                  higher; or serious cardiac arrhythmia requiring medication.

               -  Have had a major bowel resection that would alter oral drug absorption.

               -  Have a diagnosis of inflammatory bowel disease (Crohn's disease or ulcerative
                  colitis).

               -  Are receiving concurrent administration of immunosuppressive therapy

               -  Concurrent participation in any therapeutic clinical trial

               -  Assessed by the investigator to be unable or unwilling to comply with the
                  requirements of the protocol