Letrozole and Imatinib Mesylate in Treating Postmenopausal Participants With Estrogen or Progesterone Positive Metastatic Breast Cancer
Condition: Anatomic Stage IV Breast Cancer AJCC v8; Estrogen Receptor Positive; KIT Positive; PDGFR Positive; Postmenopausal; Progesterone Receptor Positive; Prognostic Stage IV Breast Cancer AJCC v8
MeSH terms: Breast Neoplasms
Intervention: Imatinib Mesylate; Letrozole
Intervention description: Given PO; Given PO
Intervention MeSH terms: Letrozole; Imatinib Mesylate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: Female
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and how well letrozole and imatinib mesylate
      work in treating postmenopausal participants with estrogen or progesterone positive breast
      cancer that has spread to other places in the body. Letrozole is an antihormonal drug used in
      the standard treatment of hormonal sensitive breast cancer. Imatinib mesylate is a drug that
      binds to certain proteins on the tumor cells and prevents them from further growth. Imatinib
      mesylate is thought to prevent the potential resistance to letrozole, which may make the
      letrozole more effective. Giving letrozole and imatinib mesylate may work better in treating
      participants with breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Postmenopausal women able to comply with the protocol requirements with metastatic
             breast cancer, whose tumors are estrogen (ER) and/or progesterone (PgR) positive,
             defined by core biopsy immunohistochemistry with greater than 10% positive malignant
             epithelial cells

          -  Patients must have documented expression of either PDGFR or CD117 (c-kit) by
             immunohistochemistry

          -  Patients may have received tamoxifen in the adjuvant/neoadjuvant or setting. Patients
             may have previously received chemotherapy in the adjuvant/ neoadjuvant setting, though
             this is not required. Prior chemotherapy for metastatic breast cancer is allowed.
             Concomitant bisphosphonates are allowed for patients with bone metastases and who have
             another site of measurable disease

          -  Post menopausal status defined by one of the following: no spontaneous menses for at
             least 1 year, in women greater than or equal to 55 years spontaneous menses within the
             past 1 year in women greater than or equal to 55 years with postmenopausal
             gonadotrophin levels (luteinizing hormone [LH] and follicle stimulating hormone [FSH]
             levels greater than 40 IU/L ) or postmenopausal estradiol levels (less than 5 mg/dl)
             or according to the definition of "postmenopausal range" for the laboratory involved
             bilateral oophorectomy

          -  Performance status, Eastern Cooperative Oncology Group (ECOG) greater than or equal to
             2

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as
             greater than or equal to 10 mm with conventional techniques. Bone disease only will
             not be accepted as measurable disease. Pleural or peritoneal effusions will not be
             accepted as measurable disease

          -  Absolute neutrophil count (ANC) = 1.5 x 10 to the 9th power/L

          -  Platelets greater than or equal to 100.0 x 10 to the 9th power/L

          -  Hemoglobin greater than 10.0 g/dL

          -  Creatinine less than 1.5 mg/dl

          -  Total (T.) bilirubin less than 1.5 x normal

          -  Aspartate aminotransferase (AST) less than 2.5 x normal

          -  A life expectancy of at least 6 months

          -  Localized radiotherapy, which does not influence the signal of evaluable lesion, is
             allowed prior to the initiation of imatinib mesylate. Patients must have recovered
             from the myelosuppressive effects of previous radiotherapy (at least 2-4 weeks)

          -  Ability to understand and the willingness to sign a written informed consent

        Exclusion Criteria:

          -  Prior treatment with Femara or Gleevec

          -  Uncontrolled endocrine disorders such as diabetes mellitus, confirmed hypo- or
             hyperthyroidism, Cushing's syndrome, Addison's disease (treated or untreated)

          -  Patients with unstable angina, or uncontrolled cardiac disease (e.g. class III or IV
             New York Heart Association's functional classification)

          -  Other concurrent malignant disease with the exception of cone-biopsied in situ
             carcinoma of the cervix uteri, or adequately treated basal or squamous cell carcinoma
             of the skin, or other curable cancers e.g. Hodgkin's disease or non-Hodgkin lymphoma
             (NHL), provided 5 years have elapsed from completion of therapy, and there has been no
             recurrence

          -  Concomitant treatment with steroids, e.g. glucocorticoids for indications other than
             cancer, except aerosol for obstructive airways diseases and steroid injection to the
             joints for treatment of inflammation

          -  Other investigational drugs within the past 3 weeks and the concomitant use of
             investigational drugs

          -  History of non-compliance to medical regimens and patients who are considered
             potentially unreliable

          -  Patients with known brain metastasis

          -  Patients with known chronic liver disease (i.e., chronic active hepatitis, and
             cirrhosis)

          -  Patients with known diagnosis of human immunodeficiency virus (HIV) infection

          -  Patients who received chemotherapy within 4 weeks (6 weeks for nitrosourea or
             mitomycin-C) prior to study entry, unless the disease is rapidly progressing

          -  Patients who previously received radiotherapy to greater than or equal to 25% of the
             bone marrow

          -  Patients who had a major surgery within 2 weeks prior to study entry