Patient case: 73-year-old female with breast cancer; genetic feature: CDKN2A

Clinical trial: Letrozole (Femara) Plus Imatinib Mesylate (Gleevec) for Breast Cancer Patients

Summary: The goal of this clinical research study is to learn if the combination of Femara (letrozole) and Gleevec (imatinib mesylate) can shrink or slow the growth of the tumor in patients who have hormonal sensitive advanced breast cancer.
  Primary Objectives:
  -  To determine the efficacy of Letrozole plus Imatinib Mesylate in patients with ER and or PgR positive metastatic breast cancer. Efficacy will be measured by the rate of clinical tumor response.
  -  To determine the safety and tolerability of Letrozole plus Imatinib Mesylate in patients with metastatic breast cancer.
  -  To determine the time to disease progression and overall survival in patients with metastatic breast cancer who are treated with Letrozole plus Imatinib Mesylate.

Detailed description: Letrozole is an antihormonal drug used in the standard treatment of advanced hormonal sensitive breast cancer. Imatinib mesylate is a drug (not chemotherapy) 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.
  Before the treatment starts, you will have blood tests (2-4 teaspoons), CT scans of your chest and abdomen, and a bone scan. Blood tests (2-4 teaspoons) will be repeated every week for 4 weeks and then every month for the length of the study. The blood tests are done to evaluate how the drug affects breast cancer related markers in the blood. These blood tests will be done at screening, and then at Months 2 and 4. The CT scans will be repeated every 2 months as is standard for your care.
  You will take letrozole once a day by mouth and imatinib mesylate twice a day by mouth until intolerable side effects occur or until your tumor grows further. You will stop the treatment if your tumor grows or intolerable side effects occur.
  This is an investigational study. Letrozole is FDA approved for the treatment of advanced breast cancer and is commercially available. Imatinib mesylate is approved for chronic myelogenous leukemia and is being investigated for use in the treatment of breast cancer. A total of 45 patients will take part in this study. All will be enrolled at M. D. Anderson.

Eligibility: Inclusion Criteria:
  1. 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.
  2. Patients must have documented expression of either PDGFR or CD117 (c-kit) by immunohistochemistry.
  3. 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.
  4. 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 (LH and FSH levels greater than 40 IU/L ) or postmenopausal estradiol levels ( less than 5mg/dl) or according to the definition of "postmenopausal range" for the laboratory involved bilateral oophorectomy.
  5. Performance status, ECOG greater than or equal to 2.
  6. 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.
  7. Adequate bone marrow function (ANC = 1.5 x 10 to the 9th power/L and platelets greater than or equal to 100.0 x10 to the 9th power/L, and hemoglobin greater than 10.0 g/dL).
  8. Adequate renal function (creatinine less than 1.5 mg/dl) and hepatic function (T. Bilirubin less than 1.5 x normal, AST less than 2.5 x normal)
  9. A life expectancy of at least 6 months.
  10. 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).
  11. Ability to understand and the willingness to sign a written informed consent.
  Exclusion Criteria:
  1. Prior treatment with Femara or Gleevec.
  2. Uncontrolled endocrine disorders such as diabetes mellitus, confirmed hypo- or hyperthyroidism, Cushing's Syndrome, Addison's disease (treated or untreated).
  3. Patients with unstable angina, or uncontrolled cardiac disease (e.g. Class III or IV New York Heart Association's Functional Classification).
  4. 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 NHL, provided 5 years have elapsed from completion of therapy, and there has been no recurrence.
  5. 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.
  6. Other investigational drugs within the past 3 weeks and the concomitant use of investigational drugs.
  7. History of non-compliance to medical regimens and patients who are considered potentially unreliable.
  8. Patients with known brain metastasis.
  9. Patients with known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
  10. Patients with known diagnosis of human immunodeficiency virus (HIV) infection.
  11. Patients who received chemotherapy within 4 weeks (6 weeks for nitrosourea or mitomycin-C) prior to study entry, unless the disease is rapidly progressing.
  12. Patients who previously received radiotherapy to greater than or equal to 25% of the bone marrow.
  13. Patients who had a major surgery within 2 weeks prior to study entry.

Relevance to patient case: not relevant