Lapatinib in Women With Metastatic Breast Cancer Who Have Failed Prior Antihormone Therapy
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: lapatinib
Intervention description: lapatinib 1500 mg PO daily
Intervention MeSH terms: Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: breast cancer; hormone receptor positive; HER-2 negative

Summary:

      Hormone receptor positive breast cancer is the most common type of breast cancer, comprising
      70-80% of all breast cancers. Endocrine therapy is the main type of initial treatment for
      patients with your type of breast cancer. Endocrine therapy is treatment that tries to
      remove, or block certain hormones from binding to the cancer cells and thus slow or stop the
      growth of cancer. Although most patients with your type of breast cancer respond initially to
      endocrine therapies, it can lose its effectiveness. New therapies for this type of cancer are
      needed.
    

Eligibility criteria:

        Inclusion Criteria

          -  Histologically or cytologically confirmed invasive breast cancer, which at time of
             study entry is either stage III (locally advanced) disease not amenable to curative
             therapy or stage IV disease. Histological confirmation of recurrent/metastatic disease
             is encouraged but not required if clinical evidence of stage IV disease recurrence is
             available.

          -  ER and/or Progesterone Receptor (PgR )positive breast cancer (10% or more of
             infiltrating cancer cells exhibit nuclear staining for ER and/or PgR)

          -  Have had progressive disease or development of new metastatic disease while on
             treatment or within 12 months of treatment with an aromatase inhibitor and/or
             Fulvestrant in adjuvant or metastatic setting

          -  Have measurable (defined as at least 1 lesion that can be accurately measured in at
             least 1 dimension [longest diameter to be recorded], with minimum lesion size ≥ 2cm on
             conventional measurement techniques or ≥ 1cm on spiral computed tomography [CT] scan),
             or evaluable disease. Patients with lytic or blastic bone disease as only site of
             disease will be eligible for the study. These patients will be evaluable for
             progression but not for response.

          -  Primary tumor was HER-2 negative (IHC 0 or IHC 1+/2+ and Fluorescence in situ
             hybridization [FISH] ≤ 1.9)

          -  Patients could have received prior Tamoxifen either as adjuvant therapy or for stage
             IV disease

          -  Performance status of 2 or better per Eastern Cooperative Oncology Group (ECOG)
             criteria

          -  Adequate cardiac function (cardiac ejection fraction ≥ 50% as measured by
             echocardiogram or multigated acquisition (MUGA) scan).

          -  IV bisphosphonate and denosumab for bony metastatic disease will be allowed

          -  Palliative radiation therapy to bony metastases will be allowed

          -  Adequate bone marrow function per good medical practice. Results of these tests do not
             determine eligibility. Minor deviations are acceptable if they do not impact safety in
             the judgment of the treating physician. Absolute neutrophil count (ANC) ≥ 1500/mm3,
             platelet count ≥ 100,000/mm3, and hemoglobin ≥ 10 g/dL

          -  Adequate kidney function: serum creatinine of ≤ 1.5mg/dl and/or creatinine clearance
             of ≥ 60 mL/min

          -  Adequate hepatic function: transaminases < 2 x upper limit of normal and total
             bilirubin ≤ 1.5 mg/dL.

          -  Must have a serum albumin ≥ 3.0 g/dL.

          -  Must be informed of investigational nature of study and must sign informed consent in
             accordance with institutional rules.

          -  Pretreatment lab values must be performed within 14 days of patient registration and
             other baseline studies within 30 days.

          -  Patients will have a baseline bone scan, Computerized Tomography (CT) chest, abdomen
             and pelvis or Positron Emission Tomography (PET)/CT.

          -  If previously treated brain metastasis and free of central nervous system (CNS)
             symptoms and > 3 months from treatment of brain metastasis are eligible

        Exclusion Criteria

          -  Prior HER-2 targeted therapy for metastatic disease

          -  Has uncontrolled brain metastasis or leptomeningeal disease

          -  Has rapidly progressing and/or bulky disease which in the opinion of the investigator
             may be more appropriately treated with a chemotherapy-based strategy.

          -  Has an uncontrolled intercurrent illness including, but not limited to ongoing or
             active infection requiring parenteral antibiotics or psychiatric illness/social
             situations that would limit compliance with study requirements.

          -  Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors

          -  Patients with GI tract disease resulting in an inability to take oral medication,
             malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures
             affecting absorption, uncontrolled inflammatory GI disease (eg, Crohn's, ulcerative
             colitis).

          -  Current active hepatic or biliary disease (exception of patients with Gilbert's
             syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease
             per investigator assessment)

          -  Renal function as measured by creatinine clearance <3 0ml/min (ratio to norm < 0.1)

          -  HIV-positive patients receiving combination antiretroviral therapy

          -  Pregnant women

          -  Active cardiac disease defined as:

               -  History of uncontrolled or symptomatic angina

               -  History of arrhythmias requiring medications, or clinically significant, with the
                  exception of asymptomatic atrial fibrillation requiring anticoagulation

               -  Myocardial infarction < 6 months from study entry

               -  Uncontrolled or symptomatic congestive heart failure

               -  Ejection fraction below institutional normal limit

               -  Any other cardiac condition, which in the opinion of treating physician, would
                  make this protocol unreasonably hazardous for the patient

          -  History of another primary cancer, with exception of:

               -  curatively resected nonmelanomatous skin cancer

               -  curatively treated cervical carcinoma in-situ

               -  other primary solid tumor curatively resected treated with no known active
                  disease present and no treatment administered for the last 3 years.

          -  Life expectancy of < 2 months