Lapatinib in Combination With Radiation Therapy in Patients With Brain Metastases From HER2-Positive Breast Cancer
Condition: Breast Cancer; Brain Metastases
MeSH terms: Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms
Intervention: Lapatinib; Whole Brain Radiation; Herceptin
Intervention description: Orally twice daily; 15 treatments over a period of 3 weeks; Herceptin 4mg/kg loading dose then 2 mg/kg IV once weekly, then once every three weeks after cycle 3.
Intervention MeSH terms: Trastuzumab; Lapatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Herceptin; breast cancer; radiation therapy; stereotactic radiosurgery; SRS; whole brain radiation; WBRT

Summary:

      The purpose of this research study is to determine the safety of combining lapatinib plus
      radiation in patients with breast cancer that has spread to the brain. Depending upon the
      participants cancer, they may also have stereotactic radiosurgery (SRS). Lapatinib s a
      compound that may stop cancer cells from growing abnormally. It is thought that lapatinib
      might also make cancer cells more sensitive to radiation. This drug has been used in other
      research studies in women with breast cancer, and information from those other research
      studies suggests that lapatinib may help to shrink or stabilize breast tumors both inside the
      brain and outside the brain.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically-confirmed invasive breast cancer

          -  HER2 overexpressing breast cancer defined as 3+ staining by immunohistochemistry, or
             HER2 gene amplification by FISH

          -  At least one parenchymal brain metastasis

          -  Disease progression in the CNS as assessed by at least one of the following; new
             neurological signs or symptoms; new lesion(s) in the CNS on an imaging study;
             progressive lesions on an imaging study

          -  At least two weeks since prior radiotherapy, last chemotherapy, immunotherapy,
             biologic therapy, or major surgery for cancer

          -  18 years of age or older

          -  Life expectancy of greater than 12 weeks

          -  ECOG performance status 0-2

          -  Normal organ and marrow function as described in the protocol

          -  Left ventricular ejection fraction > 50%

          -  Able to swallow and retain oral medications

        Exclusion Criteria:

          -  Prior WBRT

          -  Receiving any other investigational agents

          -  Concurrent chemotherapy, immunotherapy, biologic therapy or hormonal therapy for
             treatment of their cancer

          -  History of grade 3 or 4 allergic reactions attributed to compounds of similar chemical
             or biologic composition to herceptin or lapatinib

          -  Leptomeningeal carcinomatosis as the only site of CNS involvement

          -  Concurrent treatment with medications that are either inducers of inhibitors of CYP3A4

          -  Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel or active ulcerative colitis

          -  History of immediate or delayed hypersensitivity reaction to gadolinium contrast
             agents

          -  Other known contraindication to MRI

          -  Uncontrolled intercurrent illness

          -  History of other active malignancy except curatively treated basal cell carcinoma or
             squamous cell carcinoma of the skin, or carcinoma in situ of the cervix

          -  Pregnant or breastfeeding women