Whole-Brain Radiation Therapy or Stereotactic Radiosurgery With or Without Lapatinib Ditosylate in Treating Patients With Brain Metastasis From HER2-Positive Breast Cancer
Condition: HER2-Positive Breast Carcinoma; Invasive Breast Carcinoma; Metastatic Malignant Neoplasm in the Brain; Recurrent Breast Carcinoma; Stage IV Breast Cancer AJCC v6 and v7
MeSH terms: Carcinoma; Breast Neoplasms; Brain Neoplasms; Neoplasms
Intervention: Laboratory Biomarker Analysis; Lapatinib Ditosylate; Stereotactic Radiosurgery; Whole-Brain Radiotherapy
Intervention description: Correlative studies; Given PO; Undergo SRS; Undergo WBRT
Intervention MeSH terms: Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 143.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well whole-brain radiation therapy or stereotactic
      radiosurgery with or without lapatinib ditosylate works in treating patients with breast
      cancer that has too many of a protein called human epidermal growth factor receptor 2 (HER2)
      on its cells and has spread to the brain. Radiation therapy uses high energy x rays to kill
      tumor cells and shrink tumors. Stereotactic radiosurgery is a specialized radiation therapy
      that delivers a single, high dose of radiation directly to the tumor and may kill more tumor
      cells and cause less damage to normal tissue. Lapatinib ditosylate may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known
      whether whole-brain radiation therapy or stereotactic radiosurgery together with lapatinib
      ditosylate is an effective treatment for brain metastasis from breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically (histologically or cytologically) proven diagnosis of invasive breast
             cancer

          -  HER2-overexpressing breast cancer (3+ staining by immunohistochemistry or HER2 gene
             amplification by fluorescent in situ hybridization [FISH] or silver in situ
             hybridization [SISH] >= 2.0)

          -  At least 1 measurable unirradiated parenchymal brain metastasis within 21 days prior
             to study entry; patients who are to undergo SRS must have no more than 10 brain
             metastases; there is no limit on number of brain metastases for WBRT; the minimum size
             as measured on T1-weighted gadolinium-enhanced MRI must be as follows according to the
             number of brain metastases:

               -  For a single solitary lesion the size must be >= 10 mm

               -  For 2 or more lesions, the size of at least 2 of the lesions must be >= 5 mm

               -  Patients may also have the following provided the size requirements above are
                  met:

                    -  Progressive parenchymal brain metastasis following stereotactic radiosurgery
                       for 1-3 brain metastases, with at least 1 new measurable brain lesion

                    -  Progressive parenchymal brain metastasis following surgical resection of 1-3
                       brain metastases, with at least 1 measurable brain lesion

          -  History/physical examination within 21 days prior to study entry

          -  Karnofsky performance status >= 60 within 21 days prior to study entry

          -  Able to swallow and retain oral medication (note: for patients unable to swallow
             tablets, an oral suspension preparation is acceptable)

          -  Absolute neutrophil count (ANC) >= 1,200 cells/mm^3 (within 21 days prior to study
             entry)

          -  Platelets >= 70,000 cells/mm^3 (within 21 days prior to study entry)

          -  Hemoglobin >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve
             hemoglobin [Hgb] >= 8.0 g/dL is acceptable) (within 21 days prior to study entry)

          -  Creatinine < 1.5 times institutional upper limit of normal (within 21 days prior to
             study entry)

          -  Bilirubin < 1.5 times institutional upper limit of normal (within 21 days prior to
             study entry)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 times
             institutional upper limit of normal with or without liver metastasis (within 21 days
             prior to study entry)

          -  Patient must provide study specific informed consent prior to study entry

          -  Women of childbearing potential must have a negative serum pregnancy test within 21
             days prior to study entry

          -  Sexually active women of childbearing potential and sexually active men must practice
             adequate contraception during therapy and for 12 months after protocol treatment
             completion

          -  Prior lapatinib is allowed as long as the last dose received was > 21 days prior to
             study entry and provided the patient has not received it at any time after the
             diagnosis of brain metastasis

        Exclusion Criteria:

          -  Prior WBRT

          -  Prior radiation therapy (RT) (any site) with concurrent lapatinib defined as 1 or more
             days on which the patient received both radiation therapy and lapatinib on the same
             day

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Prior invasive malignancy (except non-melanomatous skin cancer, curatively resected
             thyroid papillary carcinoma, and invasive and non-invasive cancers related to the
             breast cancer) unless disease free for a minimum of 3 years

          -  Leptomeningeal disease

          -  Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiation therapy fields except patients who have progressed following stereotactic
             radiosurgery for 1-3 brain metastases, with at least one new lesion

          -  Severe, active co-morbidity, defined as follows:

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last 6 months

               -  Transmural myocardial infarction within the last 6 months

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of study entry

               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy at the time of study entry

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
                  hepatic or biliary disease that is acute or currently active or that requires
                  antiviral therapy (with the exception of patients with Gilbert's syndrome,
                  asymptomatic gallstones, liver metastases, or stable chronic liver disease per
                  investigator assessment)

               -  History of left ventricular ejection fraction (LVEF) below institutional normal
                  unless repeated and within institutional normal range within 90 days of study
                  entry

          -  Grade 2 or greater rash of any cause at time of study entry

          -  Grade 2 or greater diarrhea of any cause at time of study entry