Brain Mets - Capecitabine Plus Sunitinib and WBRT
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: sunitinib; capecitabine; WBRT
Intervention description: Sutent; concurrently; Whole Brain Radiotherapy 30 Gy in 10 fractions
Intervention MeSH terms: Capecitabine; Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: brain metastasis; breast cancer; metastatic breast cancer

Summary:

      The purpose of this study is to assess the efficacy and safety of concurrent whole brain
      radiotherapy (WBRT) and capecitabine followed by combination capecitabine and sunitinib in
      treating patients with CNS metastases from breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients must be age 18 or older. Histological or cytologically confirmed invasive breast
        cancer, with Stage IV disease.

        Evidence of radiographically measurable CNS metastases (greater than or equal to 10mm on
        T1-weighted gadolinium-enhanced MRI) within 2 weeks prior to starting treatment. Patients
        without known extra-CNS disease are eligible.

        Must have metastases in the brain. Patients with concurrent leptomeningeal carcinomatosis
        are eligible for the study. Local radiation to sites of meningeal involvement in the spine
        is allowed.

        No prior whole brain radiation. Patients who had previous stereotactic brain irradiation
        are eligible, provided they have new measurable brain lesions (which has not been radiated
        previously) and will receive WBRT at 30Gy over 10 fractions.

        May undergo surgical resection of CNS metastases if clinically indicated, but must have
        remaining measurable disease in the brain after surgery.

        No prior treatment with capecitabine in the adjuvant or metastatic settings. Patients may
        have completed 5-fluorouracil based treatment in the adjuvant setting or metastatic setting
        more than one year prior.

        Patients who had previous trastuzumab therapy will be eligible but treatment will be
        discontinued prior to enrollment.

        Cardiac ejection fraction within institutional range of normal as measure by echocardiogram
        or MUGA scans at baseline.

        Hematological adequacy Hepatic adequacy Renal adequacy Must have recovered from toxicity of
        prior chemotherapy with laboratory values as specified above. Concurrent treatment with
        bisphosphonates is permitted. Performance status of ECOG 0-1.

        Life expectancy of at least 12 weeks. At least 3 weeks since major surgical procedures.
        Able to swallow and retain oral medication.

        Exclusion Criteria:

        Pregnant or breast feeding. Known allergy to capecitabine or 5-fluorouracil. Known to have
        dihydropyrimidine dehydrogenase (DPD) deficiency.

        Patients who have leptomeningeal carcinomatosis as the only site of CNS metastases.

        Patients taking concomitant medications which are CYP3A4 inhibitors or inducers.

        Patients who will receive intrathecal chemotherapy for leptomeningeal disease. Patients
        with psychiatric or addictive disorders that would adversely effect compliance with oral
        medication.

        Life expectancy less than 3 months. Symptomatic lymphangitic spread to lung. Malabsorption
        syndrome, disease significantly affecting gastrointestinal function, or resection of the
        stomach or small bowel.

        History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents, or
        other contraindication or gadolinium contrast.

        Other known contraindication to MRI, such as a cardiac pacemaker, implanted cardiac
        defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel,

        1Vascular disease within 12 months prior to enrollment Uncontrolled infection History of
        other malignancy, except for curatively treated basal cell carcinoma or squamous cell
        carcinoma of the skin, or carcinoma in situ of the cervix. Subjects with other malignancies
        who have been disease-free for at least 5 years are eligible