A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma
Condition: Recurrent Glioblastoma
MeSH terms: Glioblastoma; Recurrence
Intervention: PLX3397
Intervention description: Capsules administered once or twice daily, continuous dosing
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glioblastoma; brain cancer

Summary:

      The objective of this study is to evaluate the response of subjects with recurrent
      glioblastoma to continuous therapy of PLX3397.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients ≥18 years old with a life expectancy of at least 8 weeks

          -  Radiographically proven recurrent (≥ first relapse), intracranial Glioblastoma (GBM)

          -  For all patients, availability of at least 10 unstained slides (or archival tumor
             block sufficient to generate at least 10 unstained slides) from any previous GBM
             surgery

          -  Previous treatment with external beam radiation and temozolomide chemotherapy

          -  Before the first dose of PLX3397,adequate recovery from toxicity of prior therapy as
             follows:

        >28 days for cytotoxic therapy >42 days for nitrosoureas >28 days for bevacizumab >7 days
        for non cytotoxic therapy such as interferon, tamoxifen, thalidomide, cis-retinoic acid, or
        erlotinib

          -  Women of child-bearing potential must have a negative pregnancy test within 7 days of
             initiation of dosing and must agree to use an acceptable method of birth control while
             on study drug and for 3 months after the last dose. Women of non-childbearing
             potential may be included if they are either surgically sterile or have been
             postmenopausal for ≥1 year. Men of child-bearing potential must also agree to use an
             acceptable method of birth control while on study drug.

          -  Karnofsky performance status of ≥60

          -  Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.0 x
             109/L, Hgb >9 g/dL, platelet count ≥50 x 109/L, Aspartate aminotransferase/Alanine
             aminotransferase (AST/ALT) ≤2.5x Upper Limit of Normal (ULN), creatinine ≤1.5x ULN)

          -  Willing and able to provide written informed consent prior to any study related
             procedures and to comply with all study requirements

        Exclusion Criteria:

          -  Investigational drug use within 28 days of the first dose of PLX3397

          -  GBM progression within 3 months of previous radiation by Response Assessment in
             Neuro-Oncology (RANO) criteria

          -  History of Grade 2 Common Toxicity Criteria for Adverse Events (CTCAE v4) or greater
             acute intracranial hemorrhage

          -  Previous failure of bevacizumab or other vascular endothelial growth factor (VEGF)
             therapy except in a first line setting

          -  History of malignant glioma with co-deletion of 1p/19q

          -  A concurrent active cancer that requires non-surgical therapy (e.g. chemotherapy,
             radiation, adjuvant therapy). Prior history of other cancer is allowed, as long as
             there was no active disease within the prior 3 years.

          -  Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel
             resection that would preclude adequate absorption

          -  Patients with serious illnesses, uncontrolled infection, medical conditions, or other
             medical history including abnormal laboratory results, which in the investigator's
             opinion would be likely to interfere with a patient's participation in the study, or
             with the interpretation of the results

          -  Women of child-bearing potential who are pregnant or breast feeding

          -  corrected QT interval (QTc) ≥450 msec at Screening