A Phase 2 Study of Orally Administered PLX3397 in Patients With Recurrent Glioblastoma
Inclusion Criteria:
- Male or female patients ≥18 years old with a life expectancy of at least 8 weeks
- Radiographically proven recurrent (≥ first relapse), intracranial 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, AST/ALT ≤2.5x 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 RANO criteria
- History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage
- Previous failure of bevacizumab or other 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
- QTc ≥450 msec at Screening