A Phase 1b/2 Study of PLX3397 + Radiation Therapy + Temozolomide in Patients With Newly Diagnosed Glioblastoma
Phase: Phase 1/Phase 2
Diagnosis: Brain/Neuro Cancer: Newly Diagnosed
NCT ID: NCT01790503
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 13-247
The study objectives are to assess the potential for PLX3397 to improve the efficacy of standard of care radiation therapy (RT) + temozolomide in patients with newly diagnosed glioblastoma (GBM).
Dana-Farber Cancer Institute, Brigham and Women's Hospital
David Reardon, MD,
Dana Farber Cancer Institute
Dana-Farber Cancer Institute:
- Male or female patients ≥18 years old.
- Histologically confirmed definitive GBM or gliosarcoma by partial or complete
surgical resection (i.e. not by biopsy only) within 5 weeks prior to PLX3397
administration (C1D1). Tumor must have a supratentorial component. For all patients,
availability of a surgical paraffin tumor block sufficient to generate at least 20
unstained slides; or, if a paraffin tumor block is unavailable, at least 20 unstained
- The patient must have recovered from the effects of surgery, post-operative
infection, and other complications before study registration.
- A diagnostic contrast-enhanced MRI or CT scan of the brain must be performed
preoperatively and postoperatively prior to the initiation of radiotherapy, within 28
days (preferably 14 days) prior to C1D1.
- Patients unable to undergo MR imaging because of non-compatible devices can be
enrolled, provided pre- and post-operative contrast-enhanced CT scans are obtained
and are of sufficient quality.
- Patients must receive RT at the participating institution.
- Women of child-bearing potential must have a negative pregnancy test within 14 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, and for 3 months after the
- Karnofsky performance status of ≥70.
- Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.5x
109/L, Hgb >10 g/dL, platelet count ≥100 x 109/L, AST/ALT ≤2.5x ULN, creatinine ≤1.5x
- Willing and able to provide written informed consent prior to any study related
procedures and to comply with all study requirements.
- Evidence of recurrent GBM or metastases detected outside of the cranial vault.
- Investigational drug use within 28 days of the first dose of PLX3397 or concurrently.
- Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment.
- Prior radiation or chemotherapy for glioblastoma or glioma.
- Prior chemotherapy or radiosensitizers for cancer of the head and neck (except for T1
glottic cancer) that would result in an overlap of radiation fields.
- Prior allergic reaction to temozolomide.
- History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage.
- Active cancer (either concurrent or within the last 3 years) that requires
non-surgical therapy (e.g. chemotherapy or radiation therapy), with the exception of
surgically treated basal or squamous cell carcinoma of the skin, melanoma in-situ, or
carcinoma in-situ of the cervix.
- Chronic active hepatitis B or C.
- Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel
resection that would preclude adequate absorption of study drug.
- 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.
- At Screening QTcF ≥450 msec for males and ≥470 msec for females.