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An Open Label Phase 1b/2 Study of Orally Administered PLX3397 in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

Phase 1/Phase 2
18 Years
Not Enrolling
Patients With Newly Diagnosed Glioblastoma

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Trial Information

An Open Label Phase 1b/2 Study of Orally Administered PLX3397 in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

Inclusion Criteria:

- 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 screening. Tumor
must have a supratentorial component. For all patients, availability of a surgical
tumor block sufficient to generate at least 20 unstained slides.

- The patient must have recovered from the effects of surgery, post-operative
infection, and other complications before study registration.

1. 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 prior to C1D1.

2. 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
last dose.

- 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.

Exclusion Criteria:

- 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.

- Previous hepatitis B or C infection.

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase 1b dose escalation: Identification of Recommended Phase 2 Dose (RP2D)

Outcome Description:

A total of approximately 7 patients will be enrolled in each dose level. The starting dose level of PLX3397 will be 800 mg/day, using a twice daily (BID) dosing regimen. If that dose level is tolerated, the next dose level to be tested will be 1000 mg/day, which is the RP2D for single agent PLX3397 in solid tumors. Lower doses may be explored, if required. These lower doses are planned to be 600 mg/day (if PLX3397 is not tolerated at 800 mg/day) and 400 mg/day (if PLX3397 is not tolerated at 600 mg/day). Conversely, if the dose level of 1000 mg/day is tolerated, higher dose levels of PLX3397 may be investigated, at up to 50% increments, depending on the observed pharmacokinetics (PK) and toxicities.

Outcome Time Frame:

1 year

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

May 2013

Completion Date:

December 2015

Related Keywords:

  • Patients With Newly Diagnosed Glioblastoma
  • glioblastoma
  • GBM
  • Glioblastoma



Huntsman Cancer Institute University of Utah Salt Lake City, Utah  84132