A Phase 1b/2 Study of PLX3397 + Radiation Therapy + Temozolomide in Patients With Newly Diagnosed Glioblastoma

Status: Recruiting
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).


Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital, Beth-Israel Deaconess Medical Center, Beth-Israel Deaconess Medical Center

Overall PI:
David Reardon, MD, Dana Farber Cancer Institute

Site-responsible Investigators:

Dana-Farber Cancer Institute: Lisa Doherty, ldoherty1@partners.org

Eligibility Criteria

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 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 slides. - 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 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 ULN). - 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. - 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.
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