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

• Status: Completed
• Trial end date: 2020-03-04
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Daiichi Sankyo, Inc.; Plexxikon
• Collaborator: Plexxikon
• Treatments: Dacarbazine; Temozolomide

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.