A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma

Daiichi Sankyo

Status and phase: Terminated; Phase 2

Conditions: Recurrent Glioblastoma

Treatments: Drug: PLX3397

Study type: Interventional

Funder types: Industry

Identifiers

NCT01349036

PLX108-04

Details and patient eligibility

About

The objective of this study is to evaluate the response of subjects with recurrent glioblastoma to continuous therapy of PLX3397.

Enrollment: 38 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female patients ≥18 years old with a life expectancy of at least 8 weeks
• Radiographically proven recurrent (≥ first relapse), intracranial Glioblastoma (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, Aspartate aminotransferase/Alanine aminotransferase (AST/ALT) ≤2.5x Upper Limit of Normal (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 Response Assessment in Neuro-Oncology (RANO) criteria
• History of Grade 2 Common Toxicity Criteria for Adverse Events (CTCAE v4) or greater acute intracranial hemorrhage
• Previous failure of bevacizumab or other vascular endothelial growth factor (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
• corrected QT interval (QTc) ≥450 msec at Screening

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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38 participants in 2 patient groups

PLX3397-Cohort 1

Experimental group

Description:

10 patients with recurrent glioblastoma who require reoperation will be treated with PLX3397 for 7 days prior to surgery and their tumor tissue will be evaluated for pharmacokinetic levels and pharmacodynamic effects.

Treatment:

Drug: PLX3397

PLX3397-Cohort 2

Experimental group

Description:

30 patients will be orally dosed with PLX3397 continuously on 28 day cycles.

Treatment:

Drug: PLX3397