Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Brain Neoplasms

Disease Attributes

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

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.

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

Capsules administered once or twice daily, continuous dosing

PLX3397

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

A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma

A Phase 2 Study of Orally Administered PLX3397 in Patients With Recurrent Glioblastoma

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Response to treatment was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria. All participants were evaluated for progression free survival (PFS), and overall survival (OS). The six-month PFS rate was defined as the number of subjects with PFS of at least 6-month duration, with PFS measured from the first day of treatment (Cycle 1, Day 1) to the date of the first documented disease progression or date of death, whichever occurs first, over a 6-month period and evaluated using the Kaplan Meier method. The rate of OS was defined as the number of subjects that survived until study exit.

A noncompartmental method of analysis was used to analyze the plasma concentrations of PLX3397. Mean plasma pharmacokinetic parameters, include time to maximum concentration (Tmax) and will be calculated from the Cycle 1, Day 15 values.

A noncompartmental method of analysis was used to analyze the plasma concentrations of PLX3397. Mean plasma pharmacokinetic parameters include maximum concentration (Cmax) and will be calculated from the Cycle 1, Day 15 values.

A noncompartmental method of analysis was used to analyze the plasma concentrations of PLX3397. Mean plasma pharmacokinetic parameters include an assessment of area under the curve over 0-4 hours (AUC0-4), and will be calculated from the Cycle 1, Day 15 values.

A noncompartmental method of analysis was used to analyze the plasma concentrations of PLX3397. Mean plasma pharmacokinetic parameters include an assessment of area under the curve over 0-6 hours (AUC0-6), and will be calculated from the Cycle 1, Day 15 values.

Plexxikon

Daiichi Sankyo

Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.

Participants with recurrent glioblastoma who required reoperation were treated with PLX3397 for 7 days prior to surgery.

PLX3397 - Cohort 1 (Surgical)

Participants who received PLX3397 continuously on 28 day cycles.

PLX3397 - Cohort 2 (Non-surgical)

Participants with recurrent glioblastoma who received PLX3397 continuously on 28 day cycles.

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Study was terminated due to results noted in primary outcome measure 1. The sponsor felt that the PFS 6 goal of 25% (Lamborn, 2008) was unlikely to be met upon further enrollment.

Study Director

Six-month PFS rate

Overall survival

Complete response rate

Partial response rate

Stable disease rate

Progressive disease rate

Not Evaluable

Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 1 (surgical).

Surgical Cohort 1 (N=14)

Participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 2 (non-surgical).

Non-Surgical Cohort 2 (N=24)

Response rates were assessed in the modified intent-to-treat population.

Summary of Response Rates in Participants on Treatment With PLX3397

Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15

Any Event

Fatigue

Constipation

Nausea

Hair color changes

Aspartate aminotransferase increased

Alanine aminotransferase increased

Decreased appetite

Headache

Pyrexia

Dry Mouth

Rash

Neutropenia

Lymphopenia

Blood Lactate Dehydrogenase Increased

Hypertension

All participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 1 (surgical).

All participants with recurrent glioblastoma who were treated with PLX3397 in Cohort 2 (non-surgical).

Safety events were assessed in the Safety Population.

Incidence (Number and Percentage of Participants) With Treatment-Emergent Adverse Events Related to Study Drug Occurring in ≥10% Participants During Treatment With PLX3397 (Safety Population)

Spots Global Cancer Trial Database for A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial