A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma

Recurrent Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01349036
• Other study ID #: PLX108-04
• Status: Terminated
• Phase: Phase 2
• Start date: December 3, 2011
• Est. completion date: November 5, 2013

Study information

• Verified date: February 2020
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 38
• Est. completion date: November 5, 2013
• Est. primary completion date: November 5, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma
• Recurrent Glioblastoma

Intervention

Drug:
• PLX3397
Capsules administered once or twice daily, continuous dosing

Locations

Country	Name	City	State
United States	Dana Faber Cancer Institute	Boston	Massachusetts
United States	University of Texas, MD Anderson Cancer Center	Houston	Texas
United States	University California, Los Angeles	Los Angeles	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Huntsman Cancer Institute University of Utah	Salt Lake City	Utah
United States	University California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.	Plexxikon

Country where clinical trial is conducted

United States, 

References & Publications (1)

Lamborn KR, Yung WK, Chang SM, Wen PY, Cloughesy TF, DeAngelis LM, Robins HI, Lieberman FS, Fine HA, Fink KL, Junck L, Abrey L, Gilbert MR, Mehta M, Kuhn JG, Aldape KD, Hibberts J, Peterson PM, Prados MD; North American Brain Tumor Consortium. Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas. Neuro Oncol. 2008 Apr;10(2):162-70. doi: 10.1215/15228517-2007-062. Epub 2008 Mar 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Summary of Response Rates in Participants on Treatment With PLX3397	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.	6 months post dose
Primary	Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15	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.	Pre-dose and up to 6 post dose during cycle 1, Day 15
Primary	Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15	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.	Pre-dose and up to 6 post dose during cycle 1, Day 15
Primary	Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15	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.	Pre-dose and up to 6 post dose during cycle 1, Day 15
Primary	Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15	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.	Pre-dose and up to 6 post dose during cycle 1, Day 15
Secondary	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)		Up to 1 year post dose