A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma

NCT01349036 | Terminated Phase 2 Results

• 1 other identifier: PLX108-04
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Recurrent Glioblastoma

Keywords

Glioblastoma; brain cancer

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (1)

• 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

Study Arms (2)

PLX3397-Cohort 1

EXPERIMENTAL

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.

Drug: PLX3397

PLX3397-Cohort 2

EXPERIMENTAL

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

Drug: PLX3397

Interventions

PLX3397 DRUG

Capsules administered once or twice daily, continuous dosing

Also known as: Pexidartinib

PLX3397-Cohort 1; PLX3397-Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Plexxikon: collaborator

Study Sites (6)

University California, Los Angeles

Los Angeles, California, 90095, United States

Location

University California, San Francisco

San Francisco, California, 94143, United States

Location

Dana Faber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related 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.

  PMID: 18356283 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

pexidartinib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Study Director
• Organization: Daiichi Sankyo Inc.

CTRinfo@dsi.com

908-992-6400

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2011
• First Posted: May 6, 2011
• Study Start: December 3, 2011
• Primary Completion: November 5, 2013
• Study Completion: November 5, 2013
• Last Updated: March 3, 2020
• Results First Posted: January 9, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (6)