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A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01349036
Recruitment Status : Terminated (Business Decision)
First Posted : May 6, 2011
Results First Posted : January 9, 2020
Last Update Posted : March 3, 2020
Sponsor:
Collaborator:
Plexxikon
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

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

Condition or disease Intervention/treatment Phase
Recurrent Glioblastoma Drug: PLX3397 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Orally Administered PLX3397 in Patients With Recurrent Glioblastoma
Actual Study Start Date : December 3, 2011
Actual Primary Completion Date : November 5, 2013
Actual Study Completion Date : November 5, 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PLX3397-Cohort 1
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
Capsules administered once or twice daily, continuous dosing
Other Name: Pexidartinib

Experimental: PLX3397-Cohort 2
30 patients will be orally dosed with PLX3397 continuously on 28 day cycles.
Drug: PLX3397
Capsules administered once or twice daily, continuous dosing
Other Name: Pexidartinib




Primary Outcome Measures :
  1. Summary of Response Rates in Participants on Treatment With PLX3397 [ Time Frame: 6 months post dose ]
    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.

  2. Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15 [ Time Frame: Pre-dose and up to 6 post dose during 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.

  3. Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15 [ Time Frame: Pre-dose and up to 6 post dose during 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.

  4. Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15 [ Time Frame: Pre-dose and up to 6 post dose during 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.

  5. Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15 [ Time Frame: Pre-dose and up to 6 post dose during 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.


Secondary Outcome Measures :
  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) [ Time Frame: Up to 1 year post dose ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01349036


Locations
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United States, California
University California, Los Angeles
Los Angeles, California, United States, 90095
University California, San Francisco
San Francisco, California, United States, 94143
United States, Massachusetts
Dana Faber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
University of Texas, MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Plexxikon
Publications:
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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT01349036    
Other Study ID Numbers: PLX108-04
First Posted: May 6, 2011    Key Record Dates
Results First Posted: January 9, 2020
Last Update Posted: March 3, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Keywords provided by Daiichi Sankyo, Inc.:
Glioblastoma
brain cancer
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue