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TerminatedNCT01349036Updated Mar 3, 2020Results posted

A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma

A Phase 2 interventional study of PLX3397 in Recurrent Glioblastoma, sponsored by Daiichi Sankyo. Terminated at 6 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-03-03.

Sponsored by Daiichi Sankyo · Phase 2, Interventional, and Treatment

Why this study was terminated
Business Decision
Phase
Phase 2
Study type
Interventional
Enrollment
38
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

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

02

Conditions studied

  • Recurrent Glioblastoma

Keywords

  • Glioblastoma
  • brain cancer
03

In context

Glioblastoma

1,920 studies on the registry are indexed under Glioblastoma; 450 are open to participants now.

This study's enrollment of 38 is close to the median of 36 across 1,618 interventional studies indexed under Glioblastoma.

Browse Glioblastoma studies →

Lead sponsor

Daiichi Sankyo is the lead sponsor of 316 studies on the registry; 35 are open to participants now.

Of its 51 completed or terminated interventional studies of FDA-regulated products, 38 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
38 participants (actual)

Study arms

  • 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

  • Experimental
    PLX3397-Cohort 2

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

    Drug: PLX3397

Interventions

  • DrugPLX3397

    Capsules administered once or twice daily, continuous dosing

    Also known as: Pexidartinib

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 6 months post dose

  2. 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.

    Time frame: Pre-dose and up to 6 post dose during cycle 1, Day 15

  3. 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.

    Time frame: Pre-dose and up to 6 post dose during cycle 1, Day 15

  4. 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.

    Time frame: Pre-dose and up to 6 post dose during cycle 1, Day 15

  5. 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.

    Time frame: 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)

    Time frame: Up to 1 year post dose

07

Results

Posted Jan 9, 2020
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.

Participant flow

A total of 38 participants who met all inclusion and none of the exclusion criteria were enrolled and received the study drug.

Participant flow — Overall Study
MilestonePLX3397 - Cohort 1 (Surgical)PLX3397 - Cohort 2 (Non-surgical)
Started1424
Completed00
Not completed1424
Withdrew: Disease progression1322
Withdrew: Other10
Withdrew: Withdrawal by subject02

Outcome measures

PrimarySummary 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.

Time frame:
6 months post dose
Reported as:
Count of participants · Participants
Summary of Response Rates in Participants on Treatment With PLX3397
ParticipantsSurgical Cohort 1 (N=14)Non-Surgical Cohort 2 (N=24)
Six-month PFS rate12
Overall survival1021
Complete response rate00
Partial response rate00
Stable disease rate34
Progressive disease rate1018
Not Evaluable12
PrimaryMean 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.

Time frame:
Pre-dose and up to 6 post dose during cycle 1, Day 15
Reported as:
Mean · hours
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15
hoursPLX3397 - Cohort 1 (Surgical)PLX3397 - Cohort 2 (Non-surgical)
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 152.09 ± 1.041.71 ± 0.90
PrimaryMean 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.

Time frame:
Pre-dose and up to 6 post dose during cycle 1, Day 15
Reported as:
Mean · ng/mL
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15
ng/mLPLX3397 - Cohort 1 (Surgical)PLX3397 - Cohort 2 (Non-surgical)
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 157760 ± 23308030 ± 2790
PrimaryMean 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.

Time frame:
Pre-dose and up to 6 post dose during cycle 1, Day 15
Reported as:
Mean · hr*ng/mL
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15
hr*ng/mLPLX3397 - Cohort 1 (Surgical)PLX3397 - Cohort 2 (Non-surgical)
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 1524900 ± 670026100 ± 9260
PrimaryMean 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.

Time frame:
Pre-dose and up to 6 post dose during cycle 1, Day 15
Reported as:
Mean · hr*ng/mL
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15
hr*ng/mLPLX3397 - Cohort 1 (Surgical)PLX3397 - Cohort 2 (Non-surgical)
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 1536100 ± 1000036900 ± 12200
SecondaryIncidence (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
Reported as:
Count of participants · Participants
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)
ParticipantsPLX3397 - Cohort 1 (Surgical)PLX3397 - Cohort 2 (Non-surgical)
Any Event1222
Fatigue614
Constipation31
Nausea13
Hair color changes24
Aspartate aminotransferase increased33
Alanine aminotransferase increased23
Decreased appetite33
Headache13
Pyrexia21
Dry Mouth20
Rash21
Neutropenia03
Lymphopenia20
Blood Lactate Dehydrogenase Increased21
Hypertension20

Adverse events

Collected over Adverse event data were collected from after the first dose to 28 days after the last dose.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
PLX3397 - Cohort 1 (Surgical)0/14 (0%)8/14 (57.1%)14/14 (100%)
PLX3397 - Cohort 2 (Non-surgical)1/24 (4.2%)11/24 (45.8%)22/24 (91.7%)
Most frequent serious events
Showing 10 of 22
Most frequent serious events
EventPLX3397 - Cohort 1 (Surgical)PLX3397 - Cohort 2 (Non-surgical)
ConvulsionNervous system disorders3/145/24
PneumoniaInfections and infestations2/140/24
DysarthriaNervous system disorders1/140/24
MeningitisInfections and infestations1/140/24
HypertensionVascular disorders1/140/24
ThrombosisVascular disorders1/140/24
NauseaGastrointestinal disorders1/140/24
VomitingGastrointestinal disorders1/140/24
Oedema peripheralGeneral disorders1/140/24
Muscular weaknessMusculoskeletal and connective tissue disorders1/140/24
Most frequent other events
Showing 10 of 117
Most frequent other events
EventPLX3397 - Cohort 1 (Surgical)PLX3397 - Cohort 2 (Non-surgical)
FatigueGeneral disorders7/1414/24
HeadacheNervous system disorders6/148/24
NauseaGastrointestinal disorders6/143/24
Decreased appetiteMetabolism and nutrition disorders6/143/24
DizzinessNervous system disorders5/142/24
PyrexiaGeneral disorders5/142/24
ConstipationGastrointestinal disorders5/141/24
ConvulsionNervous system disorders4/144/24
HypertensionVascular disorders4/146/24
AphasiaNervous system disorders3/141/24

Baseline characteristics

Age, Continuous
Age, Continuous(years)PLX3397 - Cohort 1 (Surgical)PLX3397 - Cohort 2 (Non-surgical)Total
Mean56.1 ± 8.654.1 ± 11.754.8 ± 10.6
Sex: Female, Male
Sex: Female, Male(Participants)PLX3397 - Cohort 1 (Surgical)PLX3397 - Cohort 2 (Non-surgical)Total
Female6713
Male81725
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PLX3397 - Cohort 1 (Surgical)PLX3397 - Cohort 2 (Non-surgical)Total
American Indian or Alaska Native000
Asian011
Native Hawaiian or Other Pacific Islander000
Black or African American011
White142135
More than one race011
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)PLX3397 - Cohort 1 (Surgical)PLX3397 - Cohort 2 (Non-surgical)Total
United States142438
08

Study locations

6 sites
  • University California, Los Angeles
    Los Angeles, California 90095, United States
  • University California, San Francisco
    San Francisco, California 94143, United States
  • Dana Faber Cancer Institute
    Boston, Massachusetts 02115, United States
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10065, United States
  • University of Texas, MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • Huntsman Cancer Institute University of Utah
    Salt Lake City, Utah 84132, United States
09

References and documents

Publications

  • 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. PubMed 18356283 ↗

Individual participant data

Plan to share: Yes — 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 information: Study protocol, Sap, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 3, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01349036
Lead sponsor
Daiichi Sankyo
Collaborators
Plexxikon
Responsible party
Sponsor
First posted
May 6, 2011
Start date
Dec 3, 2011
Primary completion
Nov 5, 2013
Completion
Nov 5, 2013
Results posted
Jan 9, 2020
Last update
Mar 3, 2020

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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