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NCT01349036

A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma

Terminated Phase 2 Results posted Last updated 3 March 2020
What this trial tests

Phase 2 trial testing PLX3397 in Recurrent Glioblastoma in 38 participants. Terminated before completion.

Timeline
3 December 2011
Primary endpoint
5 November 2013
5 November 2013

Quick facts

Lead sponsorDaiichi Sankyo
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment38
Start date3 December 2011
Primary completion5 November 2013
Estimated completion5 November 2013
Sites6 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Daiichi Sankyo — full company profile →

Who can join

18 and older, any sex, with Recurrent Glioblastoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Summary of Response Rates in Participants on Treatment With PLX3397 Primary · 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 unti

Six-month PFS rate
GroupValue95% CI
Surgical Cohort 1 (N=14)1
Non-Surgical Cohort 2 (N=24)2
Overall survival
GroupValue95% CI
Surgical Cohort 1 (N=14)10
Non-Surgical Cohort 2 (N=24)21
Complete response rate
GroupValue95% CI
Surgical Cohort 1 (N=14)0
Non-Surgical Cohort 2 (N=24)0
Partial response rate
GroupValue95% CI
Surgical Cohort 1 (N=14)0
Non-Surgical Cohort 2 (N=24)0
Stable disease rate
GroupValue95% CI
Surgical Cohort 1 (N=14)3
Non-Surgical Cohort 2 (N=24)4
Progressive disease rate
GroupValue95% CI
Surgical Cohort 1 (N=14)10
Non-Surgical Cohort 2 (N=24)18
Not Evaluable
GroupValue95% CI
Surgical Cohort 1 (N=14)1
Non-Surgical Cohort 2 (N=24)2
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15 Primary · 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.

GroupValue95% CI
PLX3397 - Cohort 1 (Surgical)2.09± 1.04
PLX3397 - Cohort 2 (Non-surgical)1.71± 0.90
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15 Primary · 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.

GroupValue95% CI
PLX3397 - Cohort 1 (Surgical)7760± 2330
PLX3397 - Cohort 2 (Non-surgical)8030± 2790
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15 Primary · 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.

GroupValue95% CI
PLX3397 - Cohort 1 (Surgical)24900± 6700
PLX3397 - Cohort 2 (Non-surgical)26100± 9260
Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15 Primary · 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.

GroupValue95% CI
PLX3397 - Cohort 1 (Surgical)36100± 10000
PLX3397 - Cohort 2 (Non-surgical)36900± 12200
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) Secondary · Up to 1 year post dose
Any Event
GroupValue95% CI
PLX3397 - Cohort 1 (Surgical)12
PLX3397 - Cohort 2 (Non-surgical)22
Fatigue
GroupValue95% CI
PLX3397 - Cohort 1 (Surgical)6
PLX3397 - Cohort 2 (Non-surgical)14
Constipation
GroupValue95% CI
PLX3397 - Cohort 1 (Surgical)3
PLX3397 - Cohort 2 (Non-surgical)1
Nausea
GroupValue95% CI
PLX3397 - Cohort 1 (Surgical)1
PLX3397 - Cohort 2 (Non-surgical)3
Hair color changes
GroupValue95% CI
PLX3397 - Cohort 1 (Surgical)2
PLX3397 - Cohort 2 (Non-surgical)4
Aspartate aminotransferase increased
GroupValue95% CI
PLX3397 - Cohort 1 (Surgical)3
PLX3397 - Cohort 2 (Non-surgical)3
Alanine aminotransferase increased
GroupValue95% CI
PLX3397 - Cohort 1 (Surgical)2
PLX3397 - Cohort 2 (Non-surgical)3
Decreased appetite
GroupValue95% CI
PLX3397 - Cohort 1 (Surgical)3
PLX3397 - Cohort 2 (Non-surgical)3

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data were collected from after the first dose to 28 days after the last dose.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PLX3397 - Cohort 1 (Surgical)
Serious: 8/14 (57%)
Deaths: 0/14
PLX3397 - Cohort 2 (Non-surgical)
Serious: 11/24 (46%)
Deaths: 1/24

Serious adverse events (22 terms)

ReactionSystemPLX3397 - Cohort 1 (Surgic…PLX3397 - Cohort 2 (Non-su…
ConvulsionNervous system disorders
PneumoniaInfections and infestations
Cerebrovascular accidentNervous system disorders
DysarthriaNervous system disorders
HeadacheNervous system disorders
HydrocephalusNervous system disorders
MeningitisInfections and infestations
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
ALT increasedInvestigations
AST increasedInvestigations
INR increasedInvestigations
WBC count decreasedInvestigations
HypertensionVascular disorders
ThrombosisVascular disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
DehydrationMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (117 terms — click to expand)

ReactionSystemPLX3397 - Cohort 1 (Surgic…PLX3397 - Cohort 2 (Non-su…
FatigueGeneral disorders
HeadacheNervous system disorders
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
HypertensionVascular disorders
DizzinessNervous system disorders
PyrexiaGeneral disorders
ConstipationGastrointestinal disorders
ConvulsionNervous system disorders
Hair colour changesSkin and subcutaneous tissue disorders
HemiparesisNervous system disorders
AphasiaNervous system disorders
DiarrhoeaGastrointestinal disorders
Dry mouthGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
Aspartate aminotransferase increasedInvestigations
Alanine aminotransferase increasedInvestigations
Urinary incontinenceRenal and urinary disorders
Memory impairmentNervous system disorders
AmnesiaNervous system disorders
HemianopiaNervous system disorders
Psychomotor skills impairedNervous system disorders
AtaxiaNervous system disorders
DysgeusiaNervous system disorders
TremorNervous system disorders
Gait disturbanceGeneral disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
HyponatraemiaMetabolism and nutrition disorders
HypocalcaemiaMetabolism and nutrition disorders
RashSkin and subcutaneous tissue disorders
Skin hypopigmentationSkin and subcutaneous tissue disorders
Dry skinSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
Periorbital oedemaEye disorders
Lacrimation increasedEye disorders
Confusional statePsychiatric disorders
AnxietyPsychiatric disorders
InsomniaPsychiatric disorders

Most-reported serious reactions: Convulsion, Pneumonia, Cerebrovascular accident, Dysarthria, Headache, Hydrocephalus, Meningitis, Anaemia.

Data from ClinicalTrials.gov NCT01349036 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tumor microenvironment as a therapeutic target in cancer.
    Xiao Y, Yu D. · · 2021 · cited 1438× · PMID 33259885 · DOI 10.1016/j.pharmthera.2020.107753
  2. Macrophages and therapeutic resistance in cancer.
    Ruffell B, Coussens LM. · · 2015 · cited 1235× · PMID 25858805 · DOI 10.1016/j.ccell.2015.02.015
  3. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy.
    Cannarile MA, Weisser M, Jacob W, Jegg AM, et al · · 2017 · cited 796× · PMID 28716061 · DOI 10.1186/s40425-017-0257-y
  4. Tumor-associated macrophages: from basic research to clinical application.
    Yang L, Zhang Y. · · 2017 · cited 654× · PMID 28241846 · DOI 10.1186/s13045-017-0430-2
  5. Brain immunology and immunotherapy in brain tumours.
    Sampson JH, Gunn MD, Fecci PE, Ashley DM. · · 2020 · cited 525× · PMID 31806885 · DOI 10.1038/s41568-019-0224-7
  6. New horizons in tumor microenvironment biology: challenges and opportunities.
    Chen F, Zhuang X, Lin L, Yu P, et al · · 2015 · cited 521× · PMID 25857315 · DOI 10.1186/s12916-015-0278-7
  7. Glioma targeted therapy: insight into future of molecular approaches.
    Yang K, Wu Z, Zhang H, Zhang N, et al · · 2022 · cited 518× · PMID 35135556 · DOI 10.1186/s12943-022-01513-z
  8. Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study.
    Butowski N, Colman H, De Groot JF, Omuro AM, et al · · 2016 · cited 469× · PMID 26449250 · DOI 10.1093/neuonc/nov245

Verify or expand the search:

Other trials of PLX3397

Trials testing the same drug.

Other recruiting trials for Recurrent Glioblastoma

Currently open trials in the same condition.

Other Daiichi Sankyo trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01349036.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing