Clinical trial NCT01349036: A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma
Official title: A Phase 2 Study of Orally Administered PLX3397 in Patients With Recurrent Glioblastoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Recurrent Glioblastoma
Keywords: Glioblastoma
brain cancer
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Plexxikon
First posted: 2011-05-06
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Summary of Response Rates in Participants on Treatment With PLX3397
timeFrame: 6 months post dose
measure: Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15
timeFrame: Pre-dose and up to 6 post dose during cycle 1, Day 15
measure: Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15
timeFrame: Pre-dose and up to 6 post dose during cycle 1, Day 15
measure: Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15
timeFrame: Pre-dose and up to 6 post dose during cycle 1, Day 15
measure: Mean Plasma Pharmacokinetic Parameters of PLX3397 After Oral Administration of 1000 mg/Day - Cycle 1 Day 15
timeFrame: Pre-dose and up to 6 post dose during cycle 1, Day 15
Secondary outcomes:
measure: 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)
timeFrame: Up to 1 year post dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University California, Los Angeles
state: California
city: San Francisco
country: United States
facility: University California, San Francisco
state: California
city: Boston
country: United States
facility: Dana Faber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: University of Texas, MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute University of Utah
state: Utah
Study officials:
References:
citation: 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.