The purpose of this study is to establish the recommended phase 2 dose of eflornithine in combination with temozolomide in patients whose glioblastoma or astrocytoma is newly diagnosed, and to evaluate safety and tolerability of this combination at that dose.
This open label dose escalation and expansion study will be conducted using a standard dose-escalation design with escalating doses of eflornithine plus temozolomide at the approved dose level, followed by an expansion cohort that will further evaluate safety and preliminary efficacy of the combination at the recommended phase 2 dose. Duration of participation will be up to approximately 104 weeks in total per patient. Screening Period - A maximum screening duration of 4 weeks. Treatment Period - Up to approximately 104 weeks. Follow-Up Visit - 4 weeks from last treatment. Long-term Survival Follow-Up - up to 2 years from last treatment. A total of up to 66 patients will be enrolled in a non-randomized fashion (patients may be added to any of the dose levels below the RP2D to a maximum of approximately 20 per dose level with the intent of further characterizing safety and pharmacokinetics).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
66
Eflornithine 2.3 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
Eflornithine 1.75 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
Temozolomide 150 mg/m2 (with option to escalate per USPI maintenance phase instructions) administered orally once daily on a 5 days on, 23 days off schedule
University of Alabama at Birmingham
Birmingham, Alabama, United States
WITHDRAWNHenry Ford Hospital
Detroit, Michigan, United States
RECRUITINGColumbia University Medical Center - Herbert Irving Pavilion
New York, New York, United States
RECRUITINGDuke University
Durham, North Carolina, United States
RECRUITINGThe Cleveland Clinic
Cleveland, Ohio, United States
RECRUITINGBrown University Health/Rhode Island Hospital
Providence, Rhode Island, United States
RECRUITINGUT MD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGUniversity of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, United States
RECRUITINGAssessment of Dose Limiting Toxicities
Protocol Defined Dose Limiting Toxicities
Time frame: 8 weeks
Incidence of TEAEs All Grades
All Grades
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Incidence of TEAEs Grade 3+
Grade 3+
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Incidence of TEAEs Serious
Serious
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Incidence of TEAEs Leading to Discontinuation
Leading to Discontinuation
Time frame: From enrollment to the end of treatment
Vital Signs (Heart and Respiratory Rate)
Change from Baseline in Heart Rate and Respiratory Rate
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Vital Signs (Blood Pressure)
Change from Baseline in Systolic Blood Pressure and Diastolic Blood Pressure
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Incidence of Treatment-Emergent Abnormalities in Clinical Laboratory Tests
Lab abnormalities by CTCAE v5.0 Grade
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Overall Survival
Until death or initiation of new anticancer therapy
Time frame: From enrollment to up to 2 years after last dose
Progression Free Survival
Per RANO Criteria as assessed by MRI
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Overall Response Rate
Per RANO Criteria as assessed by MRI
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Pharmacokinetics Cmax
observed maximum concentration
Time frame: Baseline to Steady State (2 weeks)
Pharmacokinetics Cmin
observed minimum concentration
Time frame: Baseline to Steady State (2 weeks)
Pharmacokinetics Tmax
time of observed maximum concentration
Time frame: Baseline to Steady State (2 weeks)
Pharmacokinetics AUCt
area under the concentration-time curve
Time frame: Baseline to Steady State (2 weeks)
Pharmacokinetics lambdaz
elimination rate constant
Time frame: Baseline to Steady State (2 weeks)
Pharmacokinetics t 1/2
elimination half life
Time frame: Baseline to Steady State (2 weeks)
QTcF-Concentration Relationship
Assessment of change in QTcF relative to plasma concentration of eflornithine
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Time frame: Baseline to Steady State (2 weeks)
Assessment of QTcF
Change from baseline in QTcF
Time frame: Baseline to Steady State (2 weeks)