18F-FDG PET and Osimertinib in Evaluating Glucose Utilization in Patients With EGFR Activated Recurrent Glioblastoma
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|ClinicalTrials.gov Identifier: NCT03732352|
Recruitment Status : Recruiting
First Posted : November 6, 2018
Last Update Posted : November 12, 2019
|Condition or disease||Intervention/treatment||Phase|
|EGFR Gene Amplification EGFR Gene Mutation Glioblastoma Recurrent Glioblastoma Supratentorial Glioblastoma TP53 wt Allele||Other: Fludeoxyglucose F-18 Drug: Osimertinib Procedure: Positron Emission Tomography||Phase 2|
I. Define the test - retest variance of tumor fludeoxyglucose (FDG) uptake using double baseline 18F-FDG PET imaging (18 to 54 hours apart) in patients with EGFR activated recurrent glioblastoma.
II. After defining #1, evaluate whether osimertinib can create a statistically significant decrease in glucose utilization as determined using early, post dosing (24-72 hour) FDG-PET imaging in patients with EGFR activated recurrent glioblastoma.
I. Safety and tolerability of osimertinib in this patient population. II. Determine clinical effect of osimertinib in this patient population, as determined by 6 months progression-free survival.
III. Correlated clinical effect of osimertinib with FDG-PET results in this patient population, to define by receiver operating characteristic (ROC) analysis a clinically meaningful decrease in glucose utilization, which correlates with the clinical effect.
IV. Evaluate pharmacokinetic (PK) in this patient population using spot PK during imaging and at set time points during the study.
Within days -28 to -4, patients receive fludeoxyglucose F-18 intravenously (IV) and after 60 minutes undergo PET scan over 15 minutes. After 18-54 hours, patients undergo a second fludeoxyglucose F-18 PET scan. Patients then receive osimertinib orally (PO) once daily (QD) on days -3 to -1 and after 24-72 hours, undergo a third fludeoxyglucose F-18 PET scan. Patients then receive osimertinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 2 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Creating Metabolic Vulnerabilities in Patients With EGFR Activated Recurrent Glioblastoma by Inhibiting EGFR With Osimertinib|
|Actual Study Start Date :||November 28, 2018|
|Estimated Primary Completion Date :||November 1, 2020|
|Estimated Study Completion Date :||November 1, 2021|
Experimental: Treatment (18F-FDG PET, osimertinib)
Within days -28 to -4, patients receive fludeoxyglucose F-18 IV and after 60 minutes undergo PET scan over 15 minutes. After 18-54 hours, patients undergo a second fludeoxyglucose F-18 PET scan. Patients then receive osimertinib PO QD on days -3 to -1 and after 24-72 hours, undergo a third fludeoxyglucose F-18 PET scan. Patients then receive osimertinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Fludeoxyglucose F-18
Procedure: Positron Emission Tomography
Undergo fludeoxyglucose F-18 PET scan
- Intrapatient variance of tumor fludeoxyglucose F-18 (FDG) uptake as determined by a double baseline FDG positron emission tomography (PET) prior to osimertinib exposure [ Time Frame: At baseline ]Test-retest variances in FDG uptake will be estimated considering the variance of sample specific differences between first and second PET scans. This variance component will be estimated using a Bayesian conjugate analysis of Gaussian variates. Model adequacy diagnostics will compare predictive distributions to the observed data via posterior predictive assessment. Bayesian (95%) high posterior density intervals, and Bayesian posterior means will be used as the basis for statistical inference.
- Change in FDG uptake in tumor after short course exposure to osimertinib [ Time Frame: Baseline to day -1 ]In order to estimate the difference in FDG tumor uptake between pre and post exposure to osimertinib, a simple change model will be considered, comparing the mean baseline uptake with the mean uptake, after treatment. A formal test for difference in mean will be based on a paired T statistic for difference in mean. 95% confidence intervals will be used to quantify uncertainty in estimation.
- Incidence and severity of adverse events (AEs) assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 2 years ]All events will be recorded from the time a subject has signed the Informed Consent Form. AE analyses will include only treatment emergent adverse events. Specifically, following quantities will be estimated: incidence (number [no.] of patients) and frequency (no. of events) overall and broken down by System Organ Classification and incidence (no. of patients) and frequency (no. of events) broken down by severity.
- Percentage of participants surviving 6 months from the start of study treatment without progression of disease determined by progression free survival (PFS) according to Response Assessment in Neuro-oncology criteria [ Time Frame: From the date of study treatment initiation to the date of the first documented progression or to death due to any cause, assessed up to 6 months ]Will be based on the sampling distribution of a simple binomial proportion. Additionally, descriptive data will be provided for the duration of PFS as a Kaplan-Meier curve.
- Correlation between the reduction in glucose uptake and 6 months PFS [ Time Frame: Up to 2 years ]Reduction in glucose uptake will be correlated with clinical outcome-- 6 months PFS, receiver operating characteristic curve (ROC) analyses of simple thresholding strategies will be performed using leave one out cross validation.
- Concentrations of osimertinib and metabolites AZ5104 and AZ7550 in post-dosing plasma samples. [ Time Frame: At the end of Cycle 1 (each cycle is 28 days). ]PK concentration data will be summarized using appropriate summary statistics
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): NCT03732352
|United States, California|
|UCLA / Jonsson Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90095|
|Contact: Timothy F. Cloughesy 310-825-5321 firstname.lastname@example.org|
|Principal Investigator: Timothy F. Cloughesy|
|Principal Investigator:||Timothy Cloughesy||UCLA / Jonsson Comprehensive Cancer Center|