18F-FDG PET and Osimertinib in Evaluating Glucose Utilization in Patients with EGFR Activated Recurrent Glioblastoma

NCT03732352 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 18-001000NCI-2018-02010
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET) and osimertinib works in evaluating glucose utilization in patients with EGFR activated glioblastoma. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 18F-FDG PET imaging may help to detect changes in tumor glucose utilization, which may allow investigators to obtain an early read out on the impact of osimertinib on recurrent glioblastoma patients whose tumors have EGFR activation.

Conditions

EGFR Gene Amplification; EGFR Gene Mutation; Glioblastoma; Recurrent Glioblastoma; Supratentorial Glioblastoma; TP53 Wt Allele

Outcome Measures

Primary Outcomes (2)

• Intrapatient variance of tumor fludeoxyglucose F-18 (FDG) uptake as determined by a double baseline FDG positron emission tomography (PET) prior to osimertinib exposure

  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.

  At baseline

• Change in FDG uptake in tumor after short course exposure to osimertinib

  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.

  Baseline to day -1

Secondary Outcomes (4)

• Incidence and severity of adverse events (AEs) assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03

  Up to 2 years

• 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

  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

• Correlation between the reduction in glucose uptake and 6 months PFS

  Up to 2 years

• Concentrations of osimertinib and metabolites AZ5104 and AZ7550 in post-dosing plasma samples.

  At the end of Cycle 1 (each cycle is 28 days).

Study Arms (1)

Treatment (18F-FDG PET, osimertinib)

EXPERIMENTAL

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; Drug: Osimertinib; Procedure: Positron Emission Tomography

Interventions

Fludeoxyglucose F-18 OTHER

Given IV

Also known as: 18FDG, FDG, fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18

Treatment (18F-FDG PET, osimertinib)

Osimertinib DRUG

Given PO

Also known as: AZD-9291, AZD9291, Mereletinib, Tagrisso

Treatment (18F-FDG PET, osimertinib)

Positron Emission Tomography PROCEDURE

Undergo fludeoxyglucose F-18 PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Treatment (18F-FDG PET, osimertinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be able to provide written informed consent
• Patients must have histologically proven World Health Organization (WHO) grade IV glioblastoma who have supratentorial contrast enhancing progressive or recurrent tumor by MRI imaging following standard or experimental treatment.
• Patients must have measurable contrast enhancing disease with a measurement of at least 1 x 1 x 1 cm using MRI contrast imaging
• Patients must have recovered from severe toxicity of prior therapy. The following intervals from previous treatments are required to be eligible:
• weeks from the completion of radiation
• weeks from a nitrosourea chemotherapy
• weeks from a non-nitrosourea chemotherapy
• weeks from any Food and Drug Administration (FDA) approved agents
• half-lives or 4 weeks, whichever is greater, from any investigational (not FDA-approved) agents
• weeks from the last treatment with bevacizumab
• weeks from administration of a non-cytotoxic, FDA-approved agent other than bevacizumab (e.g., hydroxychloroquine, etc.)
• Patient tumor sample must have evidence of EGFR activation as determined by EGFR amplification and/or EGFR mutations by fluorescent in situ hybridization (FISH) or sequencing approaches
• Patient tumor sample must not have p53 mutation
• Note: Patients will be enrolled based on the documented EGFR/p53 status from the previous assays completed locally. If post enrollment evaluation of the archival tissue revealed that neither EGFR amplification nor EGFR mutations were present by using FISH or next generation sequencing, or mutant p53 by exon sequencing, the patients may continue their participation in the study. The investigator should discuss with patients regarding their willingness of continuation of participation in the study
• Patients must have a Karnofsky performance status (KPS) \>= 60

You may not qualify if:

• Involvement in the planning and/or conduct of the study
• Previous enrollment in the present study or previous treatment with osimertinib
• Prior exposure to EGFR targeted therapy
• Currently receiving any other investigational agents
• Currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks prior)
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the exception of alopecia and grade 2, prior platinum-therapy? related neuropathy
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator?s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \> 470 msec obtained from an electrocardiogram (ECG), using the screening clinic ECG machine derived QTc value
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
• Absolute neutrophil count \< 1.5 x 10\^9/L
• Platelet count \< 100 x 10\^9/L
• Hemoglobin \< 90 g/L

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Fluorodeoxyglucose F18; osimertinib; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Deoxyglucose; Deoxy Sugars; Carbohydrates; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Timothy Cloughesy

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: November 6, 2018
• Study Start: November 28, 2018
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Locations

US (1)