Open-label PET Study With [11C]Osimertinib in Patients With EGFRm NSCLC and Brain Metastases

Phase 1

Completed

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: Osimertinib; Drug: [11C]osimertinib

• Registration Number: NCT03463525
• Lead Sponsor: AstraZeneca

Brief Summary

This is an open-label, single centre, Phase I study to determine the brain exposure of \[11C\]osimertinib in patients with EGFRm NSCLC with brain metastases.

Detailed Description

A Single-centre, Open-label, PET imaging and Pharmacokinetic Study of IV Administered \[11C\]osimertinib in EGFRm Non-small cell lung cancer patients with brain metastases. The study will consist of 2 phases, an imaging phase and a continuous access phase.

Study Timeline

• Study First Submitted: 2018-02-20
• Study First Submitted QC: 2018-03-12
• Study First Posted: 2018-03-13
• Study Start: 2018-10-24
• Primary Completion: 2020-03-19
• Study Completion: 2020-10-05
• Status Verified: 2022-04
• Results First Submitted: 2022-04-25
• Results First Submitted QC: 2022-04-25
• Last Update Submitted: 2022-04-25
• Results First Posted: 2023-01-27
• Last Update Posted: 2023-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[11C]osimertinib + oral osimertinib	Osimertinib	IV microdose administrations of \[11C\]osimertinib co-administered with 80 mg daily oral osimertinib.
[11C]osimertinib + oral osimertinib	[11C]osimertinib	IV microdose administrations of \[11C\]osimertinib co-administered with 80 mg daily oral osimertinib.

Primary Outcome Measures

Name	Time	Method
Maximum Concentration of Percent of Injected Dose in the Whole Brain (Cmax, %ID Brain) of [11C]Osimertinib	Day 1, Day 2 (or up to Day 8) and Day 25	During the PET examination time, a series of arterial blood samples were taken to measure Cmax, %ID brain of \[11C\]osimertinib.
Time of Maximum Radioactivity Concentration in the Brain (Tmax, Brain) of [11C]Osimertinib	Day 1, Day 2 (or up to Day 8) and Day 25	The Tmax, brain was determined directly from the observed concentration versus time data.
Maximum Concentration of Brain Standardized Uptake Value (Cmax, SUV Brain) of [11C]Osimertinib	Day 1, Day 2 (or up to Day 8) and Day 25	During the PET examination time, a series of arterial blood samples were taken to measure Cmax, SUV brain of \[11C\]osimertinib.
Brain to Plasma Partition Coefficient (Kp) of [11C]Osimertinib	Day 1, Day 2 (or up to Day 8) and Day 25	The Kp was defined as ratio of radiolabeled drug in brain to that in plasma calculated as area under the brain radioactivity concentration-time curve between 0 and 90 minutes/area under the plasma radioactivity concentration-time curve between 0 and 90 minutes.

Secondary Outcome Measures

Name	Time	Method
Maximum Concentration at Steady State (Css,Max) of Osimertinib and Metabolite AZ5104	Pre-dose and 2, 4 and 7.5 hours postdose on Day 25	Venous blood samples were collected to determine Css,max of osimertinib and metabolite AZ5104.
Area Under the Concentration-Time Curve at Steady State (AUCss) of Osimertinib and Metabolite AZ5104	Pre-dose and 2, 4 and 7.5 hours postdose on Day 25	Venous blood samples were collected to determine AUCss of osimertinib and metabolite AZ5104.
Time of Maximum Drug Concentration at Steady State (Tss,Max) of Osimertinib and Metabolite AZ5104	Pre-dose and 2, 4 and 7.5 hours postdose on Day 25	Venous blood samples were collected to determine tss,max of osimertinib and metabolite AZ5104.
Metabolite to Parent Ratio of AUCss	Pre-dose and 2, 4 and 7.5 hours postdose on Day 25	Venous blood samples were collected to determine AUCss of osimertinib and metabolite AZ5104.
Metabolite to Parent Ratio of Css,Max	Pre-dose and 2, 4 and 7.5 hours postdose on Day 25	Venous blood samples were collected to determine Css,max of osimertinib and metabolite AZ5104.

Trial Locations

Locations (1)

Research Site; 🇸🇪 Stockholm, Sweden