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Report for Clinical Trial NCT03463525

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

An Open-label PET Study to Determine Brain Exposure of Osimertinib After IV Microdose Administration of [11C]Osimertinib and Therapeutic Oral Doses of Osimertinib to Patients With EGFR Mutated NSCLC With Brain Metastases

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.

NCT03463525 Non-small Cell Lung Cancer
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

2 Interventions

Name: Osimertinib

Description: Osimertinib 80 mg once daily p.o. will be taken continuously by the patient from the day of the second PET exam.
Type: Drug
Group Labels: 3

[11C [11C] [11C]osimertinib + oral osimertinib

Name: [11C]osimertinib

Description: Patients will receive 3 single IV microdose administrations of [11C]osimertinib and PET exams on: Day 1, Day 2 (or up to Day 8) and Day 29.
Type: Drug
Group Labels: 3

[11C [11C] [11C]osimertinib + oral osimertinib


Primary Outcomes

Description: Measurement of the brain standard uptake value (SUV) seen on PET scan at baseline.

Measure: Brain Exposure to [11C]osimertinib in Tumour Region of Interest

Time: PET Scan on Day 1

Description: Pharmacokinetics of [11C]osimertinib by assessment of maximum plasma concentration (Cmax), derived from the curve taken at baseline.

Measure: Pharmacokinetics of [11C]osimertinib

Time: Blood samples collected on Day 1 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.

Description: Measurement of the brain to plasma partition coefficient (concentration brain/plasma ratio) by assessment of area under the concentration-time curve, derived from the curve taken at baseline.

Measure: Pharmacokinetics of [11C]osimertinib Brain to Plasma Ratio of Area Under the Concentration Curve (AUC)

Time: Measurement collected on Day 1 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.

Description: Pharmacokinetics of [11C]osimertinib radioactivity by assessment of time to Cmax (Tmax), derived from the curve taken at baseline.

Measure: Pharmacokinetics of [11C]osimertinib Radioactivity by Assessment of Time to Cmax (Tmax)

Time: Blood samples collected on Day 1 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.

Description: Measurement of the brain standard uptake value (SUV) seen on PET scan after a single dose of oral osimertinib.

Measure: Brain Exposure to [11C]osimertinib in Tumour Region of Interest

Time: PET Scan on Day 2

Description: Measurement of the brain standard uptake value (SUV) seen on PET scan after at least 21days of continuous oral osimertinib dosing.

Measure: Brain Exposure to [11C]osimertinib in Tumour Region of Interest

Time: PET Scan on Day 29

Description: Pharmacokinetics of [11C]osimertinib by assessment of maximum plasma concentration (Cmax), derived from the curve taken during the treatment period.

Measure: Pharmacokinetics of [11C]osimertinib

Time: Blood samples collected on Day 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.

Description: Pharmacokinetics of [11C]osimertinib by assessment of maximum plasma concentration (Cmax), derived from the curve taken during the treatment period.

Measure: Pharmacokinetics of [11C]osimertinib

Time: Blood samples collected on Day 29 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.

Description: Pharmacokinetics of [11C]osimertinib radioactivity by assessment of time to Cmax (Tmax), derived from the curve taken during the treatment period.

Measure: Pharmacokinetics of [11C]osimertinib Radioactivity by Assessment of Time to Cmax (Tmax)

Time: Blood samples collected on Day 2 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.

Description: Pharmacokinetics of [11C]osimertinib radioactivity by assessment of time to Cmax (Tmax), derived from the curve taken during the treatment period.

Measure: Pharmacokinetics of [11C]osimertinib Radioactivity by Assessment of Time to Cmax (Tmax)

Time: Blood samples collected on Day 29 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.

Description: Measurement of the brain to plasma partition coefficient (concentration brain/plasma ratio) by assessment of area under the concentration-time curve, derived from the curve taken during the treatment period.

Measure: Pharmacokinetics of [11C]osimertinib Brain to Plasma Ratio of Area Under the Concentration Curve (AUC)

Time: Measurement collected on Day 2 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.

Description: Measurement of the brain to plasma partition coefficient (concentration brain/plasma ratio) by assessment of area under the concentration-time curve, derived from the curve taken during the treatment period.

Measure: Pharmacokinetics of [11C]osimertinib Brain to Plasma Ratio of Area Under the Concentration Curve (AUC)

Time: Measurement collected on Day 29 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.

Secondary Outcomes

Description: Pharmacokinetics of osimertinib and its metabolite by assessment of AUC metabolite to parent ratio, derived from the curves taken during the treatment period.

Measure: Pharmacokinetics of Osimertinib and its Metabolite by Assessment of AUC Metabolite to Parent Ratio

Time: Blood samples collected on Day 2 at pre-administration, 2, 4 and 7.5 hour(s) post dose (can be modified if necessary).

Description: Pharmacokinetics of osimertinib by assessment of maximum plasma concentration (Cmax), derived from the curve taken during the treatment period.

Measure: Pharmacokinetics of Osimertinib by Assessment of Maximum Plasma Concentration (Cmax)

Time: Blood samples collected on Day 2 at pre-administration, 2, 4 and 7.5 hour(s) post dose (can be modified if necessary).

Description: Pharmacokinetics of osimertinib by assessment of area under the concentration-time curve from time zero to the last measurable time point.

Measure: Pharmacokinetics of Osimertinib by Assessment of Area Under the Concentration-time Curve

Time: Blood samples collected on Day 2 at pre-administration, 2, 4 and 7.5 hour(s) post dose (can be modified if necessary).

Description: Pharmacokinetics of osimertinib by assessment of time to Cmax (Tmax), derived from the curve taken during the treatment period.

Measure: Pharmacokinetics of Osimertinib by Assessment of Time to Cmax (Tmax)

Time: Blood samples collected on Day 2 at pre-administration, 2, 4 and 7.5 hour(s) post dose (can be modified if necessary).

Other Outcomes

Description: Collection and assessment of adverse events graded using CTCAE (version 4.03).

Measure: Incidence of Treatment Emergent Adverse Events [Safety and Tolerability] with IV [11C]osimertinib administration

Time: From study Day 1 and until 30 days after the study drug is discontinued.

Description: Collection and assessment of adverse events using CTCAE (version 4.03)

Measure: Incidence of Treatment Emergent Adverse Events [Safety and Tolerability] with continuous oral osimertinib

Time: From study Day 1 and until 30 days after the study drug is discontinued.

Purpose: Other

Allocation: N/A

Single Group Assignment


There are 3 SNPs

SNPs


1 L858R

4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR-TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) or T790M EGFR resistance mutation as assessed by local laboratory/or central laboratory via tissue/cytology or in plasma. --- L858R ---


2 L861Q

4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR-TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) or T790M EGFR resistance mutation as assessed by local laboratory/or central laboratory via tissue/cytology or in plasma. --- L858R --- --- L861Q ---


3 T790M

4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR-TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) or T790M EGFR resistance mutation as assessed by local laboratory/or central laboratory via tissue/cytology or in plasma. --- L858R --- --- L861Q --- --- T790M ---



HPO Nodes


HPO: