Immuno Positron Emission Tomography Study of GSK2849330 in Subjects With Human Epidermal Growth Factor Receptor 3-Positive Solid Tumors
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|ClinicalTrials.gov Identifier: NCT02345174|
Recruitment Status : Completed
First Posted : January 26, 2015
Last Update Posted : February 21, 2019
|Condition or disease||Intervention/treatment||Phase|
|Cancer Neoplasms||Drug: GSK2849330 Drug: 89Zr-GSK2849330||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open Label Positron Emission Tomography (PET) Imaging Study Using 89Zirconium to Investigate the Biodistribution of Anti-HER3 Monoclonal Antibody (mAb) GSK2849330 and Characterize Its Dose-receptor Occupancy Relationship in Subjects With Advanced HER3-Positive Solid Tumors|
|Actual Study Start Date :||March 19, 2015|
|Actual Primary Completion Date :||June 2, 2016|
|Actual Study Completion Date :||June 2, 2016|
Experimental: Imaging Phase + Continuation Phase
In Part 1 of the study, participants will receive a dose of 89Zr-GSK2849330 (Dose 1), with an activity of no more than 37 MegaBequerel (MBq) and a variable total dose of GSK2849330. PET scans will be acquired within 7 days. Two weeks after Dose 1 participants will receive second dose of 89Zr-GSK2849330 (Dose 2) and a variable total dose of GSK2849330. Participants will continue to receive unlabelled GSK2849330 (in Part 2) either at established dose level or as decided by medical monitor.
GSK2849330 solution (100 mg/mL) for infusion diluted in 0.9% sodium chloride to the appropriate concentration for the dose.
89Zr-GSK2849330 solution for intravenous administration diluted with GSK2849330 Solution for Infusion (unlabelled GSK2849330) with a target radioactivity of 37MBq and a total antibody concentration of 0.4 mg/mL or 1.2 mg/mL.
- Standardized Uptake Value (SUV). [ Time Frame: Up to Day 21 ]Regions of interest (RoI) will be outlined from PET-CT images to represent the tissue radioactivity concentration through the values of SUVmean and SUVpeak.
- Volume of region of interest. [ Time Frame: Up to Day 21 ]RoIs will be outlined to represent whole organs and include the volumes encircled
- Anatomical localization of radiolabel. [ Time Frame: Up to Day 21 ]Anatomical localization of radiolabel will be evaluated to establish dose-dependency of inhibition of target mediated uptake of 89Zr-GSK2849330 by unlabeled GSK2849330.
- Uptake of-GSK2849330 in tumors using pharmacometric model [ Time Frame: Up to Day 21 ]Uptake of GSK2849330 in tumors will be estimated to establish dose-dependency of inhibition of target mediated uptake of 89Zr-GSK2849330 by unlabeled GSK2849330.
- Change in uptake parameters in response to the dose difference between dose 1 and 2. [ Time Frame: Up to Day 21 ]Change in uptake parameters following dose 1 and 2 will estimated to establish dose-dependency of inhibition of target mediated uptake of 89Zr-GSK2849330 by unlabeled GSK2849330.
- Average radioactivity concentration in whole blood and plasma [ Time Frame: Up to Day 21 ]Average radioactivity concentration will be determined and expressed as SUV and is equal to tissue radioactivity concentration normalized by administered amount of radioactivity per body weight.
- Tumor features assessment [ Time Frame: Up to Day 21 ]Features of tumor will include central necrosis, irregular shape, non-uniform uptake and lesion ID
- Composite of pharmacokinetic (PK) parameters of GSK2849330 [ Time Frame: Predose, and at 1, 3, 6, 12 and 24 hours post dose. ]Measurements will include: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve (AUC(0-t), AUC(0-Tau) (repeat dosing) and/or AUC(0-Infinity) (single dose), apparent terminal phase elimination rate constant (lambda z) and apparent terminal phase half-life (t½)
- Organ dose measured in milliSievert (mSv) for each organ [ Time Frame: Up to Day 21 ]
- Effective dose value measured in mSv [ Time Frame: Up to Day 21 ]
- Overall incidence of Adverse events (AEs) and Serious Adverse events (SAEs) [ Time Frame: Average of 6 months ]AEs and SAEs will be collected from the time the first dose of study treatment is administered until 45 days following discontinuation of study treatment
- Change from baseline in laboratory parameters [ Time Frame: Baseline and up to 6 months ]Clinical laboratory tests will include clinical chemistry, routine urinalysis, haematology laboratory evaluations and additional parameters
- Left ventricular ejection fraction (LVEF) assessment [ Time Frame: Average of 6 months ]LVEF will be assessed as a measure of safety and tolerability measured by echocardiography (ECHO) or multi gated acquisition (MUGA) scans
- Vital signs monitoring. [ Time Frame: Average of 6 months ]Vital sign measurements will include systolic and diastolic blood pressure (BP), temperature, and pulse rate
- Serum titer of the anti-GSK2849330 antibodies. [ Time Frame: Average of 6 months ]Samples will be analyzed for the presence of anti-GSK2849330 antibodies using a validated immunoelectrochemiluminescent (ECL) assay.
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): NCT02345174
|GSK Investigational Site|
|Amsterdam, Netherlands, 1081 HV|
|GSK Investigational Site|
|Amsterdam, Netherlands, 1081 H|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)|