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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
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE January 19, 2015
First Posted Date  ICMJE January 26, 2015
Last Update Posted Date February 21, 2019
Actual Study Start Date  ICMJE March 19, 2015
Actual Primary Completion Date June 2, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 19, 2015)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02345174 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2015)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Immuno Positron Emission Tomography Study of GSK2849330 in Subjects With Human Epidermal Growth Factor Receptor 3-Positive Solid Tumors
Official Title  ICMJE 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
Brief Summary Human epidermal growth factor receptor 3 (HER3) expression is seen across a wide variety of solid malignancies and is associated with poor prognosis. Up-regulation of HER3 expression and activity is also associated with resistance to multiple pathway inhibitors. GSK2849330, a monoclonal antibody (mAb) targeting HER3, is a new agent for subjects whose tumors express HER3. This study aims to characterise the biodistribution and dose-receptor occupancy relationship of GSK2849330 in patients with advanced HER3 expressing solid tumours via the use of PET imaging. This study will be conducted in two parts. Part 1 will be the imaging phase where each subject will receive two doses of GSK2849330 containing both Zirconium-89 (89Zr) labelled GSK2849330 and unlabeled GSK2849330. The amount of unlabeled GSK2849330 present in each dose will be varied to explore the effect on target mediated uptake of 89Zr into HER3 expressing tissues and tumors. Subjects will then proceed to the continuation phase (Part 2) for continued treatment with unlabelled GSK2849330. The study is planned to enroll approximately 12-15 subjects.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE
  • Cancer
  • Neoplasms
Intervention  ICMJE
  • Drug: GSK2849330
    GSK2849330 solution (100 mg/mL) for infusion diluted in 0.9% sodium chloride to the appropriate concentration for the dose.
  • Drug: 89Zr-GSK2849330
    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.
Study Arms  ICMJE 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.
Interventions:
  • Drug: GSK2849330
  • Drug: 89Zr-GSK2849330
Publications * Menke-van der Houven van Oordt CW, McGeoch A, Bergstrom M, McSherry I, Smith DA, Cleveland M, Al-Azzam W, Chen L, Verheul H, Hoekstra OS, Vugts DJ, Freedman I, Huisman M, Matheny C, van Dongen G, Zhang S. Immuno-PET Imaging to Assess Target Engagement: Experience from (89)Zr-Anti-HER3 mAb (GSK2849330) in Patients with Solid Tumors. J Nucl Med. 2019 Jul;60(7):902-909. doi: 10.2967/jnumed.118.214726. Epub 2019 Feb 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 16, 2016)
6
Original Estimated Enrollment  ICMJE
 (submitted: January 19, 2015)
15
Actual Study Completion Date  ICMJE June 2, 2016
Actual Primary Completion Date June 2, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Males and females >=18 years of age (at the time consent is obtained).
  • Written informed consent provided.
  • Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
  • Sufficient archival tumor specimen is available for HER3 immunohistochemistry (IHC) analysis, or subject is willing to undergo a tumor biopsy for HER3 IHC analysis.
  • Subjects must have tumours with documented HER3 expression on the cell surface (1+, 2+ or 3+) of the invasive component of tumour (either on archival tissue or a fresh biopsy) using an analytically validated IHC assay by central laboratory.
  • Histologically or cytologically confirmed diagnosis of solid tumour malignancy for which no standard therapeutic alternatives exist.
  • Adequate baseline organ functions
  • Left ventricular ejection fraction (LVEF) >=50% by Echocardiogram (ECHO) or Multi gated acquisition scan (MUGA).
  • Subjects must have at least two measurable lesions on Computed tomography (CT) or Magnetic resonance imaging (MRI) scan with a shortest axis of at least 20 millimeter (mm).

Exclusion Criteria:

  • Subjects with leptomeningeal or brain metastases or spinal cord compression
  • Prior HER3- directed treatment (HER2- or EGFR-directed treatment is acceptable).
  • Unresolved toxicity greater than National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0 Grade 1 from previous anti-cancer therapy
  • Known or suspected hypersensitivity reaction to prior biologic therapy
  • Evidence of another active malignancy (excludes non-melanoma skin cancer).
  • Concurrent medical condition that would jeopardize compliance with the protocol.
  • Receiving concurrent anti-tumor therapies, or chronic immunosuppressive therapies (includes daily steroid doses in excess of 20 milligram (mg)/day of prednisolone).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02345174
Other Study ID Numbers  ICMJE 200980
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: https://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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)
PRS Account GlaxoSmithKline
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP