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Accepted for/Published in: JMIR Research Protocols

Date Submitted: Mar 21, 2019
Date Accepted: Jul 16, 2019

The final, peer-reviewed published version of this preprint can be found here:

VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies

Beaton L, Tregidgo HFJ, Znati SA, Forsyth S, Clarkson MJ, Bandula S, Chouhan M, Lowe HL, Zaw Thin M, Hague J, Sharma D, Pollok JM, Davidson BR, Raja J, Munneke G, Stuckey DJ, Bascal ZA, Wilde PE, Cooper S, Ryan S, Czuczman P, Boucher E, Hartley J, Lewis A, Jansen M, Meyer T, Sharma RA

VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies

JMIR Res Protoc 2019;8(10):e13696

DOI: 10.2196/13696

PMID: 31579027

PMCID: 6777276

Protocol Paper VEROnA protocol: a pilot, open label, single-arm, phase 0, window-of-opportunity study of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies

  • Laura Beaton; 
  • Henry F. J. Tregidgo; 
  • Sami A. Znati; 
  • Sharon Forsyth; 
  • Matthew J. Clarkson; 
  • Steven Bandula; 
  • Manil Chouhan; 
  • Helen L. Lowe; 
  • May Zaw Thin; 
  • Julian Hague; 
  • Dinesh Sharma; 
  • Joerg M Pollok; 
  • Brian R Davidson; 
  • Jowad Raja; 
  • Graham Munneke; 
  • Daniel J Stuckey; 
  • Zainab A Bascal; 
  • Paul E. Wilde; 
  • Sarah Cooper; 
  • Samantha Ryan; 
  • Peter Czuczman; 
  • Eveline Boucher; 
  • John Hartley; 
  • Andrew Lewis; 
  • Marnix Jansen; 
  • Tim Meyer; 
  • Ricky A. Sharma

ABSTRACT

Background:

Transarterial chemoembolisation (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer (mCRC). However, TACE is not a curative treatment, and tumour progression occurs in more than half of patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads (DEB)-TACE, the clinical efficacy of TACE has not been optimised and improved arterial therapies are required.

Objective:

The primary objectives of the VEROnA study are to evaluate the safety and tolerability of vandetanib-eluting radiopaque (RO) embolic beads (BTG-002814) in patients with resectable liver malignancies, and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver following treatment with BTG-002814.

Methods:

The VEROnA study is a first-in-human, open-label, single-arm, phase 0, window-of-opportunity study of BTG-002814 (containing 100 mg vandetanib) delivered trans arterially, 7 to 21 days prior to surgery in patients with resectable liver malignancies. Eligible patients have a diagnosis of colorectal liver metastases, or hepatocellular carcinoma (Childs Pugh A), diagnosed histologically or radiologically, and are candidates for liver surgery. All patients are followed up for 28 days following surgery. Secondary objectives are to evaluate the anatomical distribution of BTG-002814 on non-contrast enhanced imaging, to evaluate histopathological features in the surgical specimen and to assess changes in blood flow on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) following treatment with BTG-002814. Exploratory objectives are to study blood biomarkers with the potential to identify patients likely to respond to treatment, and to correlate the distribution of BTG-002814 on imaging with pathology by 3D modelling.

Results:

Enrolment for the study will complete in February 2019. Results of a planned interim analysis were reviewed by a safety committee after the first three patients completed follow-up. The recommendation of the committee was to continue the study without any changes to the dose, or trial design, as there were no significant unexpected toxicities related to BTG-002814.

Conclusions:

The VEROnA study is studying the feasibility of administering BTG-002814 in order to optimise the use of this novel technology as liver-directed therapy for patients with primary and secondary liver cancer. Clinical Trial: NCT03291379; https://clinicaltrials.gov/ct2/show/NCT03291379


 Citation

Please cite as:

Beaton L, Tregidgo HFJ, Znati SA, Forsyth S, Clarkson MJ, Bandula S, Chouhan M, Lowe HL, Zaw Thin M, Hague J, Sharma D, Pollok JM, Davidson BR, Raja J, Munneke G, Stuckey DJ, Bascal ZA, Wilde PE, Cooper S, Ryan S, Czuczman P, Boucher E, Hartley J, Lewis A, Jansen M, Meyer T, Sharma RA

VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies

JMIR Res Protoc 2019;8(10):e13696

DOI: 10.2196/13696

PMID: 31579027

PMCID: 6777276

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