Vandetanib-eluting Radiopaque Embolic Beads in Patients With Resectable Liver Malignancies

NCT03291379 | Completed Early Phase 1 Results

• 1 other identifier: BTG-002814-01
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot, open label single arm phase 0 window of opportunity study of vandetanib-eluting radiopaque beads in patients with resectable liver malignancies.

Conditions

Carcinoma, Hepatocellular; Metastatic Colorectal Cancer

Keywords

mCRC, HCC, radiopaque beads, vandetanib

Outcome Measures

Primary Outcomes (6)

• To Assess the Safety and Tolerability of Treatment With BTG-002814

  Adverse events (AEs) related to treatment with BTG-002814 using the National Cancer Institute- Common Terminology Criteria for Adverse Events- Version 4.0 (NCI-CTCAE v4.0)

  Continuously throughout the study totalling 9 weeks

• Maximum Concentration (Cmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814

  Pharmacokinetic (PK) analysis of participants plasma samples by liquid chromatography with tandem mass spectrometry at the following timepoints: pre-treatment, post treatment (2 hours, 4 hours, 24 hours), prior to surgery, and end of study to derive Cmax.

  pre-treatment, 2 hours post-treatment, 4 hours post treatment, 24 hours post treatment, prior to surgery, and end of study (28-32 days post-surgery)

• Concentration of Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814

  PK analysis of participants resected liver tissue samples by liquid chromatography with tandem mass spectrometry to determine vandetanib concentrations at the centre, middle, and edge of the tumour, as well as in the normal tissue surrounding the tumour (1cm away).

  Following surgical resection of tumour

• Time Taken to Reach the Maximum Concentration (Tmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814

  PK analysis of participants plasma samples by liquid chromatography with tandem mass spectrometry at the following timepoints: pre-treatment, post treatment (2 hours, 4 hours, 24 hours), prior to surgery, and end of study to derive Tmax

  pre-treatment, 2 hours post-treatment, 4 hours post treatment, 24 hours post treatment, prior to surgery, and end of study (28-32 days post-surgery)

• Concentration of Vandetanib and N-desmethyl Vandetanib in Plasma Over Time Until End of Study Following Treatment With BTG-002814

  PK analysis of participants plasma samples by liquid chromatography with tandem mass spectrometry at the following timepoints: pre-treatment, post treatment (2 hours, 4 hours, 24 hours), prior to surgery, and end of study to derive AUCEoS (area under the curve at end of study).

  pre-treatment, 2 hours post-treatment, 4 hours post treatment, 24 hours post treatment, prior to surgery, and end of study (28-32 days post-surgery)

• Concentration of N-desmethyl Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814

  PK analysis of participants resected liver tissue samples by liquid chromatography with tandem mass spectrometry to determine N-desmethyl vandetanib concentrations at the centre, middle, and edge of the tumour, as well as in the normal tissue surrounding the tumour (1cm away).

  Following surgical resection of tumour

Secondary Outcomes (4)

• Evaluate the Anatomical Distribution of BTG-002814 on Non-contrast Enhanced Imaging Using 4D CT

  1 day after treatment

• Evaluation of Histopathological Features in the Surgical Specimen (Malignant and Non-malignant Liver Tissue) by Analysing Percentage of Tumour Necrosis and Viability

  Post-surgery (tumour resection)

• Evaluation of Histopathological Features in the Surgical Specimen (Malignant and Non-malignant Liver Tissue) by Assessing Number of Participants With Any Vascular Changes.

  Post-surgery (tumour resection)

• Assessment of Changes in Blood Flow on Dynamic Contrast-Enhanced (DCE) MRI Following Treatment With BTG-002814. The Following Parameters Will be Derived From DCE-MRI Images: Ktrans, Kep and Ve.

  Baseline, pre-treatment, up to 3 days prior to surgical resection of tumour

Other Outcomes (2)

• Study Blood Biomarkers With the Potential to Identify Patients Likely to Respond to Treatment With BTG-002814

  Baseline, pre-treatment, 1 day after treatment, Up to 3 days prior to surgical resection, end of study (28-32 days post-surgery).

• Study Tissue Biomarkers to Explore Key Immune, Inflammatory and Drug Related Mechanisms

  Baseline, pre-treatment, Up to 3 days prior to surgical resection.

Study Arms (1)

BTG-002814

EXPERIMENTAL

Single arm: BTG-002814 (vandetanib-eluting radiopaque beads)

Drug: BTG-002814

Interventions

BTG-002814 DRUG

BTG-002814 containing 100 mg vandetanib

Also known as: vandetanib-eluting radiopaque beads

BTG-002814

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female adults (≥ 18 years old)
• Patient with resectable HCC (Child Pugh A, International Normalized Ratio (INR) ≤1.5) or resectable liver metastases from CRC and a candidate for liver surgery
• Patients with low risk for surgical morbidity and mortality from liver surgery according to the investigators judgement
• World Health Organization (WHO) performance status 0, 1 or 2
• Adequate haematological function with Hb \>90 g/L, absolute neutrophil count \>1.5 x 10\^9/L, Plt \>100 x 10\^9/L
• Adequate liver function with serum bilirubin \<1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) (or aspartate aminotransferase (AST) if ALT not available) ≤5 x ULN, alkaline phosphatase (ALP) \<5 x ULN
• Adequate renal function with serum creatinine ≤1.5 x ULN and calculated creatinine clearance (GFR) ≥50 mL/min estimated using a validated creatinine clearance calculation (e.g., Cockcroft-Gault or Wright formula).
• Patient is willing to provide blood samples, and tissue samples at surgical resection, for research purposes
• Patient is willing and able to provide written informed consent

You may not qualify if:

• Any systemic chemotherapy within 3 months of the screening visit or any plan to administer systemic chemotherapy prior to surgery
• Previous treatment with transarterial embolisation (with or without chemotherapy) of the liver, prior radiotherapy or ablation therapy to the liver or prior yttrium-90 microsphere therapy
• Any contraindication to vandetanib according to its local label including:
• Hypersensitivity to the active substance
• Congenital long corrected QT interval (QTc) syndrome
• Patients known to have a QTc interval over 480 milliseconds
• Concomitant use of medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes
• Any contraindication to hepatic artery catheterisation or hepatic embolisation procedures (e.g. portal venous thrombosis, severely reduced portal venous flow or hepatofugal blood flow, untreated varices at high risk of bleeding)
• Women of childbearing potential not using effective contraception or women who are breast feeding
• Confirmed allergy to iodine-based intravenous contrast media
• Patients who cannot have CT, MRI or dynamic contrast-enhanced (DCE) MRI Imaging (according to site policy)
• Active uncontrolled cardiovascular disease
• Any co-morbid disease or condition or event that, in the investigator's judgment, would place the patient at undue risk and would preclude the safe use of BTG-002814
• Levels of potassium, calcium, magnesium or thyroid stimulating hormone (TSH) outside the normal ranges, and that in the investigator's judgement are clinically significant, or other laboratory findings that in the view of the investigator makes it undesirable for the patient to participate in the study
• Patients who have participated in another clinical trial with an investigational product within 4 weeks prior to the screening visit

Sponsors & Collaborators

• Boston Scientific Corporation: lead
• Biocompatibles UK Ltd: collaborator

Study Sites (1)

University College London Hospital

Bloomsbury, London, NW1 2BU, United Kingdom

Location

Related Publications (1)

• 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 JA, Lewis AL, 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 Oct 2;8(10):e13696. doi: 10.2196/13696.

  PMID: 31579027 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Sarah Cooper
• Organization: Biocompatibles UK Ltd

Sarah-Jane.Cooper@bsci.com

07805354224

Study Officials

• Professor Ricky Sharma

  University College, London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 1 mL BTG-002814 containing 100 mg vandetanib

Study Record Dates

• First Submitted: May 17, 2017
• First Posted: September 25, 2017
• Study Start: May 17, 2017
• Primary Completion: August 3, 2019
• Study Completion: August 3, 2019
• Last Updated: July 19, 2021
• Results First Posted: February 3, 2021

Record last verified: 2021-07

Locations

GB (1)