Clinical trial NCT03291379: Vandetanib-eluting Radiopaque Embolic Beads in Patients With Resectable Liver Malignancies
Official title: VEROnA: A Window of Opportunity Study of Vandetanib-eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Carcinoma, Hepatocellular
Metastatic Colorectal Cancer
Keywords: mCRC, HCC, radiopaque beads, vandetanib
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
Collaborators: name: Biocompatibles UK Ltd
First posted: 2017-09-25
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 1 mL BTG-002814 containing 100 mg vandetanib
Primary purpose: TREATMENT

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.

Detailed description: A pilot open-label single arm multicenter phase 0 window of opportunity study of BTG-002814 given up to 3 weeks prior to surgery in up to 12 patients with resectable Hepatocellular carcinoma (HCC) or Colorectal cancer (CRC) with liver metastases.

Eligibility criteria: Inclusion Criteria:

1. Male or female adults (≥ 18 years old)
2. 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
3. Patients with low risk for surgical morbidity and mortality from liver surgery according to the investigators judgement
4. World Health Organization (WHO) performance status 0, 1 or 2
5. Adequate haematological function with Hb \>90 g/L, absolute neutrophil count \>1.5 x 10\^9/L, Plt \>100 x 10\^9/L
6. 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
7. 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).
8. Patient is willing to provide blood samples, and tissue samples at surgical resection, for research purposes
9. Patient is willing and able to provide written informed consent

Exclusion Criteria:

1. Any systemic chemotherapy within 3 months of the screening visit or any plan to administer systemic chemotherapy prior to surgery
2. 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
3. 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
4. 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)
5. Women of childbearing potential not using effective contraception or women who are breast feeding
6. Confirmed allergy to iodine-based intravenous contrast media
7. Patients who cannot have CT, MRI or dynamic contrast-enhanced (DCE) MRI Imaging (according to site policy)
8. Active uncontrolled cardiovascular disease
9. 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
10. 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
11. Patients who have participated in another clinical trial with an investigational product within 4 weeks prior to the screening visit

Primary outcomes:
measure: To Assess the Safety and Tolerability of Treatment With BTG-002814
timeFrame: Continuously throughout the study totalling 9 weeks
measure: Maximum Concentration (Cmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814
timeFrame: 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)
measure: Concentration of Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814
timeFrame: Following surgical resection of tumour
measure: Time Taken to Reach the Maximum Concentration (Tmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814
timeFrame: 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)
measure: Concentration of Vandetanib and N-desmethyl Vandetanib in Plasma Over Time Until End of Study Following Treatment With BTG-002814
timeFrame: 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)
measure: Concentration of N-desmethyl Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814
timeFrame: Following surgical resection of tumour
Secondary outcomes:
measure: Evaluate the Anatomical Distribution of BTG-002814 on Non-contrast Enhanced Imaging Using 4D CT
timeFrame: 1 day after treatment
measure: Evaluation of Histopathological Features in the Surgical Specimen (Malignant and Non-malignant Liver Tissue) by Analysing Percentage of Tumour Necrosis and Viability
timeFrame: Post-surgery (tumour resection)
measure: Evaluation of Histopathological Features in the Surgical Specimen (Malignant and Non-malignant Liver Tissue) by Assessing Number of Participants With Any Vascular Changes.
timeFrame: Post-surgery (tumour resection)
measure: 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.
timeFrame: Baseline, pre-treatment, up to 3 days prior to surgical resection of tumour
Other outcomes:
measure: Study Blood Biomarkers With the Potential to Identify Patients Likely to Respond to Treatment With BTG-002814
timeFrame: Baseline, pre-treatment, 1 day after treatment, Up to 3 days prior to surgical resection, end of study (28-32 days post-surgery).
measure: Study Tissue Biomarkers to Explore Key Immune, Inflammatory and Drug Related Mechanisms
timeFrame: Baseline, pre-treatment, Up to 3 days prior to surgical resection.
Locations:
city: Bloomsbury
country: United Kingdom
facility: University College London Hospital
state: London
Study officials:
affiliation: University College, London
name: Professor Ricky Sharma
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.