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

• Sponsor: Boston Scientific Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03291379
• Collaborator: Biocompatibles UK Ltd (Industry)
• Enrollment: 8
• Location: 1
• Arm: 1
• Actual Duration (Months): 26.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular; Metastatic Colorectal Cancer	Drug: BTG-002814	Early Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: 1 mL BTG-002814 containing 100 mg vandetanib1 mL BTG-002814 containing 100 mg vandetanib
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: VEROnA: A Window of Opportunity Study of Vandetanib-eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies
• Actual Study Start Date: May 17, 2017
• Actual Primary Completion Date: Aug 3, 2019
• Actual Study Completion Date: Aug 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BTG-002814 Single arm: BTG-002814 (vandetanib-eluting radiopaque beads)	Drug: BTG-002814; BTG-002814 containing 100 mg vandetanib; Other Names: vandetanib-eluting radiopaque beads

Outcome Measures

Primary Outcome Measures

1. To Assess the Safety and Tolerability of Treatment With BTG-002814 [Continuously throughout the study totalling 9 weeks]

   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)

2. Maximum Concentration (Cmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814 [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)]

   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.

3. Concentration of Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814 [Following surgical resection of tumour]

   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).

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

   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

5. Concentration of Vandetanib and N-desmethyl Vandetanib in Plasma Over Time Until End of Study Following Treatment With BTG-002814 [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)]

   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).

6. Concentration of N-desmethyl Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814 [Following surgical resection of tumour]

   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).

Secondary Outcome Measures

1. Evaluate the Anatomical Distribution of BTG-002814 on Non-contrast Enhanced Imaging Using 4D CT [1 day after treatment]

   An automated thresholding and filtering algorithm was designed to allow the volume of delivered beads to be quantitatively determined for regions of interest (liver, registered sample, tumour, tumour dilated 1cm, tumour dilated 2cm) from the pre-surgical non-contrast CT scan and the PET/CT of the explanted liver samples following surgery.

2. 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)]

   An evaluation of histopathological features in both malignant and non-malignant liver tissue from the surgical specimen was performed by microscopic examination. Sections of resected liver tissue was paraffin-embedded and Hematoxylin and Eosin (H&E) slides were produced. The H&E slides were scanned to produce 3D pathology models of tumour volume and compared to the 3D models generated from clinical imaging. This allowed the extent of tumour necrosis and viable tumour to be determined.

3. 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)]

   An evaluation of histopathological features in both malignant and non-malignant liver tissue from the surgical specimen was performed by microscopic examination. Sections of resected liver tissue was paraffin-embedded and Hematoxylin and Eosin (H&E) slides were produced. The H&E slides were scanned to produce 3D pathology models of tumour volume and compared to the 3D models generated from clinical imaging. This allowed any vascular changes to be determined.

4. 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]

   After acquisition of DCE-MRI liver sequences, tumour signal intensity curves were used to calculate tissue parameters describing tumour perfusion, blood flow and vascularity, before and following treatment with BTG 002814. Bland Altman analysis showed the variability between baseline and pre-treatment readings to be too high, so an interpretation of the changes in blood flow prior to surgery is unreliable.

Other Outcome Measures

1. 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).]

   The following serum biomarkers were measured at Baseline, pre-treatment, 1 day after treatment, Up to 3 days prior to surgical resection, end of study ; cytokines, chemokines and growth factors relevant to cancer and inflammation.

2. Study Tissue Biomarkers to Explore Key Immune, Inflammatory and Drug Related Mechanisms [Baseline, pre-treatment, Up to 3 days prior to surgical resection.]

   The following tissue biomarkers were measured at Baseline, pre-treatment, Up to 3 days prior to surgical resection; Levels of serum alpha-fetoprotein (AFP) in patients with HCC. Levels of serum Carcinoembryonic Antigen (CEA), Cancer Antigen (CA)19-9 and CA-125 in patients with metastatic colorectal cancer (mCRC).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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)

2. Women of childbearing potential not using effective contraception or women who are breast feeding

3. Confirmed allergy to iodine-based intravenous contrast media

4. Patients who cannot have CT, MRI or dynamic contrast-enhanced (DCE) MRI Imaging (according to site policy)

5. Active uncontrolled cardiovascular disease

6. 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

7. 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

8. Patients who have participated in another clinical trial with an investigational product within 4 weeks prior to the screening visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University College London Hospital	Bloomsbury	London	United Kingdom	NW1 2BU

Sponsors and Collaborators

• Boston Scientific Corporation
• Biocompatibles UK Ltd

Investigators

• Principal Investigator: Professor Ricky Sharma, University College, London

Study Documents (Full-Text)

• Study Protocol - Dec 3, 2018
• Statistical Analysis Plan - May 16, 2019

More Information

Publications

None provided.

• Responsible Party: Boston Scientific Corporation
• ClinicalTrials.gov Identifier: NCT03291379
• Other Study ID Numbers: BTG-002814-01
• First Posted: Sep 25, 2017
• Last Update Posted: Jul 19, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Boston Scientific Corporation: mCRC, HCC, radiopaque beads, vandetanib
• Additional relevant MeSH terms: Carcinoma, Hepatocellular

Study Results

Participant Flow

Arm/Group Title	BTG-002814
Arm/Group Description	Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	BTG-002814
Arm/Group Description	Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib
Overall Participants	8
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62.5
Sex: Female, Male (Count of Participants)
Female	1 12.5%
Male	7 87.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	7 87.5%
More than one race	0 0%
Unknown or Not Reported	1 12.5%
Region of Enrollment (participants) [Number]
United Kingdom	8 100%
World Health Organisation (WHO) Performance Status (Count of Participants)
Grade 0 (asymptomatic)	8 100%
Grade 1 (Symptomatic, but ambulatory)	0 0%
Grade 2 (Symptomatic, <50% in bed)	0 0%
Tumour type (Count of Participants)
Hepatocellular carcinoma (HCC)	2 25%
Metastatic colorectal cancer (mCRC)	6 75%
Number of liver lesions (Count) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Count]	1.6 (1.4)

Outcome Measures

1. Primary Outcome

Title	To Assess the Safety and Tolerability of Treatment With BTG-002814
Description	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)
Time Frame	Continuously throughout the study totalling 9 weeks

Outcome Measure Data

Analysis Population Description

Safety population - all participants treated with BTG-002814

Arm/Group Title	BTG-002814
Arm/Group Description	Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib
Measure Participants	8
participants with treatment emergent Adverse Events (AEs)	8 100%
participants with treatment emergent Serious Adverse Events (SAEs)	4 50%

2. Primary Outcome

Title	Maximum Concentration (Cmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

all participants treated with BTG-002814

Arm/Group Title	BTG-002814
Arm/Group Description	Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib
Measure Participants	8
Vandetanib Plasma Cmax	24.3 (13.94)
N-desmethyl Plasma Cmax	0.6 (0.82)

3. Primary Outcome

Title	Concentration of Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814
Description	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).
Time Frame	Following surgical resection of tumour

Outcome Measure Data

Analysis Population Description

Results were not available for 2 patients where sample was incorrectly prepared, or no sample was received. For patients with multiple tumours, only the treated tumours were sampled and analysed. The results for this outcome measure are reported by individual subject (where data was available) by each sample location (centre, middle, edge of the tumour or 1cm away from tumour) per row.

Arm/Group Title	BTG-002814
Arm/Group Description	Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib
Measure Participants	6
Subject 01: Vandetanib concentration centre of tumour	404000
Subject 01: Vandetanib concentration middle of tumour	394000
Subject 01: Vandetanib concentration edge of tumour	327000
Subject 01: Vandetanib concentration 1cm away from tumour	10800
Subject 03: Vandetanib concentration centre of tumour	8510
Subject 03: Vandetanib concentration middle of tumour	11000
Subject 03: Vandetanib concentration edge of tumour	18800
Subject 03: Vandetanib concentration 1cm away from tumour	9120
Subject 05: Vandetanib concentration centre of tumour	7340
Subject 05: Vandetanib concentration middle of tumour	7550
Subject 05: Vandetanib concentration edge of tumour	12500
Subject 05: Vandetanib concentration 1cm away from tumour	7090
Subject 06: Vandetanib concentration centre of tumour	160000
Subject 06: Vandetanib concentration middle of tumour	151000
Subject 06: Vandetanib concentration edge of tumour	11100
Subject 06: Vandetanib concentration 1cm away from tumour	1480
Subject 07: Vandetanib concentration centre of tumour	4570
Subject 07: Vandetanib concentration middle of tumour	531
Subject 07: Vandetanib concentration edge of tumour	441
Subject 07: Vandetanib concentration 1cm away from tumour	2760
Subject 08: Vandetanib concentration centre of tumour	1140
Subject 08 (1cm lesion): whole tumour Vandetanib concentration	93500
Subject 08 (inferior lesion): Vandetanib concentration centre of tumour	6180
Subject 08: Vandetanib concentration middle of tumour	1240
Subject 08 (inferior lesion): Vandetanib concentration middle of tumour	1440
Subject 08: Vandetanib concentration edge of tumour	2840
Subject 08 (inferior lesion): Vandetanib concentration edge of tumour	2710
Subject 08: Vandetanib concentration 1cm away from tumour	29100
Subject 08 (1 cm lesion): Vandetanib concentration 1cm away from tumour	5350
Subject 08 (inferior lesion): Vandetanib concentration 1cm away from tumour	6010

4. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

all participants treated with BTG-002814

Arm/Group Title	BTG-002814
Arm/Group Description	Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814: BTG-002814 containing 100 mg vandetanib
Measure Participants	8
Vandetanib Plasma Tmax	26.0 (67.08)
N-desmethyl Plasma Tmax	0.8 (1.04)

5. Primary Outcome

Title	Concentration of Vandetanib and N-desmethyl Vandetanib in Plasma Over Time Until End of Study Following Treatment With BTG-002814
Description	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).
Time Frame	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)

Outcome Measure Data

Analysis Population Description

all participants treated with BTG-002814

Arm/Group Title	BTG-002814
Arm/Group Description	Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib
Measure Participants	8
Vandetanib Plasma AUCEoS	6979.3 (3188.21)
N-desmethyl Plasma AUCEoS	81.1 (169.40)

6. Primary Outcome

Title	Concentration of N-desmethyl Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814
Description	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).
Time Frame	Following surgical resection of tumour

Outcome Measure Data

Analysis Population Description

Results were not available for 2 patients where sample was incorrectly prepared, or no sample was received. For patients with multiple tumours, only the treated tumours were sampled and analysed. The results for this outcome measure are reported by individual subject (where data was available), by each sample location (centre, middle, edge of the tumour, 1cm away from tumour) per row.

Arm/Group Title	BTG-002814
Arm/Group Description	Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib
Measure Participants	6
Subject 01: N-desmethyl Vandetanib concentration centre of tumour	4620
Subject 01: N-desmethyl Vandetanib concentration middle of tumour	4740
Subject 01: N-desmethyl Vandetanib concentration edge of tumour	3680
Subject 01: N-desmethyl Vandetanib concentration 1cm away from tumour	280
Subject 03: N-desmethyl concentration centre of tumour	69.6
Subject 03: N-desmethyl Vandetanib concentration middle of tumour	59.8
Subject 03: N-desmethyl Vandetanib concentration edge of tumour	69.2
Subject 03: N-desmethyl Vandetanib concentration 1cm away from tumour	831
Subject 05: N-desmethyl concentration centre of tumour	421
Subject 05: N-desmethyl Vandetanib concentration middle of tumour	418
Subject 05: N-desmethyl Vandetanib concentration edge of tumour	469
Subject 05: N-desmethyl Vandetanib concentration 1cm away from tumour	544
Subject 06: N-desmethyl concentration centre of tumour	113
Subject 06: N-desmethyl Vandetanib concentration middle of tumour	93.9
Subject 06: N-desmethyl Vandetanib concentration edge of tumour	11.4
Subject 06: N-desmethyl Vandetanib concentration 1cm away from tumour	55.6
Subject 07: N-desmethyl concentration centre of tumour	21
Subject 07: N-desmethyl Vandetanib concentration middle of tumour	15.7
Subject 07: N-desmethyl Vandetanib concentration edge of tumour	28.7
Subject 07: N-desmethyl Vandetanib concentration 1cm away from tumour	84
Subject 08: N-desmethyl concentration centre of tumour	39.3
Subject 08 (1cm lesion): whole tumour N-desmethyl concentration	208
Subject 08 (inferior lesion): N-desmethyl concentration centre of tumour	80.2
Subject 08: N-desmethyl Vandetanib concentration middle of tumour	57.1
Subject 08 (inferior lesion): N-desmethyl Vandetanib concentration middle of tumour	101
Subject 08: N-desmethyl Vandetanib concentration edge of tumour	145
Subject 08 (inferior lesion): N-desmethyl Vandetanib concentration edge of tumour	171
Subject 08: N-desmethyl Vandetanib concentration 1cm away from tumour	389
Subject 08 (1 cm lesion): N-desmethyl Vandetanib concentration 1cm away from tumour	342
Subject 08 (inferior lesion): N-desmethyl Vandetanib concentration 1cm away from tumour	405

7. Secondary Outcome

Title	Evaluate the Anatomical Distribution of BTG-002814 on Non-contrast Enhanced Imaging Using 4D CT
Description	An automated thresholding and filtering algorithm was designed to allow the volume of delivered beads to be quantitatively determined for regions of interest (liver, registered sample, tumour, tumour dilated 1cm, tumour dilated 2cm) from the pre-surgical non-contrast CT scan and the PET/CT of the explanted liver samples following surgery.
Time Frame	1 day after treatment

Outcome Measure Data

Analysis Population Description

All 8 subjects treated with BTG-002814 were analysed, however, not all subjects have sampling of all regions (liver, registered sample, tumour, tumour dilated 1cm, tumour dilated 2cm) due to some samples not being able to be accurately processed and registered. The data for this outcome measure is reported by individual subject, for each sample region (where data is available) per row.

Arm/Group Title	BTG-002814
Arm/Group Description	Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib
Measure Participants	8
Subject 01: Liver	928.83
Subject 01: Registered sample	399.27
Subject 01: Tumour	361.14
Subject 01: tumour dilated 1cm	393.79
Subject 01: Tumour dilated 2cm	479.28
Subject 02: Liver	764.69
Subject 02: Tumour	596.78
Subject 02: Tumour dilated 1cm	617.72
Subject 02: Tumour dilated 2cm	649.97
Subject 03: Liver	594.79
Subject 03: Registered sample	116.54
Subject 03: Tumour	0.32
Subject 03: Tumour dilated 1cm	36.26
Subject 03: Tumour dilated 2cm	108.85
Subject 04: Liver	852.03
Subject 05: Liver	849.29
Subject 05: Registered sample	751.62
Subject 05: Tumour	0
Subject 5: Tumour dilated 1cm	15.26
Subject 05: Tumour dilated 2cm	86.28
Subject 06: Liver	202.56
Subject 06: Registered sample	148.09
Subject 06: Tumour	51.14
ubject 06: Tumour dilated 1cm	115.39
Subject 06: Tumour dilated 2cm	166.80
Subject 07: Liver	720.78
Subject 07: Registered sample	103.82
Subject 07: Tumour	4.32
Subject 07: Tumour dilated 1cm	75.43
Subject 07: Tumour dilated 2cm	133.26
Subject 08: Liver	693.73
Subject 08: Registered sample	422.37
Subject 08: Tumour	21.87
Subject 08: Tumour dilated 1cm	264.90
Subject 08: Tumour dilated 2cm	378.15

8. Secondary Outcome

Title	Evaluation of Histopathological Features in the Surgical Specimen (Malignant and Non-malignant Liver Tissue) by Analysing Percentage of Tumour Necrosis and Viability
Description	An evaluation of histopathological features in both malignant and non-malignant liver tissue from the surgical specimen was performed by microscopic examination. Sections of resected liver tissue was paraffin-embedded and Hematoxylin and Eosin (H&E) slides were produced. The H&E slides were scanned to produce 3D pathology models of tumour volume and compared to the 3D models generated from clinical imaging. This allowed the extent of tumour necrosis and viable tumour to be determined.
Time Frame	Post-surgery (tumour resection)

Outcome Measure Data

Analysis Population Description

all participants treated with BTG-002814

Arm/Group Title	BTG-002814
Arm/Group Description	Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib
Measure Participants	8
Tumour necrosis	92.5
Viable tumour	7.5

9. Secondary Outcome

Title	Evaluation of Histopathological Features in the Surgical Specimen (Malignant and Non-malignant Liver Tissue) by Assessing Number of Participants With Any Vascular Changes.
Description	An evaluation of histopathological features in both malignant and non-malignant liver tissue from the surgical specimen was performed by microscopic examination. Sections of resected liver tissue was paraffin-embedded and Hematoxylin and Eosin (H&E) slides were produced. The H&E slides were scanned to produce 3D pathology models of tumour volume and compared to the 3D models generated from clinical imaging. This allowed any vascular changes to be determined.
Time Frame	Post-surgery (tumour resection)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BTG-002814
Arm/Group Description	Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib
Measure Participants	8
Vascular changes absent	8 100%
Vascular changes present	0 0%

10. Secondary Outcome

Title	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.
Description	After acquisition of DCE-MRI liver sequences, tumour signal intensity curves were used to calculate tissue parameters describing tumour perfusion, blood flow and vascularity, before and following treatment with BTG 002814. Bland Altman analysis showed the variability between baseline and pre-treatment readings to be too high, so an interpretation of the changes in blood flow prior to surgery is unreliable.
Time Frame	Baseline, pre-treatment, up to 3 days prior to surgical resection of tumour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Other Pre-specified Outcome

Title	Study Blood Biomarkers With the Potential to Identify Patients Likely to Respond to Treatment With BTG-002814
Description	The following serum biomarkers were measured at Baseline, pre-treatment, 1 day after treatment, Up to 3 days prior to surgical resection, end of study ; cytokines, chemokines and growth factors relevant to cancer and inflammation.
Time Frame	Baseline, pre-treatment, 1 day after treatment, Up to 3 days prior to surgical resection, end of study (28-32 days post-surgery).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Other Pre-specified Outcome

Title	Study Tissue Biomarkers to Explore Key Immune, Inflammatory and Drug Related Mechanisms
Description	The following tissue biomarkers were measured at Baseline, pre-treatment, Up to 3 days prior to surgical resection; Levels of serum alpha-fetoprotein (AFP) in patients with HCC. Levels of serum Carcinoembryonic Antigen (CEA), Cancer Antigen (CA)19-9 and CA-125 in patients with metastatic colorectal cancer (mCRC).
Time Frame	Baseline, pre-treatment, Up to 3 days prior to surgical resection.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From date participant signed Informed Consent until the patient's last visit (up to 9 weeks) (or after this date if the site Investigator feels the event is related to study treatment)
Arm/Group Title	BTG-002814
Arm/Group Description	Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib
All Cause Mortality
	BTG-002814
	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)
Serious Adverse Events
	BTG-002814
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
Gastrointestinal disorders
Ileus	1/8 (12.5%)	1
Upper gastrointestinal hemorrhage	1/8 (12.5%)	1
Hepatobiliary disorders
Ascites	1/8 (12.5%)	1
Post procedural bile leak	1/8 (12.5%)	1
Infections and infestations
Lung infection	1/8 (12.5%)	1
Postoperative wound infection	2/8 (25%)	2
Sepsis	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Abdominal wound dehiscence	1/8 (12.5%)	1
Renal and urinary disorders
Renal failure acute	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	BTG-002814
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
Cardiac disorders
Bradycardia	3/8 (37.5%)	5
Cardiac signs and symptoms NEC	1/8 (12.5%)	1
Sinus bradycardia	2/8 (25%)	2
Ear and labyrinth disorders
Tinnitus	2/8 (25%)	2
Gastrointestinal disorders
Abdominal distension	1/8 (12.5%)	2
Abdominal pain	8/8 (100%)	19
Constipation	5/8 (62.5%)	6
Diarrhoea	1/8 (12.5%)	1
Dry mouth	1/8 (12.5%)	1
Dyspepsia	5/8 (62.5%)	8
Gastritis	2/8 (25%)	2
Gastrooesophageal reflux disease	2/8 (25%)	2
Nausea	5/8 (62.5%)	8
Vomiting	2/8 (25%)	2
General disorders
Fatigue	7/8 (87.5%)	23
Influenza like illness	1/8 (12.5%)	1
Non-cardiac chest pain	1/8 (12.5%)	1
Pain	2/8 (25%)	2
Pyrexia	2/8 (25%)	2
Infections and infestations
Lung infection	1/8 (12.5%)	1
Postoperative wound infection	2/8 (25%)	3
Investigations
Alanine aminotransferase	5/8 (62.5%)	8
Aspartate aminotransferase	5/8 (62.5%)	7
Blood albumin	3/8 (37.5%)	25
Blood alkaline phosphatase	5/8 (62.5%)	5
Blood bilirubin	1/8 (12.5%)	1
Blood calcium	2/8 (25%)	2
Blood creatinine	2/8 (25%)	7
Blood glucose	5/8 (62.5%)	8
Blood lactic acid	1/8 (12.5%)	1
Blood magnesium	1/8 (12.5%)	1
Blood sodium	1/8 (12.5%)	1
Blood thyroid stimulating hormone	2/8 (25%)	2
Blood urea	2/8 (25%)	2
Blood uric acid	4/8 (50%)	6
C-reactive protein	1/8 (12.5%)	14
Electrocardiogram QT prolonged	2/8 (25%)	4
Gamma-glutamyl transferase	5/8 (62.5%)	8
Glomerular filtration rate	1/8 (12.5%)	1
Haemoglobin	8/8 (100%)	15
International normalized ratio	1/8 (12.5%)	1
Neutrophil count	1/8 (12.5%)	11
Neutrophil count decreased	4/8 (50%)	6
Platelet count	2/8 (25%)	2
Weight decreased	3/8 (37.5%)	3
White blood cell count	2/8 (25%)	14
Metabolism and nutrition disorders
Decreased appetite	5/8 (62.5%)	7
Dehydration	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/8 (25%)	2
Back pain	2/8 (25%)	2
Groin pain	1/8 (12.5%)	2
Myalgia	1/8 (12.5%)	1
Nervous system disorders
Paraesthesia	2/8 (25%)	2
Psychiatric disorders
Delirium	1/8 (12.5%)	1
Insomnia	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/8 (25%)	2
Dysphonia	1/8 (12.5%)	1
Dyspnoea	2/8 (25%)	2
Hiccups	2/8 (25%)	2
Laryngeal inflammation	1/8 (12.5%)	1
Oropharyngeal pain	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Dermatitis acneiform	1/8 (12.5%)	1
Pruritus	1/8 (12.5%)	1
Rash	1/8 (12.5%)	1
Vascular disorders
Haematoma	1/8 (12.5%)	2
Hypertension	7/8 (87.5%)	12
Hypotension	3/8 (37.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.