VEROnA: A Window of Opportunity Study of Vandetanib-eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Maximum Concentration (Cmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
BTG-002814
Single arm: BTG-002814 (vandetanib-eluting radiopaque beads)
干预措施: BTG-002814 (Drug)
结局指标
主要结局
Maximum Concentration (Cmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814
时间窗: 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.
Concentration of Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814
时间窗: 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).
Time Taken to Reach the Maximum Concentration (Tmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814
时间窗: 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
To Assess the Safety and Tolerability of Treatment With BTG-002814
时间窗: 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)
Concentration of N-desmethyl Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814
时间窗: 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).
Concentration of Vandetanib and N-desmethyl Vandetanib in Plasma Over Time Until End of Study Following Treatment With BTG-002814
时间窗: 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).
次要结局
- 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)