Hepatocellular Carcinoma (HCC) MedDRA version: 20.0 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 100000004864
Conditions
Interventions
Product Name: Vandetanib Eluting Radiopaque Bead
Product Code: BTG-002814
Pharmaceutical Form: Implant
Sponsors
Biocompatibles UK Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female adults (=18 years old) 2. Primary confirmed diagnosis of HCC according to the EASL criteria or histology 3. Patient is a candidate for TACE and is not eligible or amenable for curative treatment (resection, liver transplantation or percutaneous ablation) 4. Part A: Patients with unilobar tumours. Patient must have a single tumour diameter of 5 cm or more or multiple tumours with the sum of the diameters being 8 cm or more Part B: Patients with unilobar or bilobar tumours. For bilobar tumours, both lobes must be able to be treated in the same session 5. Measurable disease according to mRECIST and RECIST 1.1 6. Performance Status ECOG 0 or 1 7. Part A: Patients with well preserved liver function (Child-Pugh A with no clinically detectable ascites, or if minor ascites on imaging, the patients must have no diuretic medication). Part B: Patients with Child-Pugh A or B7 8. Adequate haematological function with Hb >90 g/L, absolute neutrophil count (ANC) >1.5 x 109/L, Plt >75 x 109/L, INR =1.5 9. Adequate liver function with serum bilirubin 28 g/L 10. 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. Cockroft-Gault or Wright formula). 11. Patient is able and willing to participate in the study and has provided written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 28 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: 1. Advanced tumoural disease, vascular invasion (VP3, VP4) of the tumour extrahepatic spread 2. Patients previously treated in the same liver lobe with transarterial embolisation (with or without chemotherapy) of the liver, prior radiotherapy or prior yttrium-90 microsphere therapy 3. Patients who are currently on the liver transplant waiting list 4. Part A: Patients with bilobar disease 5. Part A: Advanced liver disease patients who are Child-Pugh >A6 or who have active gastrointestinal bleeding Part B: Advanced liver disease patients who are Child-Pugh >B7 or who have active gastrointestinal bleeding 6. Any contraindication to vandetanib according to its label including: a.Hypersensitivity to the active substance b. Congenital long QTc syndrome. c. Patients known to have a QTc interval over 480 milliseconds. d. Concomitant use of medicinal products also known to also prolong the QTc interval and/or induce Torsades de pointes (See Appendix 1) 7. 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) biliary obstruction, bilio-enteric anastomosis and incompetent ampulla of vater 8. Women of childbearing potential not using effective contraceptive methods or women who are breast feeding 9. Confirmed allergy to iodine-based intravenous contrast media that cannot be managed with standard of care 10. Any co-morbid disease or condition or event that, in the Investigator’s judgment, would place the patient at undue risk, that and would preclude the safe use of treatment with BTG-002814 11. Patients who cannot have Computerized Tomography (CT) imaging (according to site policy) 12. 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 laboratory findings that in the view of the Investigator makes it undesirable for the patient to participate in the study 13. History of second malignancy (except those treated with curative intent for more than three years previously without relapse) and non-melanoma skin cancer or cervical carcinoma in situ 14. Patients who have received treatment in another clinical study with an investigational product within 4 weeks prior to the screening visit. 15. Concomitant treatment with any other anti cancer treatment (chemotherapy, targeted therapy, immunotherapy, Chinese medicine) 16. Patients previously treated with any systemic anti-cancer therapy for HCC
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of BTG-002814 To identify the Recommended Dose (RD) of BTG-002814 ;Secondary Objective: To evaluate the pharmacokinetics of vandetanib and the N-desmethyl metabolite To assess the anti-tumour activity according to Modified Response Evaluation Criteria in Solid Tumours (mRECIST) and Response Evaluation Criteria in Solid Tumours (RECIST 1.1) criteria To evaluate the changes in serum alpha fetoprotein (AFP) levels following treatment with BTG-002814 ;Primary end point(s): Adverse Events (AEs) related to treatment with BTG-002814 using the standardised grading criteria (National Cancer Institute-Common Terminology Criteria for Adverse Events-Version 4.0 (NCI-CTCAE v4.0));Timepoint(s) of evaluation of this end point: Adverse events: Part A - At all visits from treatment to end of study (up to 7 weeks) Part B - At all visits from treatment to end of study (up to 26 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PK profile of vandetanib and the N-desmethyl metabolite Objective response rate (ORR) according to mRECIST and RECIST 1.1 at 4 weeks, 3 and 6 months following first treatment Time to progression (TTP) according to mRECIST and RECIST 1.1 Disease Control Rate (DCR) according to mRECIST and RECIST 1.1 at 4 weeks, 3 and 6 months following first treatment Change in AFP levels from baseline Blood biomarkers Hepatic time to progression (hTTP) according to mRECIST and RECIST 1.1;Timepoint(s) of evaluation of this end point: PK Profile: Part A - pre-dose, and at 20, 60, and 90 minutes and at 2, 4, 8, 12, and 24 hours after start of the treatment. Thereafter, plasma samples will be obtained at 3, 7, 14, 21, 28 and 48 days. Objective response rate: 4 weeks, 3 and 6 months Disease control rate: 4 weeks, 3 and 6 months AFP Levels: Baseline to end of study Blood Biomarkers: Baseline to end of study | — |
Countries
France, Switzerland, United Kingdom
Contacts
Public ContactProject Manager
Prn Clinical Services
Outcome results
None listed