A prospective randomized clinical trial with the medical device Therasphere versus the drug sorafenib for the treatment of liver cancer (HCC) with a clot in the major liver (Portal Vein Thrombosis - PVT)

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2012-005375-14-GB
• Date of registration: 23/05/2013
• Prospective Registration: Yes
• Primary sponsor: Biocompatibles UK Ltd
• Public title: A prospective randomized clinical trial with the medical device Therasphere versus the drug sorafenib for the treatment of liver cancer (HCC) with a clot in the major liver (Portal Vein Thrombosis - PVT)
• Scientific title: A prospective randomized clinical trial on 90Yttrium trans-arterial radio-Embolization (Therasphere) vs. standard of care (sorafenib) for the treatment of advanced Hepatocellular carcinoma (HCC) with Portal Vein Thrombosis (PVT) - YES-P
• Date of first enrolment: 29/08/2013
• Target sample size: 318
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005375-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Medical device trial with the IMP sorafenib being the comparator Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Hong Kong, Spain, United Kingdom, United States

Contacts

• Name: Project management
• Affiliation: Theorem Clinical Research

• Name: Project management
• Affiliation: Theorem Clinical Research

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients over 18 years of age, regardless of race or gender
2. Advanced stage HCC confirmed by histology (mandatory in non cirrhotic patients) or non-invasive criteria (EASL/AASLD) with branch PVT.
o Either naïve or recurrent HCC after curative treatment (minimum 3 months from curative treatment - minor resection or local ablation) is acceptable.
o Branch PVT classified as Type I, Type II or Type IIIa (see Section 9.2.5).
3. Unilobar disease as defined in Section 8.1.
4. Tumor volume = 70% of liver volume (determined by visual estimation)
5. Child-Pugh A
6. At least one uni-dimensional HCC target lesion assessable according to the RECIST v1.1 criteria by CT-scan or MRI
7. No confirmed extrahepatic metastases. Patients with indeterminate hepatic hilar lymph nodes up to 2.5 cm in greatest dimension, or with indeterminate lung nodules (single lesion between 1-1.5cm, or multiple smaller lesions with a total diameter = 2 cm) may be included if metastatic disease is deemed unlikely
8. No known contraindications to standard-of-care sorafenib including allergic reaction, pill swallowing difficulty, uncontrolled hypertension or history of cardiac disease (according to sorafenib package insert and country-specific policies, may include evidence of severe or uncontrolled systemic diseases, cardiac arrhythmias (requiring anti-arrhythmic therapy or pace maker), congestive cardiac failure >New York Heart Association class 2, myocardial infarct within 6 months, prolonged QT/QTc >450ms), or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial , significant GI bleed within 30 days, renal failure requiring dialysis
9. No evidence of hepatic vein invasion or caval thrombosis
10. Cancer-related symptoms within the ECOG 0-1 category
11. PLT = 50 x103/µL
12. WBC = 1.5 x103/µL
13. AST/ALT = 5 times the upper limit of normal (U/L)
14. Creatinine = 2.0 mg /dL
15. No evidence of pulmonary insufficiency or clinically evident chronic obstructive pulmonary disease.
16. No indication for any possible curative treatment after multidisciplinary assessment (surgery, ablation, transplantation)
17. No previous treatment with Sorafenib for more than 4 weeks during the 2 previous months; no prior sorafenib-related toxicity at any dose and/or duration defined as documented sorafenib-related grade 3 or 4 adverse events that led to sorafenib discontinuation
18. No initiation of any other anti-tumor therapy including chemotherapy, radioembolization (maximum lung shunt of 20% for prior radioembolization) or investigational drug treatment within 30 days before the beginning of the study
19. In case of patients progressing from an intermediate to an advance stage because of occurrence of PVT, enrolment is allowed if previous conventional or drug eluting TACE was performed at least 3 months prior to screening phase
20. Patients cannot be on a liver transplantation list
21. No history of organ allograft
22. No contraindication to angiography or selective visceral catheterization
23. No history of severe allergy or intolerance to contrast agents, narcotics, sedatives or atropine that cannot be managed medically
24. No previous external beam radiation treatment to the liver
25. No evidence of continuing adverse effect of prior therapy
26. No active GI bleeding and any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g., cl
Exclusion criteria:
Not applicable


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Advanced Hepatocellular Carcinoma (HCC) with Portal Vein Thrombosis (PVT)
MedDRA version: 18.0 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 100000004864
MedDRA version: 18.0 Level: PT Classification code 10036206 Term: Portal vein thrombosis System Organ Class: 10019805 - Hepatobiliary disorders

Intervention(s)

Trade Name: Nexavar
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SORAFENIB TOSYLATE
CAS Number: 475207-59-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: D0 until patient dies

Secondary Objective: Not applicable

Main Objective: Assess efficacy and safety of TheraSphere in comparison to standard of care therapy (sorafenib) in the treatment of patients with portal vein thrombosis associated with unresectable hepatocellular carcinoma.

Primary end point(s): Overall Survival

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: • Time to progression (TTP): D0, W4, W8, W12, W16, W20, W24, WQ8
• Time to worsening of PVT: D0, W8, W16, W24, WQ8
• Time to symptomatic progression (TTSP): D0 until ECOG performance status =2
• Tumor response: D-14 to 0, W4, W8, W12, W16, W20, W24, WQ8
• Patient reported outcome: D-14 to 0, W4, W8, W12, W16, W20, W24, WQ8
• Adverse events: D-14 to 0, W2, W4, W8, W12, W16, W20, W24, WQ8

Secondary end point(s): • Time to progression (TTP) based on investigator assessment according to RECIST v 1.1, modified RECIST and EASL response criteria
• Time to worsening of PVT
• Time to symptomatic progression (TTSP)
• Tumor response according to RECIST v 1.1, modified RECIST and EASL response criteria based on investigator evaluations
• Patient reported outcome (PRO) as assessed by the Functional Assessment of
Cancer Therapy – Hepatobiliary Questionnaire (FACT-Hep) questionnaire
• Adverse events

Secondary ID(s)

TS-104

2012-005375-14-BE

NCT01887717

Source(s) of Monetary Support

Biocompatibles UK Ltd