Efficacy Evaluation of TheraSphere to Treat Inoperable Liver Cancer With Blockage of the Portal Vein

NCT ID: NCT01887717

Last Updated: 2021-04-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-27
• Study Completion Date: 2017-05-23

Brief Summary

This is a two-arm, open-label, prospective, multi-center, randomized, active-controlled clinical trial to assess efficacy and safety of TheraSphere in comparison to standard of care therapy (sorafenib) in the treatment of participants with inoperable liver cancer and blockage of the portal vein.

Detailed Description

The objective of this Phase III, prospective randomized trial is to determine whether TheraSphere provides a meaningful benefit in survival in comparison with the standard of care (sorafenib) in participants with good hepatic function and advanced hepatocellular carcinoma (HCC) associated with portal vein thrombosis (PVT).

This is an open-label prospective, multi-center, randomized, controlled clinical trial that will evaluate the use of TheraSphere compared to standard-of-care sorafenib alone.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TheraSphere

Participants will receive TheraSphere at a dose consistent with the approved product label to the treated lobe of the liver. TheraSphere will be administered through the hepatic artery. The target dose will be 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% will be permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere will be permitted if a treatable progression is detected during follow-up evaluations. Any re-treatment will take place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants can receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations will be permitted.

Group Type: EXPERIMENTAL

TheraSphere®

Intervention Type: DEVICE

Intrahepatic treatment of advanced hepatocellular carcinoma

Sorafenib

Participants will receive sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment is to continue until the participant is no longer clinically benefiting from therapy or until unacceptable toxicity occurs. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity will be allowed.

Group Type: ACTIVE_COMPARATOR

Sorafenib

Intervention Type: DRUG

Standard of care therapy for treatment of advanced hepatocellular carcinoma

Interventions

TheraSphere®

Intrahepatic treatment of advanced hepatocellular carcinoma

Intervention Type: DEVICE

Sorafenib

Standard of care therapy for treatment of advanced hepatocellular carcinoma

Intervention Type: DRUG

Other Intervention Names

yttrium-90 microspheres; Nexavar®

Eligibility Criteria

Inclusion Criteria

• Participants over 18 years of age, regardless of race or gender
• Advanced unresectable hepatocellular carcinoma with branch portal vein thrombosis (confirmed by non-invasive criteria European Association for the Study of the Liver [EASL]/American Association for the Study of Liver Diseases [AASLD], mandatory by histology in non-cirrhotic participants); can be naive or recurrent HCC after curative treatment ( >6 months before randomization)
• Unilobar disease
• Child Pugh A
• Tumor volume ≤70% of liver volume (determined by visual estimation)
• At least one uni-dimensional HCC target lesion assessable by computed tomography (CT) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Platelets ≥ 50*10^3/microliter (µL)
• White blood cell (WBC) ≥1.5*10^3/microliter (µL)
• Aspartate transaminase (AST)/ alanine aminotransferase (ALT) ≤5 times upper limit of normal
• Creatinine ≤2.0 mg/deciliter (dL)
• Life expectancy >3 months
• Signed informed consent

Exclusion Criteria

• Confirmed extra hepatic metastases. Participants with indeterminate hepatic hilar lymph nodes up to 2.5 centimeters (cm) in greatest dimension, or with indeterminate lung nodules (single lesion between 1-1.5 cm, or multiple smaller lesions with a total diameter of ≤2 cm) may be included if metastatic disease is deemed unlikely
• Known contraindication to standard-of-care sorafenib including allergic reaction, pill swallowing difficulty, uncontrolled hypertension or history of cardiac disease, significant GI bleed within 30 days, and renal failure including dialysis
• Evidence of hepatic vein invasion or caval thrombosis
• Evidence of chronic obstructive pulmonary disease
• Indication for any possible curative treatment after multidisciplinary assessment (surgery, ablation, transplantation)
• Previous treatment with sorafenib for more than 4 weeks during the previous 2 months; prior sorafenib-related toxicity
• Initiation of anti-tumor therapy including chemotherapy or investigational drug treatment within 30 days before beginning study
• Prior transarterial chemoembolization (TACE) <6 months prior to screening phase in case of participants progressing from an intermediate to an advanced stage due to occurrence of PVT
• On a transplant list
• History of organ allograft
• Contraindications to angiography or selective visceral catheterization
• History of severe allergy or intolerance to contrast agents, narcotics, sedatives, or atropine that cannot be managed medically
• Prior external beam radiation therapy to the liver
• Evidence of continuing adverse effect of prior therapy
• Active gastrointestinal (GI) bleeding and any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents
• Evidence of any disease or condition that would place the participant at undue risk and preclude safe use of TheraSphere treatment
• Females of child-bearing potential must have a negative serum test
• No participation in concurrent clinical trials

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biocompatibles UK Ltd

INDUSTRY

Sponsor Role: collaborator

Boston Scientific Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vincenzo Mazzaferro, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Tumori Nazionale, Milan, Italy

Riad Salem, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University Chicago Illinois

Locations

Northwestern Medical Faculty Foundation, Div of Hematology/Oncology

Chicago, Illinois, United States

Mount Sinai School of Medicine

New York, New York, United States

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Paoli-Calmettes Institute

Marseille, , France

UO Radiologia, Ospedali Riuniti di Bergamo

Bergamo, , Italy

Azienda Ospedaliero-Universitaria di Bologna

Bologna, , Italy

ASO-Santa Croce e Carle di Cuneo

Cuneo, , Italy

Fondazione IRCCS Ca Grande

Milan, , Italy

S.C Radiologia Interventistica, A.O.Ospedale Niguarda Ca Granda

Milan, , Italy

Fondazione Istituto Nazionale Tumori di Milano

Milan, , Italy

Azienda Ospedaliera Ospedali Riuniti "Villa Sofia-Cervello"

Palermo, , Italy

University of Pisa

Pisa, , Italy

Policlinico A. Gemelli

Rome, , Italy

Hospital Clínic Barcelona. IDIBAPS. CIBEREHD. Liver Unit

Barcelona, , Spain

Bulevar Sur s/n

Madrid, , Spain

Hospital Universitario Puerta de Hierro, Gastroenterology & Hepatology Dept

Madrid, , Spain

Hospital Universitari i Politecnic la Fe

Valencia, , Spain

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Royal Free London NHS Foundation Trust

London, , United Kingdom

Countries

United States; Belgium; France; Italy; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2012-005375-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TS-104

Identifier Type: -

Identifier Source: org_study_id