Efficacy Evaluation of TheraSphere in Patients With Inoperable Liver Cancer
- Conditions
- Unresectable Hepatocellular Carcinoma
- Interventions
- Device: TheraSphere
- Registration Number
- NCT01556490
- Lead Sponsor
- Boston Scientific Corporation
- Brief Summary
The safety and effectiveness of TheraSphere will be evaluated in patients with unresectable hepatocellular carcinoma in whom treatment with standard-of-care sorafenib is planned. All patients receive the standard-of-care sorafenib with or without the addition of TheraSphere.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 526
- Signed informed consent prior to any study-related evaluation
- Male or female patients over 18 years of age
- Unresectable HCC confirmed by histology or by non-invasive AASLD criteria
- Measurable disease defined as at least one uni-dimensional measurable lesion by CT or MRI according to RECIST 1.1
- Child Pugh score ≤ 7 points
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤ 1
- Life expectancy of 12 weeks or more
- Eligible to receive standard-of-care sorafenib
- Platelet count of > 50 x 10⁹/L or > 50% prothrombin activity
- Hemoglobin ≥ 8.5 g/dL
- Bilirubin ≤ 2.5 mg/dL
- Alanine transaminase (ALT) and Aspartate Aminotransferase (AST)< 5 X upper limit of normal
- Amylase or lipase ≤ 2X upper limit of normal
- Serum creatinine ≤ 1.5 X upper limit of normal
- International normalized ratio (INR) < 2.0
- Main portal vein thrombosis
- Eligible for curative treatment (ablation or transplantation)
- History of previous or concurrent cancer other than HCC unless treated curatively 5 or more years prior to entry
- Confirmed presence of extra-hepatic disease except lung nodules and mesenteric or portal lymph nodes ≤ 2.0 cm each
- Risk of hepatic or renal failure
- Tumor replacement ≥ 70% of total liver volume based on visual estimation by investigator OR tumor replacement ≥ 50% of total liver volume in the presence of albumin <3 mg/dL
- History of severe allergy or intolerance to contrast agents, narcotics sedatives or atropine that cannot be managed medically
- Contraindications to angiography and selective visceral catheterization.
- History of organ allograft
- Known contraindications to sorafenib including allergic reaction, pill-swallowing difficulty, evidence of severe or systemic diseases, uncontrolled severe hypertension or history of cardiac arrhythmias, congestive heart failure . New York Heart Association class 2, myocardial infarct within 6 months, prolonged QT/QTc >450ms, evidence of torsades de pointe, 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, metastatic brain disease, renal failure requiring dialysis
- Taking any of the following: Rifampicin, St. John's Wort, phenytoin, carbamazepine, phenobarbital, dexamethasone
- Taking any other systemic anticancer agent (docetaxel, doxorubicin, irinotecan)
- Taking any substrate agents for Cytochrome P450 (CYP) 2B6 (bupropion, cyclophosphamide, efavirenz, ifosfamide, methadone, paclitaxel, amodiaquine, repaglinide)
- Taking any UDP-glucuronosyltransferase (UGT) 1A1 and UGT 1A9 substrates (e.g. irinotecan)
- Taking P-Gp substrates (e.g. Digoxin)
- Prior liver resection must have taken ≥2 months prior to randomization
- Treatment with other locoregional therapies (other than study treatment) has not been planned for the duration of the clinical study period
- Prior external beam radiation treatment to the chest, liver or abdomen
- Prior yttrium-90 microsphere treatment to the liver
- Prior treatment with transarterial chemoembolization (TACE) or bland embolization must have occurred >2 months prior to randomization and must have been applied to a treatment field and/or lobe not targeted for treatment under this protocol. For patients with tumor progression in the treatment field and /or lobe previously treated with TACE, vessels feeding the tumor(s) must be assessed for adequate blood flow using angiography (cone beam computerized tomography (CBCT) strongly recommended), and TACE or bland embolization must have been applied >6 months prior to randomization.
- Anti-cancer therapy or any treatment with an investigational agent within 30 days prior to randomization
- Adverse effects due to prior therapy unresolved at randomization
- Prior systemic treatment for the treatment of HCC, including sorafenib given for more than 4 weeks during the 2 previous months prior to randomization, no prior sorafenib related toxicity
- Evidence of pulmonary insufficiency or inadequately treated moderate grade or severe/very severe grade chronic obstructive pulmonary disease
- Intervention for, or compromise of, the Ampulla of Vater
- Clinically evident ascites (trace ascites on imaging is acceptable)
- Pregnancy or breast feeding
- Women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to randomization
- Disease or condition that would preclude safe use of TheraSphere, including concurrent dialysis treatment, or unresolved serious infections. Patients infected with HIV can be considered, however, they must be well managed and well controlled with undetectable viral load
- Participation in concurrent clinical trials evaluating treatment intervention(s)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment group TheraSphere Standard-of-care sorafenib plus TheraSphere
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Results Are Based on the Modified Intent-to-treat (mITT) From time of randomization up to date of death or last date known to be alive (data cut-off 30Apr2022), an average of 16.3 months Time from randomization until date of death due to any cause as reported by study site.
Overall Survival (OS) Per Protocol (PP) Population From time of randomization up to date of death or last date known to be alive (data cut-off 30Apr2022), an average of 16.3 months Per Protocol = subset of the mITT population excluding patients with major protocol deviations which may affect the efficacy evaluation.
- Secondary Outcome Measures
Name Time Method Time to Untreatable Progression (TTUP) From the Time of Randomization Based One or More of the Following: Investigator Assessment According to RECIST Criteria From time of randomization up to date of death or last date known to be alive (data cut-off 30Apr2022), an average of 16.3 months Time to progression (TTP) will be calculated as the interval between the randomization date and the date of first disease progression, including the appearance of new lesion(s) and death for any cause or of last contact for patients alive.
Tumor Response From time of randomization up to date of death or last date known to be alive (data cut-off 30Apr2022), an average of 16.3 months Objective Response Rate by investigator determination per RECIST 1.1
Time to Progression (TTP) From Time of Randomization Based on Investigator, According RECIST Criteria. From time of randomization up to date of death or last date known to be alive (data cut-off 30Apr2022), an average of 16.3 months Time to progression (TTP) will be calculated as the interval between the randomization date and the date of first disease progression, including the appearance of new lesion(s) (per RECIST 1.1) and death for any cause or of last contact for patients alive.
Trial Locations
- Locations (93)
CHU Nancy
🇫🇷Vandoeuvre-les-Nancy, France
LUMC
🇳🇱Leiden, Netherlands
MUMC
🇳🇱Maastricht, Netherlands
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Hospital Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Servicio de Radiología, Hospital Universitario Virgen de la Arrixaca.
🇪🇸Murcia, Spain
Hospital Clínico Universitario
🇪🇸Salamanca, Spain
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
CHU Liege
🇧🇪Liege, Belgium
University of Alberta Hspital
🇨🇦Edmonton, Alberta, Canada
Legacy Meridian Park Medical Center
🇺🇸Tualatin, Oregon, United States
McGill University Health Centre / Royal Victoria Hospital
🇨🇦Montreal, Quebec, Canada
CHU Hôtel-Dieu
🇫🇷Nantes, France
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Northshore Hospital
🇺🇸Evanston, Illinois, United States
Weill Cornell Medical Center
🇺🇸New York, New York, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Sentra Norfolk General Hospital
🇺🇸Norfolk, Virginia, United States
Seattle Cancer Care Alliance/University of Washington Medical Center
🇺🇸Seattle, Washington, United States
CUB Hôpital Erasme
🇧🇪Bruxelles, Belgium
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
CHUM St. Luc
🇨🇦Montréal, Canada
Hôpital Jean Verdier
🇫🇷Bondy, France
CHU Estaing
🇫🇷Clermont-Ferrand, France
APHP Hôpital Henri Mondor
🇫🇷Creteil, France
CHU de Grenoble
🇫🇷La Tronche, France
Centre Léon-Bérard
🇫🇷Lyon, France
CHU Dijon
🇫🇷Dijon, France
CHU Lyon - Hopital de la Croix Rousse
🇫🇷Lyon, France
Hôpital Saint Eloi
🇫🇷Montpellier, France
CHU de Nice
🇫🇷Nice, France
Hopital de la Timone CHU
🇫🇷Marseille, France
Hôpital Haut-Lévêque, CHU Bordeaux
🇫🇷Pessac Cedex, France
CHU Reims
🇫🇷Reims Cedex, France
CHU de Poitiers
🇫🇷Poitiers, France
Centre Eugene Marquis
🇫🇷Rennes Cedex, France
CHU Amiens Picardie - Hôpital Sud
🇫🇷Salouël, France
Hôpital de Hautepierre
🇫🇷Strasbourg, France
Hôpital Purpan
🇫🇷Toulouse, France
Hôpital Universitaire Paul Brousse
🇫🇷Villejuif, France
Institut Gustave Roussy
🇫🇷Villejuif Cedex, France
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Universitätsklinikum Leipzig, Klinik für Diagnostische und Interventionelle Radiologie
🇩🇪Leipzig, Germany
Azienda Ospedaliero -Universitaria di Bologna
🇮🇹Bologna, Italy
Universitätsklinikum Tübingen, Diagnostische und Interventionelle Radiologie
🇩🇪Tübingen, Germany
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
St. Mary Hospital
🇰🇷Daegu, Korea, Republic of
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
VUMC
🇳🇱Amsterdam, Netherlands
AMC
🇳🇱Amsterdam, Netherlands
Severance Hospital
🇰🇷Seoul, Korea, Republic of
UMCG
🇳🇱Groningen, Netherlands
National University Hospital
🇸🇬Singapore, Singapore
UDIAT Corporacio Parc Tauli
🇪🇸Barcelona, Spain
Erasmus MC
🇳🇱Rotterdam, Netherlands
Hospital Infanta Cristina
🇪🇸Badajoz, Spain
Hospital Clinic i Provincial
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Virgen de las Nieves
🇪🇸Granada, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
H. Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario y Politecnico La Fe
🇪🇸Valencia, Spain
Hosptal Universitario Central de Asturias (nuevo HUCA)
🇪🇸Oviedo, Spain
Hospital Clínico Universitario de Valladolid
🇪🇸Valladolid, Spain
Hospital Clínico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
New Queen Elizabeth Hospital Birmingham
🇬🇧Birmingham, United Kingdom
Addenbrooks Hospital
🇬🇧Cambridge, United Kingdom
Edinburgh Cancer Centre
🇬🇧Edinburgh, United Kingdom
Royal Surrey Country Hospital
🇬🇧Guildford, United Kingdom
University College London Cancer Institute
🇬🇧London, United Kingdom
King's College Hospital;
🇬🇧London, United Kingdom
Christie Hospital
🇬🇧Manchester, United Kingdom
Imperial College London
🇬🇧London, United Kingdom
Freeman Hospital
🇬🇧Newcastle upon Tyne, United Kingdom
Weston Park Hospital, Sheffield
🇬🇧Sheffield, United Kingdom
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Banner - University Medical Center Phoenix
🇺🇸Phoenix, Arizona, United States
H Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
Wayne State Harper Hospital
🇺🇸Detroit, Michigan, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
St Marks Hospital
🇺🇸Salt Lake City, Utah, United States
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom