Clinical trial NCT01556490: Efficacy Evaluation of TheraSphere in Patients With Inoperable Liver Cancer
Official title: A Phase III Clinical Trial of Intra-arterial TheraSphere® in the Treatment of Patients With Unresectable Hepatocellular Carcinoma (HCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Unresectable Hepatocellular Carcinoma
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
Collaborators: name: Biocompatibles UK Ltd
First posted: 2012-03-16
Enrollment: 526
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Overall Survival (OS) Results Are Based on the Modified Intent-to-treat (mITT)
timeFrame: 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
measure: Overall Survival (OS) Per Protocol (PP) Population
timeFrame: 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
Secondary outcomes:
measure: Time to Progression (TTP) From Time of Randomization Based on Investigator, According RECIST Criteria.
timeFrame: 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
measure: Time to Untreatable Progression (TTUP) From the Time of Randomization Based One or More of the Following: Investigator Assessment According to RECIST Criteria
timeFrame: 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
measure: Tumor Response
timeFrame: 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
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner - University Medical Center Phoenix
state: Arizona
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Evanston
country: United States
facility: Northshore Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Detroit
country: United States
facility: Wayne State Harper Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Tualatin
country: United States
facility: Legacy Meridian Park Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Salt Lake City
country: United States
facility: St Marks Hospital
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Norfolk
country: United States
facility: Sentra Norfolk General Hospital
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance/University of Washington Medical Center
state: Washington
city: Bruxelles
country: Belgium
facility: CUB Hôpital Erasme
city: Liege
country: Belgium
facility: CHU Liege
city: Edmonton
country: Canada
facility: University of Alberta Hspital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre / Royal Victoria Hospital
state: Quebec
city: Montréal
country: Canada
facility: CHUM St. Luc
city: Bondy
country: France
facility: Hôpital Jean Verdier
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Creteil
country: France
facility: APHP Hôpital Henri Mondor
city: Dijon
country: France
facility: CHU Dijon
city: La Tronche
country: France
facility: CHU de Grenoble
city: Lyon
country: France
facility: CHU Lyon - Hopital de la Croix Rousse
city: Lyon
country: France
facility: Centre Léon-Bérard
city: Marseille
country: France
facility: Hopital de la Timone CHU
city: Montpellier
country: France
facility: Hôpital Saint Eloi
city: Nantes
country: France
facility: CHU Hôtel-Dieu
city: Nice
country: France
facility: CHU de Nice
city: Pessac Cedex
country: France
facility: Hôpital Haut-Lévêque, CHU Bordeaux
city: Poitiers
country: France
facility: CHU de Poitiers
city: Reims Cedex
country: France
facility: CHU Reims
city: Rennes Cedex
country: France
facility: Centre Eugene Marquis
city: Salouël
country: France
facility: CHU Amiens Picardie - Hôpital Sud
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
city: Toulouse
country: France
facility: Hôpital Purpan
city: Vandoeuvre-les-Nancy
country: France
facility: CHU Nancy
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Villejuif
country: France
facility: Hôpital Universitaire Paul Brousse
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Klinik für Diagnostische und Interventionelle Radiologie
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Diagnostische und Interventionelle Radiologie
city: Bologna
country: Italy
facility: Azienda Ospedaliero -Universitaria di Bologna
city: Daegu
country: Korea, Republic of
facility: St. Mary Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Amsterdam
country: Netherlands
facility: VUMC
city: Amsterdam
country: Netherlands
facility: AMC
city: Groningen
country: Netherlands
facility: UMCG
city: Leiden
country: Netherlands
facility: LUMC
city: Maastricht
country: Netherlands
facility: MUMC
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Singapore
country: Singapore
facility: National University Hospital
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: UDIAT Corporacio Parc Tauli
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Granada
country: Spain
facility: Hospital Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Murcia
country: Spain
facility: Servicio de Radiología, Hospital Universitario Virgen de la Arrixaca.
city: Oviedo
country: Spain
facility: Hosptal Universitario Central de Asturias (nuevo HUCA)
city: Salamanca
country: Spain
facility: Hospital Clínico Universitario
city: Sevilla
country: Spain
facility: H. Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
city: Birmingham
country: United Kingdom
facility: New Queen Elizabeth Hospital Birmingham
city: Cambridge
country: United Kingdom
facility: Addenbrooks Hospital
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre
city: Guildford
country: United Kingdom
facility: Royal Surrey Country Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: University College London Cancer Institute
city: London
country: United Kingdom
facility: King's College Hospital;
city: London
country: United Kingdom
facility: Imperial College London
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital, Sheffield
Study officials:
affiliation: Dept of Radiology Northwestern University
name: Riad Salem, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chauhan N, Bukovcan J, Boucher E, Cosgrove D, Edeline J, Hamilton B, Kulik L, Master F, Salem R. Intra-Arterial TheraSphere Yttrium-90 Glass Microspheres in the Treatment of Patients With Unresectable Hepatocellular Carcinoma: Protocol for the STOP-HCC Phase 3 Randomized Controlled Trial. JMIR Res Protoc. 2018 Aug 15;7(8):e11234. doi: 10.2196/11234.