Efficacy Evaluation of TheraSphere in Patients With Inoperable Liver Cancer

Unresectable Hepatocellular Carcinoma Clinical Trial

— STOP-HCC  

Official title:

A Phase III Clinical Trial of Intra-arterial TheraSphere® in the Treatment of Patients With Unresectable Hepatocellular Carcinoma (HCC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01556490
• Other study ID #: TS-103
• Status: Completed
• Phase: N/A
• Start date: March 2012
• Est. completion date: April 30, 2022

Study information

• Verified date: August 2023
• Source: Boston Scientific Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 526
• Est. completion date: April 30, 2022
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 10?/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)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Unresectable Hepatocellular Carcinoma

Intervention

Device:
• TheraSphere
Yttrium 90 microspheres

Locations

Country	Name	City	State
Belgium	CUB Hôpital Erasme	Bruxelles
Belgium	CHU Liege	Liege
Canada	University of Alberta Hspital	Edmonton	Alberta
Canada	McGill University Health Centre / Royal Victoria Hospital	Montreal	Quebec
Canada	CHUM St. Luc	Montréal
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
France	Hôpital Jean Verdier	Bondy
France	CHU Estaing	Clermont-Ferrand
France	APHP Hôpital Henri Mondor	Creteil
France	CHU Dijon	Dijon
France	CHU de Grenoble	La Tronche
France	Centre Léon-Bérard	Lyon
France	CHU Lyon - Hopital de la Croix Rousse	Lyon
France	Hopital de la Timone CHU	Marseille
France	Hôpital Saint Eloi	Montpellier
France	CHU Hôtel-Dieu	Nantes
France	CHU de Nice	Nice
France	Hôpital Haut-Lévêque, CHU Bordeaux	Pessac Cedex
France	CHU de Poitiers	Poitiers
France	CHU Reims	Reims Cedex
France	Centre Eugene Marquis	Rennes Cedex
France	CHU Amiens Picardie - Hôpital Sud	Salouël
France	Hôpital de Hautepierre	Strasbourg
France	Hôpital Purpan	Toulouse
France	CHU Nancy	Vandoeuvre-les-Nancy
France	Hôpital Universitaire Paul Brousse	Villejuif
France	Institut Gustave Roussy	Villejuif Cedex
Germany	Universitätsklinikum Bonn	Bonn
Germany	Universitaetsklinikum Essen	Essen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Leipzig, Klinik für Diagnostische und Interventionelle Radiologie	Leipzig
Germany	Universitätsklinikum Tübingen, Diagnostische und Interventionelle Radiologie	Tübingen
Italy	Azienda Ospedaliero -Universitaria di Bologna	Bologna
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	St. Mary Hospital	Daegu
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Netherlands	AMC	Amsterdam
Netherlands	VUMC	Amsterdam
Netherlands	UMCG	Groningen
Netherlands	LUMC	Leiden
Netherlands	MUMC	Maastricht
Netherlands	Erasmus MC	Rotterdam
Singapore	National University Hospital	Singapore
Spain	Hospital Infanta Cristina	Badajoz
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	UDIAT Corporacio Parc Tauli	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital Virgen de las Nieves	Granada
Spain	Hospital Clínico San Carlos	Madrid
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	Hosptal Universitario Central de Asturias (nuevo HUCA)	Oviedo
Spain	Hospital Clínico Universitario	Salamanca
Spain	H. Virgen del Rocio	Sevilla
Spain	Hospital Universitario y Politecnico La Fe	Valencia
Spain	Hospital Clínico Universitario de Valladolid	Valladolid
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza
United Kingdom	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	Royal Liverpool University Hospital	Liverpool
United Kingdom	Imperial College London	London
United Kingdom	King's College Hospital;	London
United Kingdom	University College London Cancer Institute	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	Freeman Hospital	Newcastle upon Tyne
United Kingdom	Weston Park Hospital, Sheffield	Sheffield
United States	Montefiore Medical Center	Bronx	New York
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Miami Valley Hospital	Dayton	Ohio
United States	Wayne State Harper Hospital	Detroit	Michigan
United States	Northshore Hospital	Evanston	Illinois
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	University of Louisville	Louisville	Kentucky
United States	Weill Cornell Medical Center	New York	New York
United States	Sentra Norfolk General Hospital	Norfolk	Virginia
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Banner - University Medical Center Phoenix	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	St Marks Hospital	Salt Lake City	Utah
United States	Seattle Cancer Care Alliance/University of Washington Medical Center	Seattle	Washington
United States	H Lee Moffitt Cancer Center	Tampa	Florida
United States	Legacy Meridian Park Medical Center	Tualatin	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Boston Scientific Corporation	Biocompatibles UK Ltd

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Singapore,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) Results Are Based on the Modified Intent-to-treat (mITT)	Time from randomization until date of death due to any cause as reported by study site.	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
Primary	Overall Survival (OS) Per Protocol (PP) Population	Per Protocol = subset of the mITT population excluding patients with major protocol deviations which may affect the efficacy evaluation.	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	Time to Progression (TTP) From Time of Randomization Based on Investigator, According RECIST Criteria.	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.	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	Time to Untreatable Progression (TTUP) From the Time of Randomization Based One or More of the Following: Investigator Assessment According to RECIST Criteria	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.	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	Tumor Response	Objective Response Rate by investigator determination per RECIST 1.1	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

External Links

•   Trial-specific website