Clinical trial NCT01887717: Efficacy Evaluation of TheraSphere to Treat Inoperable Liver Cancer With Blockage of the Portal Vein
Official 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: hepatocellular carcinoma
portal vein thrombosis
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
Collaborators: name: Biocompatibles UK Ltd
First posted: 2013-06-27
Enrollment: 36
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: 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.

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

Primary outcomes:
measure: Overall Survival (OS) From Time of Randomization
timeFrame: Randomization up to participant's death (maximum time = up to Month 30)
Secondary outcomes:
measure: Time to Progression (TTP)
timeFrame: Randomization up to participant's death (maximum time = up to Month 30)
measure: Time to Worsening Portal Vein Thrombosis (PVT)
timeFrame: Baseline (Randomization) up to participant's death (maximum time = up to Month 30)
measure: Time to Symptomatic Progression (TTSP)
timeFrame: Randomization up to participant's death (maximum time = up to Month 30)
measure: Number of Participants With Tumor Response
timeFrame: Baseline up to participant's death (maximum time = up to Month 30)
measure: Change From Baseline in Quality of Life (QoL) as Assessed by the FACT-Hep Questionnaire
timeFrame: Baseline (Randomization), participant's death (maximum time = up to Month 30)
measure: Time to Deterioration QoL (TTDQoL)
timeFrame: Baseline (Randomization) up to participant's death (maximum time = up to Month 30)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE)
timeFrame: Randomization up to participant's death (maximum time = up to Month 30)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation, Div of Hematology/Oncology
state: Illinois
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Marseille
country: France
facility: Paoli-Calmettes Institute
city: Bergamo
country: Italy
facility: UO Radiologia, Ospedali Riuniti di Bergamo
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna
city: Cuneo
country: Italy
facility: ASO-Santa Croce e Carle di Cuneo
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Grande
city: Milano
country: Italy
facility: S.C Radiologia Interventistica, A.O.Ospedale Niguarda Ca Granda
city: Milano
country: Italy
facility: Fondazione Istituto Nazionale Tumori di Milano
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti "Villa Sofia-Cervello"
city: Pisa
country: Italy
facility: University of Pisa
city: Rome
country: Italy
facility: Policlinico A. Gemelli
city: Barcelona
country: Spain
facility: Hospital Clínic Barcelona. IDIBAPS. CIBEREHD. Liver Unit
city: Madrid
country: Spain
facility: Bulevar Sur s/n
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro, Gastroenterology & Hepatology Dept
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic la Fe
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
Study officials:
affiliation: Istituto Tumori Nazionale, Milan, Italy
name: Vincenzo Mazzaferro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University Chicago Illinois
name: Riad Salem, MD
role: PRINCIPAL_INVESTIGATOR
References: