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

NCT01887717 | Terminated Phase 3 Results DMC

• 2 other identifiers: TS-1042012-005375-14
• Study Type: interventional
• Target: 36
• Locations: 6 countries
• Sites: 19

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.

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; portal vein thrombosis

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) From Time of Randomization

  OS was calculated as the interval between the randomization date and the date of death for any cause, with censoring at the date of last contact for participants alive.

  Randomization up to participant's death (maximum time = up to Month 30)

Secondary Outcomes (7)

• Time to Progression (TTP)

  Randomization up to participant's death (maximum time = up to Month 30)

• Time to Worsening Portal Vein Thrombosis (PVT)

  Baseline (Randomization) up to participant's death (maximum time = up to Month 30)

• Time to Symptomatic Progression (TTSP)

  Randomization up to participant's death (maximum time = up to Month 30)

• Number of Participants With Tumor Response

  Baseline up to participant's death (maximum time = up to Month 30)

• Change From Baseline in Quality of Life (QoL) as Assessed by the FACT-Hep Questionnaire

  Baseline (Randomization), participant's death (maximum time = up to Month 30)

Study Arms (2)

TheraSphere

EXPERIMENTAL

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.

Device: TheraSphere®

Sorafenib

ACTIVE COMPARATOR

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.

Drug: Sorafenib

Interventions

TheraSphere® DEVICE

Intrahepatic treatment of advanced hepatocellular carcinoma

Also known as: yttrium-90 microspheres

TheraSphere

Sorafenib DRUG

Standard of care therapy for treatment of advanced hepatocellular carcinoma

Also known as: Nexavar®

Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Scientific Corporation: lead
• Biocompatibles UK Ltd: collaborator

Study Sites (19)

Northwestern Medical Faculty Foundation, Div of Hematology/Oncology

Chicago, Illinois, 60611, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Paoli-Calmettes Institute

Marseille, 13273, France

Location

UO Radiologia, Ospedali Riuniti di Bergamo

Bergamo, 24128, Italy

Location

Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138, Italy

Location

ASO-Santa Croce e Carle di Cuneo

Cuneo, 12100, Italy

Location

Fondazione IRCCS Ca Grande

Milan, 20122, Italy

Location

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

Milan, 20162, Italy

Location

Fondazione Istituto Nazionale Tumori di Milano

Milan, I-20133, Italy

Location

Azienda Ospedaliera Ospedali Riuniti "Villa Sofia-Cervello"

Palermo, 90147, Italy

Location

University of Pisa

Pisa, 56100, Italy

Location

Policlinico A. Gemelli

Rome, 8 - 00168, Italy

Location

Hospital Clínic Barcelona. IDIBAPS. CIBEREHD. Liver Unit

Barcelona, 08036, Spain

Location

Bulevar Sur s/n

Madrid, 28041, Spain

Location

Hospital Universitario Puerta de Hierro, Gastroenterology & Hepatology Dept

Madrid, 28222, Spain

Location

Hospital Universitari i Politecnic la Fe

Valencia, 46026, Spain

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2WB, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

On 23 May 2017, the Sponsor announced early termination of the study because fewer than half of the participants remained in follow-up resulting in to few participants for the study to be continued.

Results Point of Contact

• Title: Manager of Clinical Development
• Organization: BTG International Inc.

TheraSphereClinical@btgplc.com

613-801-1844

Study Officials

• Vincenzo Mazzaferro, MD

  Istituto Tumori Nazionale, Milan, Italy

  PRINCIPAL INVESTIGATOR

• Riad Salem, MD

  Northwestern University Chicago Illinois

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2013
• First Posted: June 27, 2013
• Study Start: February 27, 2014
• Primary Completion: May 23, 2017
• Study Completion: May 23, 2017
• Last Updated: April 21, 2021
• Results First Posted: October 29, 2019

Record last verified: 2021-04

Locations

US (2); BE (1); FR (1); IT (9); ES (4); GB (2)