Study of Sorafenib and Transarterial Chemoembolization (TACE) to Treat Hepatocellular Carcinoma

NCT00844883 | Completed Phase 2 Results DMC

• 1 other identifier: J08110
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study will combine two therapies to treat patients with unresectable hepatocellular carcinoma; sorafenib, and drug eluting beads delivered intra-arterially. The purpose of the study is to establish the safety and the effectiveness of the combination therapy. The investigators hypothesize that the combination of the two therapies will not result in greater toxicities to patients than that expected for either therapy given alone.

Conditions

Hepatocellular Carcinoma; Hepatoma

Keywords

primary liver cancer; sorafenib; Nexavar; doxorubicin; drug eluting beads; transarterial chemoembolization

Outcome Measures

Primary Outcomes (2)

• Safety Will be Assessed by Grading Toxicities Reported at Intervals Throughout the Study. Higher Grade Toxicities Will be Assessed for Their Degree of Relatedness to the Study Treatment.

  Treatment toxicities assessed by CTCAE v3.0 were stratified by cycle - patients on Cycle 1, and patients on Cycles 2-5 or more. 50 patients were reviewed for toxicities for Cycle 1, and all 50 patients experienced at least one adverse event during this time period.

  6 weeks (Cycle 1)

• Safety Will be Assessed by Grading Toxicities Reported at Intervals Throughout the Study. Higher Grade Toxicities Will be Assessed for Their Degree of Relatedness to the Study Treatment.

  Treatment toxicities assessed by CTCAE v3.0 were stratified by cycle - patients on Cycle 1, and patients on Cycles 2-5 or more.

  2 years (Cycles 2-5+)

Secondary Outcomes (5)

• Efficacy Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) to Determine Response and Disease Control Rate

  6 months

• Efficacy Assessed by European Association for the Study of the Liver (EASL) Criteria to Determine Response and Disease Control Rate

  6 months

• Efficacy - Median TTP After Combination Treatment With Sorafenib and TACE

  3 years

• Efficacy - Overall Survival (OS) After Combination Treatment With Sorafenib and TACE

  3 years

• Efficacy - Factors Associated With Overall Survival (OS) After Combination Treatment With Sorafenib and TACE

  3 years

Other Outcomes (3)

• Estimated Percentage of Participants Surviving After One Year

  1 year

• Estimated Percentage of Participants Surviving After Three Year

  3 years

• Median Overall Survival OS Stratified by BCLC Criteria

  up to 4 years

Study Arms (1)

sorafenib and drug eluting beads

EXPERIMENTAL

single arm

Drug: sorafenib; Procedure: LC Bead-TACE

Interventions

sorafenib DRUG

sorafenib: given 400 mg twice per day for as long as it is beneficial

Also known as: sorafenib (Nexavar)

sorafenib and drug eluting beads

LC Bead-TACE PROCEDURE

LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period

Also known as: LC Beads manufactured by Biocompatibles

sorafenib and drug eluting beads

Eligibility Criteria

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

You may qualify if:

• Unresectable hepatocellular carcinoma (HCC) patients with liver-predominant disease as described in section 5.1, or patients with hepatocellular carcinoma who refuse surgery. No more than 30% of the cohort should have macrovascular invasion and/or asymptomatic extrahepatic disease. Multifocal HCC is acceptable, no diffuse HCC.
• Age \> 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Childs class of A or B (up to 7) (see Table 5.0)
• Adequate end-organ function as manifested by:
• Absolute neutrophil count of \> 1500/mm3 and platelets \> 50,000/mm3
• Creatinine ≤ 2.0
• Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) \< 5 x upper limit of normal (ULN)
• Total bilirubin of ≤ 3
• Albumin \> 2.0
• International normalized ratio (INR) \< 2.0
• Leukocyte count \>3000 cells/mm3
• Amylase and lipase ≤ 1.5 the upper limit of normal
• Patients who have received previous hepatic surgery , radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), or cryoablation are eligible if target lesion(s) have not been treated and local therapy completed \> 6 weeks prior to entry.
• Left ventricular ejection fraction ≥ 45%

You may not qualify if:

• Patients unable to swallow oral medications
• Prior embolization, systemic or radiation therapy for HCC (liver)
• Tumor burden in the liver exceeding 70%.
• Complete occlusion of the entire portal venous system
• Ascites refractory to diuretic therapy (minimal or trace on imaging is acceptable)
• Previous or concurrent cancer that is distinct in primary site or histology from HCC, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, and T1). Any cancer curatively treated \> 3 years prior is permitted.
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
• History of bleeding within the past 4 weeks (unless deemed by PI as clinically insignificant, for ex., a brief episode of epistaxis)
• Any contraindication to doxorubicin administration
• Evidence of severe or uncontrolled systemic diseases,
• Congestive cardiac failure \> New York Heart Association (NYHA) class 2, myocardial ischemia within 6 months, active coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, unstable angina, or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• History of stroke or transient ischemic attack within 6 months prior to study enrollment
• Inadequately controlled hypertension (defined as systolic blood pressure of 150/100 mmHg on antihypertensive medications) (patients with treated hypertension are eligible)
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection, peripheral vascular disease)

Sponsors & Collaborators

• Yale University: lead
• Bayer: collaborator
• Biocompatibles UK Ltd: collaborator

Study Sites (1)

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

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

Results Point of Contact

• Title: Jean-Francois Geschwind, MD
• Organization: Yale University

jeff.geschwind@yale.edu

203-785-5865

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2009
• First Posted: February 16, 2009
• Study Start: February 1, 2009
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: November 11, 2021
• Results First Posted: August 28, 2017

Record last verified: 2021-10

Locations

US (1)