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An Open-label, Randomized Phase 3 Study of the Efficacy and Tolerability of Linifanib (ABT-869) versus Sorafenib in Subjects with Advanced Hepatocellular Carcinoma (HCC) - ND

Conditions
Advanced Hepatocellular Carcinoma (HCC).
MedDRA version: 9.1Level: LLTClassification code 10019828
MedDRA version: 9.1Level: LLTClassification code 10019829
Registration Number
EUCTR2009-013435-38-IT
Lead Sponsor
Abbott GmBH & Co.KG
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
900
Inclusion Criteria

Each subject must fulfill all of the following criteria within 21 days prior to the first day of therapy. Subject must be  18 years of age. Subject must be diagnosed with unresectable or metastatic HCC defined by: o Histologic or cytologic diagnosis OR o European Association for the Study of Liver Criteria Radiological criteria: two coincident imaging techniques (Four techniques considered: ultrasound, spiral computed tomography (CT), magnetic resonance imaging (MRI) and angiography) Focal lesion > 2 cm with arterial hypervascularization Combined criteria: one imaging technique associated with AFP (alpha fetoprotein) > 400 ng/mL Subjects must have a measurable lesion by RECIST version 1.1 on CT scan in at least one site which has not received prior radiotherapy. Subjects must show signs of progression (i.e., new lesion per RECIST version 1.1) if prior liver-directed therapy was received. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 1. Subject must have the following laboratory values: o Total Bilirubin  3.0 mg/dL or equivalent o AST/ALT  5  ULN o PTT  1.5  ULN and INR < 1.5 o ANC  1.0  109/L o Platelet count  50  109/L if splenomegaly; if splenomegaly is not present, platelet count  75  109/L o Creatinine  1.5  ULN o Serum albumin  2.8 g/dL o PT  6 seconds prolonged Women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for 90 days following completion of therapy. Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to initiation of treatment and/or post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent, approved by an Independent Ethic Committee (IEC)/Institutional Review Board (IRB) prior to the initiation of any screening or study-specific procedures, and in the opinion of the Study Investigator with agreement by the subject, currently no other treatment options exist that will provide benefit to the subject and/or the subject is willing to receive (e.g., transcatheter arterial chemoembolization).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subject has received prior systemic (administered intravenously or orally rather than locoregionally) treatment for HCC. Subject has Child-Pugh grade Class B or C hepatic impairment. Subject has received prior local therapy (including liver-directed therapy) within 4 weeks prior to study drug administration. Local therapies include but are not limited to: surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation. In addition, subject has not recovered to  Grade 1 clinically significant adverse effects/toxicities of previous therapy. Subject has untreated brain or meningeal metastases. CT scans are not required to rule out brain or meningeal metastases unless there is a clinical suspicion of central nervous system disease. Subjects with treated brain metastases that are radiographically or clinically stable (for at least 4 weeks after therapy) and have no evidence of cavitation or hemorrhage in the brain lesion, are eligible provided that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to Study Day 1). Subject has previous or concurrent cancer that is distinct in primary site or histology from HCC except cervical carcinoma in situ, non-melanoma carcinoma of the skin or in situ carcinoma of the bladder. Any cancer curatively treated greater than 3 years prior to entry is permitted. The subject has proteinuria defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade > 1 at baseline as measured by a urine dipstick (2+ or greater) and confirmed by a 24 hour urine collection (> 1 g/24 hrs). Subjects may be re-screened if proteinuria is shown to be controlled with or without intervention. Subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure > 90 mmHg or systolic blood pressure > 140 mmHg. Subjects may be re-screened if blood pressure is shown to be controlled with or without intervention. The subject has a documented Left Ventricular Ejection Fraction < 50%. Subject is receiving therapeutic anticoagulation therapy. Low dose anti coagulation (e.g., low dose warfarin) for catheter prophylaxis only will be permitted. No low molecular weight heparin (LMW) is allowed. Subject is receiving anti-retroviral therapy for Human Immunodeficiency Virus (HIV). Prophylactic antiviral therapy to prevent Hepatitis B virus (HBV) reactivation is allowed. Female subjects who are pregnant or breast feeding. Presence of  grade 2 encephalopathy by NCI CTCAE criteria. Presence of  grade 2 ascites by NCI CTCAE criteria. Clinically significant uncontrolled condition(s).

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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