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)

Phase 3

Completed

• Conditions: hepatoma; Liver cell cancer; 10019815

• Registration Number: NL-OMON34685
• Lead Sponsor: Abbott

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 30

Inclusion Criteria

Each subject must fulfill all of the following criteria within 21 days prior to the first day of therapy.
1) Subject must be >= 18 years of age.
2) Subject must be diagnosed with unresectable or metastatic HCC defined by:
* Histologic or cytologic diagnosis OR
* European Association for the Study of Liver Criteria
3) Radiological criteria: two coincident imaging techniques (Four techniques considered: ultrasound, spiral computed tomography (CT), magnetic resonance imaging (MRI) and angiography)
4) Focal lesion > 2 cm with arterial hypervascularization
5) Combined criteria: one imaging technique associated with AFP (alpha fetoprotein) > 400 ng/mL
6) 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.
7) Subjects must show signs of progression (i.e., new lesion per RECIST version 1.1) if prior
liver-directed therapy was received.
8) Subject has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 1.
9) Subject must have the following laboratory values:
* Total Bilirubin <= 3.0 mg/dL or equivalent
* AST/ALT <= 5 × ULN
* PTT <= 1.5 × ULN and INR < 1.5
* ANC >= 1.0 × 109/L
* Platelet count >= 50 × 109/L if splenomegaly; if splenomegaly is not present, platelet count >= 75 × 109/L
* Creatinine <= 1.5 × ULN
* Serum albumin >= 2.8 g/dL
* PT <= 6 seconds prolonged
10) 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.
11) 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).

Exclusion Criteria

1) Subject has received prior systemic (administered intravenously or orally rather than
locoregionally) treatment for HCC.
2) Subject has Child-Pugh grade Class B or C hepatic impairment.
3) 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.
4) 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).
5) 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.
6) 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.
7) 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.
8) The subject has a documented Left Ventricular Ejection Fraction < 50%.
9) 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.
10) Subject is receiving anti-retroviral therapy for Human Immunodeficiency Virus (HIV).
Prophylactic antiviral therapy to prevent Hepatitis B virus (HBV) reactivation is allowed.
11) Female subjects who are pregnant or breast feeding.
12) Presence of > grade 2 encephalopathy by NCI CTCAE criteria.
13) Presence of >= grade 2 ascites by NCI CTCAE criteria.
14) Clinically significant uncontrolled condition(s).

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary efficacy analysis will be a comparison of overall survival (OS)<br /><br>distributions between the linifanib and sorafenib treatment groups.<br /><br>Time to death for a given subject will be defined as the number of days from<br /><br>the date that the subject was randomized to the date of the subject's death.<br /><br>All events of death (up to the 667th death for final analysis) will be<br /><br>included, regardless of whether the event occurred while the subject was still<br /><br>taking study drug, or after the subject discontinued study drug. If a subject<br /><br>has not died, then the data will be censored at the date when the subject was<br /><br>last known to be alive.</p><br>