Dose Escalation of Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)

Istituto Clinico Humanitas

Status and phase

Completed

Phase 2

Conditions

Carcinoma, Hepatocellular

Treatments

Drug: Sorafenib (BAY-43-9006)

Study type

Interventional

Funder types

Other

Identifiers

NCT00490685

ONC-2006-004

EUDRACT 2007-000758-30

Details and patient eligibility

About

The aim of the study is to evaluate, after radiological progression, efficacy in patients treated with Sorafenib at a dose of 600 mg bid compared to that in patients treated with best supportive care.

Primary efficacy objective is progression free survival from randomization.

Enrollment

142 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with advanced/inoperable HCC not eligible for radical or loco-regional therapies Male or female patients ≥ 18 years of age Life expectancy of at least 12 weeks at screening Histologically or cytologically documented HCC

At least one tumor lesion that meets both of the following criteria:

The lesion is measurable as per RECIST criteria, and
The lesion has not been subject to previous loco-regional therapy (such as radiation therapy, TACE, TAE, PEI, RFA, or cryoablation) Patients previously treated with loco-regional treatments are eligible provided that previously treated lesions are not selected as target lesions. Local therapy must be completed at least 4 weeks prior to the baseline scan ECOG PS of 0, 1, or 2 Cirrhotic status of Child-Pugh class A or B Barcelona-Clinic Liver Cancer (BCLC) stage B or C

The following laboratory parameters:

Platelet count ≥ 60 x 109 /L
Haemoglobin ≥ 8,5 g/dL
Total bilirubin ≤ 3 mg/dL
Alanine transaminase (ALT) and Aspartato transaminase (AST) ≤ 5 x upper limit of normal
Amylase and lipase < 1,5 x the upper limit of normal
Serum creatinine ≤ 1,5 x the upper limit of normal
Prothrombin time (PT)-international normalized ratio (INR) < 2,3 or PT < 0,6 seconds above control. Patients who are being therapeutically anticoagulated with an agent such as Coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.

Written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.

Exclusion criteria

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 & T1).
Any cancer curatively treated > 3 years prior to entry is permitted Renal failure requiring hemo- or peritoneal dialysis
History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) class 2;
active coronary artery disease (CAD);
cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers ordigoxin), or uncontrolled hypertension.
Myocardial infarction more than 6 months prior to study entry is permitted if there is no evidence of active CAD
Active clinically serious infections (> Grade 2 [NCI CTCAE] )
Known history of human immunodeficiency virus (HIV) infection
Known Central Nervous System tumors including metastatic brain disease
Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
History of organ allograft
Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
Patients unable to swallow oral medications
Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study
Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug.
Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial