Clinical trial NCT00490685: Dose Escalation of Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)
Official title: Randomized Continuation, Dose Escalation Trial of Sorafenib in Patients With Advanced HCC With Radiological Progression on Prior Sorafenib Treatment (Phase II Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Istituto Clinico Humanitas
Sponsor class: OTHER
First posted: 2007-06-25
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

1. The lesion is measurable as per RECIST criteria, and
2. 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milan
Study officials:
affiliation: Istituto Clinico Humanitas
name: Armando Santoro, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Lathia C, Schwartz B, Taylor I, Moscovici M, Saltz LB. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2006 Sep 10;24(26):4293-300. doi: 10.1200/JCO.2005.01.3441. Epub 2006 Aug 14.
citation: Rimassa L, Pressiani T, Boni C, Carnaghi C, Rota Caremoli E, Fagiuoli S, Foa P, Salvagni S, Cortesi E, Chiara Tronconi M, Personeni N, Bozzarelli S, Chiara Banzi M, Fanello S, Romano Lutman F, Giordano L, Santoro A. A phase II randomized dose escalation trial of sorafenib in patients with advanced hepatocellular carcinoma. Oncologist. 2013;18(4):379-80. doi: 10.1634/theoncologist.2012-0221. Epub 2013 Apr 11.