A Phase III randomized, placebo-controlled study of sorafenib in patients with advanced hepatocellular carcinoma

• Conditions: Advanced hepatocellular carcinoma; MedDRA version: 7.1Level: LLTClassification code 10049010

• Registration Number: EUCTR2004-001773-26-DE
• Lead Sponsor: Bayer HealthCare AG, D-51368 Leverkusen Germany

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-02-16
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 560

Inclusion Criteria

Primary diagnosis
Patients with advanced HCC, ECOG PS 0, 1, or 2, Child-Pugh status A, who have not received prior systemic anti-cancer treatment for HCC.

Inclusion Criteria:
•Male or female patients > 18 years of age
•Patients who have a life expectancy of at least 12 weeks
•Patients with advanced HCC
•Patients with histologically or cytologically documented HCC (original biopsy at first diagnosis is acceptable)
•Patients must have at least one tumor lesion that meets both of the following criteria:
? The lesion can be accurately measured in at least one dimension according to RECIST
? The lesion has not been previously treated with local therapy (such as surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation)
•Patients who have received local therapy, such as surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible. Previously treated lesions will not be selected as target lesions. Local therapy must be completed at least 4 weeks prior to the baseline scan.
•Patients who have an ECOG PS of 0, 1, or 2
•Cirrhotic status of Child-Pugh class A only. Child-Pugh assessment is to be carried out during the screening period.
The following laboratory parameters:
?Platelet count >= 60 x 109/L
?Hemoglobin >= 8.5 g/dL
?Total bilirubin <= 3 mg/dL
?Albumin >= 2.8 g/dL
?Alanine transaminase (ALT) and 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 <= 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.
• Patients who give 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.

Extension with Crossover Phase
The inclusion criteria required for this segment of the study are the following:
•Patients must provide 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.
•Patients must either be currently participating in the double-blind portion of the study, or are currently in follow-up.
•A patient who had previously discontinued double-blind therapy due to a drug related toxicity and after unblinding was determined to have been on sorafenib, must be re-assessed by the investigator who must judge whether the patient may derive benefit from re-starting sorafenib treatment. The toxicity responsible for treatment discontinuation must resolve or improve to a level that allows re-initiation of sorafenib therapy.
•Prior use of systemic anti-cancer therapy is allowed but concomitant systemic anti-cancer therapy is not allowed.
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

• 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 or digoxin), or uncontrolled hypertension. Myocardial infarction more than 6 months prior to study entry is permitted.
• Active clinically serious infections (> grade 2 National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [CTCAE] version 3.0)
• 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
• Known or suspected allergy to the investigational agent or any agent given in association with this trial
• 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.

Excluded therapies and medications, previous and concomitant
• Prior use of any systemic anti-cancer chemotherapy for HCC
• Prior use of systemic investigational agents for HCC
• Prior use of Raf-kinase inhibitors (RKI), VEGF inhibitors, MEK inhibitors or Farnesyl transferase inhibitors
• Major surgery within 4 weeks of start of study drug
• Radiotherapy during study or within 3 weeks prior to start of study drug. (Palliative radiotherapy will be allowed as described in Prior and Concomitant Therapy)
• Use of biologic response modifiers, such as granulocyte colony-stimulating factor (G-CSF), within 3 weeks prior to study entry. (G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction). Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 1 month prior to the study or during the study.
• Autologous bone marrow transplant or stem cell rescue within four months of start of study drug
• Concomitant treatment with rifampin and St John’s wort

Extension with Crossover Phase
The exclusion criterion required for this segment of the study is the following:
•Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to enrolling in this portion of the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified