Study of Sorafenib With Combination of Thalidomide in Hepatocellular Carcinoma (HCC)

• Status: Terminated
• Trial end date: 2010-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this phase I study is to determine the maximal tolerable dose (MTD) of thalidomide (THADO®) in combination with fixed dose of sorafenib (NEXAVAR®) for the treatment of advanced or metastatic HCC.

The Phase II purpose of this study is to determine the disease control rate (complete response + partial response + stable disease) for at least 4 months of sorafenib (NEXAVAR®) plus phase I determined MTD of thalidomide (THADO®) in patients with advanced or metastatic HCC.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Health Research Institutes, Taiwan
• Collaborators: Chang Gung Memorial Hospital; National Cheng-Kung University Hospital
• Treatments: Niacinamide; Sorafenib; Thalidomide

Criteria

Inclusion Criteria:

• Patients must be at least 18 years of age.

• With histologically or cytologically documented HCC or clinically diagnosed HCC.

• Advanced (surgically unresectable and unsuitable for local therapy), and/or metastatic HCC, and/or patient refused local therapy.

• Performance status of ECOG score 0-2.

• Life expectancy of at least 12 weeks.

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

• measurable (must be by CT-scan or MRI) in at least one dimension according to RECIST;

• the lesion has not been previously treated with local therapy, such as radiation therapy, hepatic arterial (chemo) embolization, radiofrequency ablation, and percutaneous interventional therapy.

• Previous local therapy, such as radiotherapy, hepatic arterial (chemo)embolization, radiofrequency ablation, percutaneous interventional therapy, is allowed but the treatment must be completed at least 4 weeks prior to the baseline scan.

• Patients have adequate bone marrow reserves defined as:

• ANC ≧ 1,500/μl;

• Platelets count ≧ 75,000/μl;

• Hemoglobin ≧ 8.5 g/dl.

• Adequate liver and renal functions defined as:

• Child-Turcotte-Pugh score of 7 or lower (class A and well-compensated class B);

• Liver transaminase (ALT) ≦ 5 x upper limit of normal (ULN);

• Serum total bilirubin ≦ 3mg/dl;

• Serum albumin ≧ 2.8 g/dl;

• Prothrombin time (PT)-internal normalized ration (INR) ≦ 2.3 or partial thrombin time (PTT) ≦ 6 seconds above control;

• Serum creatinine ≦ 1.5 x ULN.

• Women of childbearing potential and men must agree to use adequate contraception, prior to study entry, during treatment, and at least 3 months after last dose of treatment.

• Patients must understand the protocol and sign a written informed consent.

Exclusion Criteria:

• Previous use of systemic anti-cancer therapy for HCC such as chemotherapy, immunotherapy, and targeting therapy within 4 weeks to study entry.

• Patients with prior use of investigational drugs including sorafenib and thalidomide.

• Active cardiac disease, including CHF NYHA class > 2, active CAD, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta-blockers or digoxin, and uncontrolled hypertension.

• Patients with hemorrhagic diathesis or have history of active bleeding with 30 days prior to study entry.

• History of HIV infection.

• Active or uncontrolled infections requiring antibiotics treatment.

• Metastatic brain or leptomeningeal tumours unless the patients is > 6 months from definitive therapy, has negative imaging study within 4 weeks of study entry, and is clinically stable with respect to the tumour at the time of study entry.

• With seizure disorder requiring medication (such as steroids or anti-epileptics).

• History of organ allograft.

• Undergoing renal dialysis.

• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bluffer tumours [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.

• Pregnant or breast-feeding patients.