Study of Sorafenib and Gemcitabine in Advanced Hepatocellular Carcinoma (HCC)

• Status: Unknown status
• Trial end date: 2009-12-01
• Target enrollment: 0
• Participant gender: All

Summary

For the majority of patients, metastatic HCC is incurable and patients should be considered candidates for clinical trials when appropriate. Till recently there was no worldwide, approved local or systemic therapy for advanced HCC and the available therapies for advanced unresectable and/or metastatic HCC have limited clinical values, with low response rates and little impact on the natural history of the disease. Furthermore, the toxicities associated with these agents can be severe, requiring careful patient selection, and this dramatically decreases the number of patients who may benefit from therapy. The SHARP trial established the survival benefit of Sorafenib in Advanced HCC but the results yet remain humble. The need for more effective therapies is still there.

Study Objectives

The primary objective of this phase II study is to evaluate the efficacy and safety of Sorafenib and Gemcitabine combination in patients with advanced HCC.

Safety data and limited efficacy data will be collected for this combination in the study. All Drug-Related Adverse Events, all Adverse Events NCI CTCAE Version 3.0 Grade 3 or higher, and all Serious Adverse Events regardless of causal relationship to study drugs will be recorded in this study.

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

Details

• Lead Sponsor: Combined Military Hospital, Pakistan
• Collaborator: Bayer
• Treatments: Gemcitabine; Niacinamide; Sorafenib

Criteria

Inclusion Criteria:

1. Advanced Hepatocellular carcinoma

2. Histologically proven

3. Child-Pugh A and B

4. Age > 18 years.

5. ECOG Performance Status of 0 or1

6. Life expectancy of at least 12 weeks.

7. Subjects with at least one uni-dimensional (for RECIST) or bi-dimensional (for WHO) measurable lesion. Lesions must be measured by CT-scan or MRI

8. Adequate bone marrow, liver and renal function as assessed by the following

• Hemoglobin > 9.0 g/dl

• Absolute neutrophil count (ANC) >1,500/mm3

• Platelet count ³ 100,000/μl

• Total bilirubin < 1.5 times the upper limit of normal

• ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)

• Alkaline phosphatase < 4 x ULN

• PT-INR/PTT < 1.5 x upper limit of normal [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.]

• Serum creatinine < 1.5 x upper limit of normal. (normal creatinine value: 0.8-1.2 mg/dl)

• Signed and dated informed consent before the start of specific protocol procedures.

Exclusion Criteria:

1. History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or Digoxin are permitted) or uncontrolled hypertension.

2. History of HIV infection

3. Active clinically serious infections (> grade 2 NCI-CTC version 3.0)

4. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)

5. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)

6. History of organ allograft however, the organ allograft may be allowed as protocol specific.

7. Patients with evidence or history of bleeding diasthesis

8. Patients undergoing renal dialysis

9. 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 bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.

Excluded therapies and medications, previous and concomitant:

1. Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry.

2. Major surgery within 4 weeks of start of study

3. Use of biologic response modifiers, such as G-CSF, within 3 week of 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 2 months prior to the study or during the study]

4. Investigational drug therapy outside of this trial during or within 4 weeks of study entry

5. Prior exposure to the study drug.

6. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial (and men for at least 3 months after last administration of study medication). Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results

7. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study