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A Phase II Feasibility Study of Sorafenib and Gemcitabine Combination Treatment in Patients With Advanced Hepatocellular Carcinoma

Phase 2
Open (Enrolling)
Hepatocellular Carcinoma

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Trial Information

A Phase II Feasibility Study of Sorafenib and Gemcitabine Combination Treatment in Patients With Advanced Hepatocellular Carcinoma

Over-all Study Design

This is a non-randomized, open-label treatment protocol for patients with advanced HCC.

30 Patients will be treated with 400 mg oral sorafenib twice a day on a continuous basis
with Gemcitabine 1000mg/m2 administered on day 1 & 8 of a 4 week cycle. Patients in this
protocol may continue to be treated with this combination for a minimum of 4 cycles until
any of the following criteria for protocol discontinuation is reached:

1. Progression of disease.

2. The patient is unlikely to benefit from further treatment as

Judged by the Investigator.

3. Intolerable toxicity of the drugs.

4. Withdrawal of consent for any reason.

Dosage, administration and duration

Doses of study drugs may be delayed or reduced in case of clinically significant toxicities
that are possibly, probably or definitely related to protocol therapy. Toxicities will be
graded using the NCI Common Terminology Criteria Version 3.0 (see Appendix 10.6). If a
patient experiences several toxicities and there are conflicting recommendations, the
recommended dose adjustment that reduces the dose to the lowest level should be used. All
dose modifications will follow pre-defined dose levels as indicated below for study drugs,
respectively. The dose modifications of sorafenib will follow the following dose levels:

Dose level 1 (starting dose): 400 mg (2 x 200 mg) p. o. twice daily Dose level 2: 400 mg (2
x 200 mg) p. o. once daily Dose level 3: 400 mg (2 x 200 mg) p. o. once every other day If a
dose reduction by more than two dose levels from the 400 mg twice daily schedule is
required, the patient should be discontinued from the study treatment. Also, at the
discretion of the Investigator, the dose may be re escalated to a higher dose level up to up
to a maximum of 400 mg twice daily following the resolution of the Adverse Event or an
improvement in the Adverse Event to a level which permits the re-escalation of the study

For Gemcitabine the potentially dose limiting toxicity is myelosuppression, dose delays are
allowed for Grade 3 and 4 toxicities. Growth factors will not be administered unless delay
is more than 2 weeks in recovery of hematological toxicity.

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

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

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

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

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

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

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

RECIST criteria for response evaluation by CT sacan abdomen in Target lesion of HCC

Outcome Time Frame:

4 months

Safety Issue:


Principal Investigator

Naeem Naqi, MBBS,FCPS

Investigator Role:

Principal Investigator

Investigator Affiliation:

Consultant Oncologist


Pakistan: Research Ethics Committee

Study ID:




Start Date:

September 2008

Completion Date:

December 2009

Related Keywords:

  • Hepatocellular Carcinoma
  • Hepatocellular Carcinoma
  • Sorafenib
  • Gemcitabine
  • Carcinoma
  • Carcinoma, Hepatocellular