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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
RECIST criteria for response evaluation by CT sacan abdomen in Target lesion of HCC
Naeem Naqi, MBBS,FCPS
Pakistan: Research Ethics Committee