Study of Sorafenib and Gemcitabine in Advanced Hepatocellular Carcinoma (HCC) (HCC)
Recruitment status was: Recruiting
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.
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Feasibility Study of Sorafenib and Gemcitabine Combination Treatment in Patients With Advanced Hepatocellular Carcinoma|
- RECIST criteria for response evaluation by CT sacan abdomen in Target lesion of HCC [ Time Frame: 4 months ] [ Designated as safety issue: No ]
- Toxicity evaluation in accordance with CTCAE v3.0 [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2008|
|Estimated Study Completion Date:||December 2009|
|Estimated Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
Patients will be treated with 400 mg oral sorafenib twice a day on a continuous basis. 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:
Other Name: NexavarDrug: Gemcitabine
Patients will be treated 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:
Progression of disease. The patient is unlikely to benefit from further treatment as
Judged by the Investigator.
Intolerable toxicity of the drugs. Withdrawal of consent for any reason.
Other Name: Gemzar
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:
- Progression of disease.
The patient is unlikely to benefit from further treatment as
Judged by the Investigator.
- Intolerable toxicity of the drugs.
- 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 drug.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00844688
|Combined Military Hospital|
|Rawalpindi, Punjab, Pakistan, 46000|
|Principal Investigator:||Naeem Naqi, MBBS,FCPS||Consultant Oncologist|