Sorafenib-RT in Treating Hepatocellular Carcinoma (SHEP)
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The incidence is highest in Asia and it is increasing in North America, with a two to three fold increase in mortality in North America expected over the next two decades. Previous research has shown that tumours often have abnormal blood vessels that may reduce the effect of radiation therapy. New drugs, known as "anti-angiogenic" drugs have been shown in animal and human studies to damage or change tumour blood vessels in ways that may make tumors more sensitive to radiation treatment. 38-44 patients diagnosed with HCC will be invited to take part in this study. Upon completion, this study will establish the safety of the combination of radiation and sorafenib in patients with HCC. This will also establish preliminary data regarding efficacy of the combination and investigate potential imaging and serum/tissue markers surrogates for tumor response and/or drug activity.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Sorafenib and Radiation Therapy in Patients With Hepatocellular Carcinoma|
- Determine the MTD of sorafenib and RT in patients with hepatocellular carcinoma using an iso-toxicity radiation dose allocation scheme. Determine the acute toxicity (< 3 months) of sorafenib when combined with RT. [ Time Frame: 1 year enrollment; 5 years follow-up ] [ Designated as safety issue: Yes ]
- Determine late toxicities, in-field local control at 3 months, overall survival, progression time, and progression free survival. Quantify alteration in perfusion parameters.Assess serum and tissue biomarkers. Assess quality of life in these patients. [ Time Frame: 1 year enrollment; 5 years follow-up ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2009|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
|Experimental: Sorafenib + RT||
Patients will receive sorafenib alone (following the dose escalation scheme) for one week, followed by 2 weeks of concurrent administration of sorafenib with conformal radiation therapy (6 fractions over two weeks). Sorafenib administration will continue for four weeks following completion of radiation. At three months following radiation, when liver toxicity is assessed, full dose sorafenib (400mg PO BID) will then be initiated and continued until disease progression or serious toxicity occurs, to a maximum time of 12 months.
The study design will include 2 radiation strata of patients, with a constant radiation dose for strata 1 requiring a low volume of liver to be irradiated, and a variable dose defined based on the effective liver volume irradiated in the second strata, which will require more liver volume to be irradiated, based on our prior experience. Both stratas one and two will be accrued concurrently. Biologic response will be assessed using standard contrast CT scans. Correlative studies of biological markers, perfusion CT, and microbubble contrast enhanced ultrasound will also be performed.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00892658
|University Health Network|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Laura Dawson, MD||University Health Network, Princess Margaret Hospital|
|Principal Investigator:||Anthony Brade, MD||University Health Network, Toronto|