Hepatocarcinoma assessment randomized protocol sharp. Study to compare selective internal radiation therapy. A randomized, doubleblind, placebocontrolled, international, multicenter, phase 3. Mean relative bioavailability is 3849% when compared with oral solution. Sorafenib in advanced hepatocellular carcinoma journal of.
Sorafenib tosylate pharmacokinetics absorption bioavailability. Impact of viral status on survival in patients receiving. Randomized protocol sharp, nct00105443 trial demonstrated an increase in median overall survival time and. Efficacy and safety of sorafenib in patients in the asia. Sorafenib hcc assessment randomized protocol sharp is a phase iii, multicenter, randomized, placebocontrolled trial.
Sorafenib in patients with hepatocellular carcinomaresults of the. Tablets containing sorafenib tosylate 274 mg equivalent to 200 mg of sorafenib. This large, multicenter, randomized, placebocontrolled phase iii trial evaluated the efficacy and safety of sor vs placebo p in pts. In this randomized trial involving 602 patients with advanced hepatocellular carcinoma, sorafenib, a multikinase inhibitor o. Phase ii study of sorafenib in patients with advanced hepatocellular carcinoma. Sharp sorafenib hcc assessment randomized protocol. Methods in this multicentre, randomised, doubleblind, placebocontrolled, phase 3 trial decision, we investigated sorafenib 400 mg orally twice daily in patients with radioactive iodinerefractory locally advanced or metastatic. Nexavar sorafenib dose, indications, adverse effects. The sharp trial evaluated patients with nonsurgical hepatocellular carcinoma with child pugh liver function class a cirrhosis and randomized them to sorafenib versus placebo. However, because these trials did not include any japanese patients, the ef. Request pdf sorafenib therapy in advanced hepatocellular carcinoma. No effective therapy is available for advanced hepatocellular carcinoma.
The sharp trial has demonstrated that sorafenib is effective in prolonging median survival and timetoprogression in patients with advanced hcc and that it is generally well tolerated with a manageable adverse events profile. In the sharp trial, sorafenib 400 mg twice daily significantly prolonged overall survival os from 7. Randomized phase iii trial of sorafenib versus placebo in. Trial of sorafenib in hepatocellular cancer hcc transplant patients. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation. In this randomized trial involving 602 patients with advanced hepatocellular carcinoma, sorafenib, a.
Sorafenib codeveloped and comarketed by bayer and onyx pharmaceuticals as nexavar, is a kinase inhibitor drug approved for the treatment of primary kidney cancer advanced renal cell carcinoma, advanced primary liver cancer hepatocellular carcinoma, flt3itd positive aml and radioactive iodine resistant advanced thyroid carcinoma. Sorafenib is first systemic therapy to prolong survival in hcc patients. Nexavar tablets are round, biconvex, red filmcoated tablets, debossed with the bayer cross on one side and 200 on the other side. In this investigatorinitiated, multicenter, phase iii trial, patients were randomized to receive sorafenib alone arm s, n 169 or in combination with. Purpose openlabel, phase iii trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endo. The strong evidence of sorafenib offering significant survival benefit in advanced hcc was derived from the sharp sorafenib hcc assessment randomized protocol trial 12. The sharp trial until now, no effective systemic treatment options have been. A phase ii and biomarker study of sorafenib combined with. However, those trials conducted a rigorous patient selection. Efficacy and safety of selective internal radiotherapy.
The results of our sharp trial subgroup analyses suggest that the efficacy and safety of sorafenib, relative to placebo, in patients with advanced hcc and wellpreserved liver function do not appear to be affected by baseline health status, disease etiology, tumor burden, tumor stage, or prior therapy. Sorafenib in advanced hepatocellular carcinoma n engl j med 359. In 2008, the sharp trial a phase 3 study of sorafenib in patients with advanced hcc, clinicaltrials. Sorafenib has been studied in multiple different tumor types with notable advances in advanced hepatocellular carcinoma and renal cell carcinoma. Combined sorafenib and yttrium90 radioembolization for. A similar tolerability profile was seen in the asiapacific trial. Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the asiapacific region, and is well tolerated. Iii, randomized, doubleblind, placebocontrolled trial. Another interesting endpoint was the almost doubling of the time to radiologic progression in the sharp trial. Another phase iii clinical trial enrolling patients from the asia. In this multicenter, phase 3, doubleblind, placebocontrolled trial, we randomly. Find out if sorafenib has any effect on patient reported outcomes.
Sorafenib for the treatment of advanced hepatocellular. In a multicenter, randomized, doubleblind clinical trial, treatment with sorafenib significantly improved progressionfree survival pfs compared with placebo in patients with locally recurrent or metastatic, progressive, differentiated thyroid cancer refractory to radioactive iodine 10. The study null hypothesis is, there is no difference in overall survival between patients receiving sirt and those receiving sorafenib therapy. Sorafenib in the treatment of advanced hepatocellular carcinoma. Taken together with data from the sorafenib hepatocellular carcinoma assessment randomised protocol sharp trial, sorafenib seems to be an appropriate option for the treatment of. The phase iii sharp trial showed a median timetoprogression mttp of 5. Safety and efficacy of sorafenib in patients with child. Aboualfa, lawrence schwartz, sergio ricci, dino amadori, armando santoro, arie figer. Sorafenib nexavar is an orally active multikinase inhibitor that is approved in the eu for the treatment of hepatocellular carcinoma.
To address this, we undertook an individual patient data. Sorafenib in advanced hepatocellular carcinoma request pdf. Taken together with data from the sorafenib hepatocellular carcinoma assessment randomised protocol sharp trial, sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma. Patients consecutively admitted to three referral centers who were receiving best supportive care following permanent discontinuation of sorafenib for any reason were. Find out if patients receiving sorafenib will live longer.
There is no standard of care for adjuvant therapy for patients with hepatocellular carcinoma. Sorafenib is a standard firstline treatment for advanced hepatocellular carcinoma hcc. Sorafenib sor is a multikinase inhibitor with antiangiogenic, proapoptotic and raf kinase inhibitory activity, with clinical activity in a phase ii hcc trial. As expected given the addition of a chemotherapy agent, the adverse event profile in patients with advanced hepatocellular carcinoma who received combination therapy with sorafenib plus doxorubicin differed somewhat to that seen with sorafenib monotherapy in the sharp trial. State of the art jeanluc raoul institut paolicalmettes, marseille france esmo summit africa, cape town, 1012 february 2017. Clinical trials are research studies that involve people. Adjuvant sorafenib for hepatocellular carcinoma after. We undertook this phase 3, doubleblind, placebocontrolled.
Phase ii study of sorafenib in patients with advanced. Pdf sorafenib with transarterial chemoembolization. This is a randomized controlled trial that compared sorafenib nexavar to placebo in patients. Clinical trials using sorafenib tosylate national cancer. Sharp, sorafenib hcc assessment randomized pro tocol in 602 patients with advanced hcc and. The results of the sharp trial led to the approval of sorafenib by the us food and drug administration for the treatment of hcc, and this agent is currently the only systemic therapy approved for this disease. Macroscopic vascular invasion portal vein andor extrahepatic spread. Sorafenib for the treatment of advanced hepatocellular carcinoma.
Sunitinib versus sorafenib in advanced hepatocellular. Patients and methods patients were stratified and randomly assigned to receive sunitinib 37. Reflecta phase 3 trial comparing efficacy and safety of. We conducted a second multinational, randomised controlled, phase iii trial the sorafenib ap trial which evaluated the efficacy and safety of sorafenib in patients with advanced hcc from the ap region. Nct00105443 trial demonstrated an increase in median. It is not known whether a drug which is considered primarily cytostatic will be effective in preventing cancer. Phase ii study of sorafenib in patients with advanced hepatocellular carcinoma ghassan k. All trials on the list are supported by nci ncis basic information about clinical trials explains the types and phases of trials and how they are carried out. Sorafenib in radioactive iodinerefractory, locally. Sorafenib therapy in advanced hepatocellular carcinoma. Determine the pharmacokinetics pk in patients with liver cancer.
The results seen with sorafenib in the phase iii sharp trial suggest that vegf and raf kinase inhibition prolong survival in patients with advanced hcc. Clinical trials look at new ways to prevent, detect, or treat disease. In this multicenter, phase 3, doubleblind, placebocontrolled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib at. Find out if sorafenib prevents the growth of or shrinks liver tumors andor their metastases. Listing a study does not mean it has been evaluated by the u. Sorafenib in patients with hepatocellular carcinoma results of the. Nexavar in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer. The sharp trial has demonstrated that sorafenib is effective in prolonging median survival and timetoprogression in patients with advanced hcc and that it is generally well tolerated with a.
A phase iii study of sorafenib in patients with advanced hepatocellular carcinoma sharp the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Nexavar significantly extended os vs placebo in the sharp clinical trial 1. The sorafenib hepatocellular carcinoma hcc assessment randomized protocol sharp trial demonstrated that sorafenib improves overall survival and is. A phase iii study of sorafenib in patients with advanced. Get emergency help right away if you get symptoms such as chest pain, shortness of breath, racing heartbeat, swelling in lower legs, feet and abdomen, feel lightheaded or faint. Sorafenib in advanced hepatocellular carcinoma nejm. In another phase iii clinical trial with similar design to the sharp study, the efficacy of sorafenib in the asian population was evaluated.
In this multicenter, phase 3, double blind, placebocontrolled trial, we randomly as signed 602. In the sharp hcc study, the incidence of cardiac ischemiainfarction was 2. Monotherapy with sorafenib prolongs overall survival and. Pacific region concluded that sorafenib was a well. Efficacy and safety of selective internal radiotherapy with yttrium90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma sarah. Listing a study does not mean it has been evaluated by.
The clinical trials on this list are studying sorafenib tosylate. Efficacy and safety of sorafenib in patients with advanced. Before starting nexavar, tell your doctor if you have. In this multicenter, phase 3, doubleblind, placebocontrolled trial, we randomly as signed 602. The primary objective of this study is to assess the efficacy of sirt as compared with sorafenib in patients with locally advanced liver cancer in terms of overall survival os. The asiapacific trial, in the eastern population, also demonstrated an improvement in median os in favor of sorafenib 6. In 2008, the multicentre phase iii doubleblind randomized placebocontrolled sharp clinical trial 14, conducted in patients with advanced hcc, demonstrated that, compared with placebo, sorafenib conferred a survival advantage of 3 months hazard ratio.950 744 286 864 8 816 684 1462 435 1312 76 1043 1115 918 1219 818 372 1512 1171 288 713 1479 1338 754 1040 1277 620 155 421