Another phase iii clinical trial enrolling patients from the asia. Clinical trials are research studies that involve people. Patients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as tace and ablation, to prevent tumor progression and dropout and to improve longterm outcome after transplantation. Reflecta phase 3 trial comparing efficacy and safety of. Sorafenib has been studied in multiple different tumor types with notable advances in advanced hepatocellular carcinoma and renal cell carcinoma. Efficacy and safety of transarterial chemoembolization. Evidence for the clinical benefit of sorafenib comes from the sharp trial. We conducted a phase ii trial of singleagent sorafenib in patients with advanced biliary tract carcinoma. However, the efficacy of sorafenib is only moderate with a median survival of 10. Based on an interim analysis of the first 75 patients enrolled, the observed improvement in progression free survival exceeded the trialdesign target. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma and vascular invasion or extrahepatic spread. Hepatocarcinoma assessment randomized protocol sharp. In this trial, about quarter of patients discontinue sorafenib due to drugrelated side effects.
Sorafenib treatment resulted in a median overall survival of 9. Ten years of sorafenib in hepatocellular carcinoma. In this multicenter, phase 3, doubleblind, placebocontrolled trial, we randomly as signed 602. Find out if sorafenib has any effect on patient reported outcomes. Results early trial termination occurred for futility and safety reasons. Sorafenib in advanced hepatocellular carcinoma new england. The hypothesis of the study was that sorafenib could reduce tumor recurrence and therefore improve the overall survival. This was a multicenter retrospective study including hcc patients treated with sorafenib between october 2007 and march 2014, with the aim of evaluating patients who achieved cr according to recist 1. Cancers free fulltext sorafenib with transarterial. Highlights of prescribing information these highlights. The strong evidence of sorafenib offering significant survival benefit in advanced hcc was derived from the sharp sorafenib hcc assessment randomized protocol trial 12. Request pdf sorafenib therapy in advanced hepatocellular carcinoma. Haddad, md, summarizes the decision trial and the approval of sorafenib. Sorafenib in advanced hepatocellular carcinoma nejm.
The sharp trial until now, no effective systemic treatment options have been available for patients with unresectable. What it is used for for treating certain types of leukemia and cancers which start in the liver, kidney or thyroid. Nexavar sorafenib dose, indications, adverse effects. Phase ii trial of sorafenib in combination with capecitabine. Sorafenib in advanced hepatocellular carcinoma n engl j med 359. A prospective clinical trial on sorafenib treatment of. In this multicenter, phase 3, doubleblind, placebocontrolled trial, we randomly. This rate was lower than observed in the sharp trial which. Sunitinib versus sorafenib in advanced hepatocellular cancer.
No effective therapy is available for advanced hepatocellular carcinoma. Background no effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A phase iii study of sorafenib in patients with advanced. Sorafenib in radioactive iodinerefractory, locally. Sorafenib, a multikinase inhibitor of vegfr23, pdgfr. The largest biomarker study conducted to date is the sharp trial4. The clinical trials on this list are studying sorafenib tosylate. Tell your healthcare provider about all the medicines you take, including prescription and overthecounter medicines, vitamins, and herbal supplements.
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. We evaluated the combination of sorafenib and modified m. Trc105 and sorafenib demonstrated encouraging evidence of activity, including a 33% partial response rate 515 pts by recist, at rp2d doses of trc105 duffy 2017. Adverse events were consistent with the known safety profile of sorafenib. An improved overall survival was demonstrated in the sorafenib arm versus placebo arm 10. This was a groundbreaking advancement in the field of hcc. The effects of lowering ldl cholesterol with a statin in populations without chronic kidney disease have been described by the cholesterol treatment trialists ctt collaboration, and show that statin therapy reduces the risk of myocardial infarction or coronary death, stroke, or coronary revascularisation by about a fifth per 1 mmoll ldl. It showed a 44% improvement in overall survival, with a median overall survival of 10. The sorafenib hepatocellular carcinoma hcc assessment randomized protocol sharp trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced hcc. Highlights of prescribing information these highlights do not include all the information needed to use nexavar safely and effectively. Nov 24, 2009 advanced biliary tract carcinoma has a very poor prognosis, with chemotherapy being the mainstay of treatment. An open label phase 1b2 trial of trc105 and sorafenib in. Pacific region concluded that sorafenib was a well. Ncis basic information about clinical trials explains the types and phases of trials and how they are carried out.
Sorafenib was approved for the treatment of patients with advanced hcc on the basis of the efficacy and the safety results reported by two international randomized, controlled trials rcts, the sharp sorafenib hcc assessment randomized protocol and the asiapacific trials 4,5. The sorafenib hepatocellular carcinoma assessment randomized protocol sharp trial and the asiapacific parallel study have demonstrated that the antiproliferative and antiangiogenic molecularlytargeted agent, sorafenib, which is an oral multikinase inhibitor, improves the overall survival os in patients with ahcc when it was administered at a dose of 400 mg twice a day, when. Oct 22, 2016 sorafenib, a multikinase inhibitor, is the only approved systemic therapy for patients with unresectable or metastatic disease. Sorafenib in patients with hepatocellular carcinomaresults of the. Nevertheless, the median overall patient survival in the sorafenib group in our study 43 weeks was similar to that in the sharp trial 10. Pugh class a patients with an eastern cooperative oncology group ecog status of 0. Findings this phase 3 clinical trial randomized 356 eligible patients to treatment with doxorubicin plus sorafenib vs sorafenib alone. Sorafenib in patients with advanced biliary tract carcinoma. Objective sorafenib is the standard systemic therapy for advanced hepatocellular carcinoma hcc. These results suggest that sorafenib is a new treatment option for patients with progressive radioactive iodinerefractory differentiated thyroid cancer. A phase ii and biomarker study of sorafenib combined with. Consider permanent discontinuation of sorafenib if bleeding necessitates medical intervention. The poor tolerability of sorafenib may be a barrier for treatment maintaining and exposure. We wanted to prospectively assess feasibility of systemic antitumor treatment with sorafenib as neoadjuvant.
A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endo. Results of the sharp trial suggest that patients with hepatitis c may have an added survival advantage associated with sorafenib therapy. Sorafenib in radioactive iodinerefractory, locally advanced. The primary endpoint was median overall survival, which showed a 44% improvement in patients who received sorafenib compared to placebo hazard ratio 0. Sunitinib versus sorafenib in advanced hepatocellular. Survival benefits of resectionlocal ablation for early hcc are compromised by 70% 5year recurrence rates. Tablets containing sorafenib tosylate 274 mg equivalent to 200 mg of sorafenib. The sharp trial evaluated patients with nonsurgical hepatocellular carcinoma with child pugh liver function class a cirrhosis and randomized them to sorafenib versus placebo. Find out if sorafenib prevents the growth of or shrinks liver tumors andor their metastases.
The primary and secondary endpoints of the trial were the recurrence free survival and overall survival and safety. Highlights of prescribing information these highlights do. Sharp trial sorafenib hepatocellular carcinoma assessment. Sep 30, 20 purpose openlabel, phase iii trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer. If you are unable to swallow sorafenib, talk to your care provider or pharmacist for possible options. Vol 384 july 26, 2014 319 sorafenib in radioactive iodinerefractory, locally advanced or metastatic di. Sorafenib significantly improved progression free survival compared with placebo in patients with progressive radioactive iodinerefractory differentiated thyroid cancer. The phase 3 storm trial comparing sorafenib with placebo as adjuvant treatment did not achieve its primary endpoint of improving recurrence free survival rfs. Sorafenib 400 mg was administered orally at a dose of 400 mg 2 x 200 mg tablets twice daily bid. Purpose openlabel, phase iii trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer. Randomized trials and endpoints in advanced hcc journal of.
The search sorafenib and erlotinib, a randomized trial protocol for the treatment of patients with hepatocellular carcinoma study was a randomized, doubleblind, placebocontrolled, phase iii trial conducted at 128 centers in 26 countries in europe, north and south america, and the asiapacific region, enrolling patients age. Systemic treatment for advanced hepatocellular carcinoma. Molecular predictors of prevention of recurrence in hcc. The phase iii sharp trial showed a median timetoprogression mttp of 5. In the dtc trial, the incidence of bleeding was 17.
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. Sorafenib hcc assessment randomized protocol sharp is a phase iii. 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. Monotherapy with sorafenib prolongs overall survival and delays the time to progression in patients with advanced hepatocellular carcinoma who are not candidates for potentially curative treatment or transarterial chemoembolization. Mean relative bioavailability is 3849% when compared with oral solution. The sharp trial investigated the efficacy usefulness of the oral multikinase inhibitor sorafenib nexavar in the treatment of hepatocellular carcinoma. This study showed that the combination of sorafenib and capecitabine in patients with advanced hcc is an active and safe palliative regimen. The phase 3 storm trial comparing sorafenib with placebo as adjuvant treatment did not achieve its primary endpoint of improving recurrence free survival. The sharp trial 2 and asiapacific trials 3 confirmed the efficacy of sorafenib in advanced hcc. The estimated rate of progressionfree survival at 4 months was 62% in the. The trial was designed to target an improvement in median progression free survival from six months for placebo to 15 months for sorafenib. Sorafenib in the treatment of 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. Selection of patients with hepatocellular carcinoma for. All participants in doubleblind phase randomized to sorafenib treatment data before oct 17, 2006. Results demonstrated no difference in median overall survival 9. Efficacy and safety of sorafenib in patients with advanced. Rcc after demonstrating a twofolds increase in progressionfree survival in treated patients. In a multicenter, randomized, doubleblind, phase 3 clinical trial, treatment with sorafenib significantly improved median progression free survival pfs compared with placebo in patients with advanced renal cell carcinoma rcc who had received one prior systemic therapy 5. Sorafenib in advanced hepatocellular carcinoma request pdf.
However, because these trials did not include any japanese patients, the ef. Sorafenib improved progressionfree survival in desmoid. In this trial, 602 patients with wellpreserved liver function 95% childpugh a were randomized to receive either sorafenib 400 mg or matching placebo. Listing a study does not mean it has been evaluated by. Because of this trial sorafenib obtained fda approval for the treatment of advanced hepatocellular carcinoma in november 2007. A similar tolerability profile was seen in the asiapacific trial. Oct 15, 2012 sorafenib nexavar is an orally active multikinase inhibitor that is approved in the eu for the treatment of hepatocellular carcinoma. A recent phase iii trial has shown that sorafenib significantly extends survival.
The sorafenib for hepatocellular carcinoma hcc in adjuvant. 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 a standard firstline treatment for advanced hepatocellular carcinoma hcc. Selection of patients with hepatocellular carcinoma for sorafenib. Nexavar tablets are round, biconvex, red filmcoated tablets, debossed with the bayer cross on one side and 200 on the other side. Do not breastfeed during treatment with nexavar and for 2 weeks after receiving the last dose of nexavar. Sorafenib was administered at a dose of 400 mg twice a day.
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. Clinical trials look at new ways to prevent, detect, or treat disease. Efficacy and safety of transarterial chemoembolization plus. 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 advanced or metastatic differentiated thyroid cancer. Molecular predictors of prevention of recurrence in hcc with. Patients and methods patients were stratified and randomly assigned to receive sunitinib 37. The sorafenib hepatocellular carcinoma hcc assessment randomized protocol sharp trial demonstrated that sorafenib improves overall survival and is. Determine the pharmacokinetics pk in patients with liver cancer. Find out if patients receiving sorafenib will live longer. In addition, the efficacy and the safety of sorafenib in clinical practice are addressed.
A phase 3 clinical trial comparing nivolumab and sorafenib as first. At asco 2007, results from the sharp trial 12 were presented, which showed efficacy of sorafenib in hepatocellular carcinoma. The sharp trial, conducted in 602 patients, was presented at last years asco meeting. The effects of lowering ldl cholesterol with simvastatin. The primary endpoint was progression free survival. In this trial involving patients with advanced hepatocellular carcinoma, sorafenib improved median survival by. Complete response under sorafenib in patients with. Clinical trials using sorafenib tosylate national cancer. Sorafenib for the treatment of advanced hepatocellular.
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