Sorafenib as Adjuvant Treatment in the Prevention Of Recurrence of Hepatocellular Carcinoma (STORM)

Study Overview
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Brief Summary
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To evaluate efficacy and safety of sorafenib versus placebo in the adjuvant treatment of Hepatocellular Carcinoma (HCC) after potentially curative treatment (surgical resection or local ablation).

Official Title
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A Phase III Randomized, Double-blind, Placebo-controlled Study of Sorafenib as Adjuvant Treatment for Hepatocellular Carcinoma After Surgical Resection or Local Ablation.

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: Nexavar (Sorafenib, BAY43-9006)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have undergone surgical resection or local ablation (PEI or percutaneous or intraoperative RFA) for treatment of HCC with curative intent within 4 months from staging to potentially curative treatment. A maximum of 2 local ablation courses may be administered during this time period. At least 3 weeks (21 days) but no more than 7 weeks (49 days), from resection or last local ablation course, to CT/MRI scan date Male or female subjects >/= 18 years of age Confirmation of CR (absence of residual tumor after curative treatment), on the eligibility scan by independent radiological review. For subjects undergoing surgical resection pathology proven complete removal of tumor. Intermediate or High Risk of recurrence as assessed by tumor characteristics. Child-Pugh score 5 -7 points. A Child-Pugh score of 7 points is allowed only in the absence of ascites. ECOG Performance Status of 0. Adequate bone marrow, liver and renal function Exclusion Criteria: Recurrent HCC Child-Pugh score 7 points with presence of ascites. Low risk of recurrence after curative treatment History of cardiovascular disease History of HIV infection Active clinically serious infections (> grade 2 NCI-CTCAE version 3.0) Subjects with seizure disorder requiring medication (such as steroids or anti-epileptics) Subjects with evidence or history of bleeding diathesis Subjects undergoing renal dialysis Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry as defined by the signing of informed consent.. Uncontrolled ascites (defined as not easily controlled with diuretic treatment) Encephalopathy History of GI bleeding within 30 days of randomization. Subjects with a history of esophageal varices bleeding which has not been followed by effective therapy and/or treatment to prevent bleeding recurrence. Prior anti cancer therapy for treatment of HCC (including sorafenib or any other molecular therapy) is excluded. Major surgery within 4 weeks of start of study as defined by the signing of informed consent, except for surgical resection or local ablation of HCC. Investigational drug therapy outside of this trial during or within 4 weeks of study entry, as defined by the signing of informed consent. Liver transplantation, this includes patients on a transplant list with the intention to transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib (Nexavar, BAY43-9006)<br>Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) | Drug: Nexavar (Sorafenib, BAY43-9006)<br>* Sorafenib 400 mg twice daily (BID)<br>|
| Placebo Comparator: Placebo<br>Participants received 2 tablets of placebo orally twice daily (BID) | Drug: Placebo<br>* Placebo 2 tablets twice daily (BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence Free Survival (RFS) by Independent Assessment | Disease recurrence of HCC (intra or extra hepatic) was defined as the appearance of a new intrahepatic lesions fulfilling the American Association for the Study of Liver Diseases (AASLD) criteria of diagnosis of HCC or a new extra-hepatic lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.0. In addition to investigator assessment, all images were reviewed by an independent panel of radiologists. The calculation of the RFS was based on the independent evaluation of the scans. RFS was defined as the time from randomization to the first documented disease recurrence by independent radiological assessment or death due to any cause whichever occurred first. For subjects who had not recurred or died at the time of analysis, RFS was censored at their last date of evaluable scan before drop-out for any other reason than recurrence or death. | From randomization up to 4 years or until disease recurrence whichever came first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Recurrence (TTR) by Independent Assessment | TTR was defined as the time from randomization to the first documented disease recurrence by independent radiological assessment. For subjects who had not recurred at the time of analysis, TTR was censored at their last date of evaluable scan before withdrawal for any other reason than recurrence. NA in the reported data indicates values could not be estimated due to censored data. | From randomization up to 4 years or until disease recurrence whichever came first | 
| Overall Survival (OS) | OS was defined as the time from randomization to date of death due to any cause. OS for subjects alive at the time of analysis was censored at their last date of contact. NA in the reported data indicates values could not be estimated due to censored data. | From randomization of the first subject until 4 years later. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, Hepatocellular carcinoma, Sorafenib, Adjuvant, Surgical resection, Ablation, Nexavar, Adjuvant therapy, Liver cancer, STORM