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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00692770
First received: June 5, 2008
Last updated: December 12, 2014
Last verified: December 2014

June 5, 2008
December 12, 2014
August 2008
November 2013   (final data collection date for primary outcome measure)
Recurrence Free Survival (RFS) by Independent Assessment [ Time Frame: From randomization up to 4 years or until disease recurrence whichever came first ] [ Designated as safety issue: No ]

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.

Recurrence Free Survival [ Time Frame: approximately 40 months from first patient first visit ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00692770 on ClinicalTrials.gov Archive Site
  • Time to Recurrence (TTR) by Independent Assessment [ Time Frame: From randomization up to 4 years or until disease recurrence whichever came first ] [ Designated as safety issue: No ]
    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.
  • Overall Survival (OS) [ Time Frame: From randomization of the first subject until 4 years later. ] [ Designated as safety issue: No ]
    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.
  • Time to recurrence [ Time Frame: approximately 40 months from first patient first visit ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: approximately 80 months from first patient first visit ] [ Designated as safety issue: No ]
  • Patient-Reported Outcome (PRO) as assessed by FACT-Hep and EQ-5D questionnaire. [ Time Frame: approximately 40 months from first patient first visit ] [ Designated as safety issue: No ]
  • Evaluation of biomarkers. [ Time Frame: approximately 40 months from first patient first visit ] [ Designated as safety issue: No ]
  • Patient Reported Outcomes: Euroqol-5 Dimensions (EQ-5D) - Index Score [ Time Frame: Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit ] [ Designated as safety issue: No ]
    The EQ-5D is a generic quality of life preference based on a validated instrument used in cancer and in general population, with 2 parts: Index and Visual Analogue Scale. The EQ-5D Index is a descriptive system of the following health dimensions: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression. Subjects were asked to choose any one of the 3 response levels for each dimension: no problems, some problems, and severe problems. The 5 health dimensions were summarized into a single score, the EQ-5D Index score which ranged from -0.59 to 1 with higher scores representing better health states (0=death, 1= perfect health, and -0.59=a health state worse than death). A change of at least 0.10 to 0.12 points was considered a minimally important difference using Eastern Cooperative Oncology Group Performance Status as the anchor. The results on the Analysis of covariance of timeadjusted Area under curve for the EQ-5D index score were reported.
  • Patient Reported Outcomes: Euroqol-5 Dimensions (EQ-5D) - Visual Analogue Scale (VAS) Score [ Time Frame: Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit ] [ Designated as safety issue: No ]
    The EQ-5D is a generic quality of life preference based on a validated instrument used in cancer and in general population, with 2 parts: Index and Visual Analogue Scale. The EQ-5D VAS is a measure that represents health status as a single value. It is a 20-centimetre vertical graduated visual analogue scale with scores that ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). The respondent rated his/her current health state by drawing a line from the box marked 'your own health state today' to the appropriate point on the EQ-5D VAS. A 3-digit number (including leading zeros) was read off the scale from the point where the respondent's line crossed the scale, which was the EQ-5D VAS score. A change of at least 7 points on the VAS was considered as minimally important. The results on the ANCOVA analysis of time-adjusted AUC for the EQ-5D VAS score were reported.
  • Patient Reported Outcomes: Functional Assessment of Cancer Therapy (FACT)- Hepatobiliary Subscale (HEP) Score [ Time Frame: Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit ] [ Designated as safety issue: No ]
    The FACT-HEP is a 45 item, self-administered, multi-dimensional, psychometrically sound questionnaire used extensively in oncology clinical trials. FACT-HEP consisted of five subscales: Physical Well-Being (PWB), Social Well-Being (SWB), Emotional Well-Being (EWB), Functional Well-Being (FWB), and Hepatobiliary Cancer Subscale (HCS). The PWB, FWB, SWB and EWB were summed to form the FACTGeneral (FACT-G) total score. The FACT-G and HCS scores were summed to form the FACT-HEP total score. FACT-HEP scores ranged from 0 to 180 and the higher scores represented a better quality of life. Subjects responded to each item on a 5-point Likert-type scale ranging from 0 (not at all) to 4 (very much). The minimally important difference (MID) for the FACT-Hep total score was in the range of 8 to 9. The results on the ANCOVA analysis of time-adjusted AUC for the FACT-HEP score were reported.
  • Patient Reported Outcomes: Functional Assessment of Cancer Therapy (FACT)- General (G) Total Score [ Time Frame: Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit ] [ Designated as safety issue: No ]
    The PWB, FWB, SWB and EWB were summed to form the FACT-G total score. Subjects responded to each item on a 5-point Likert-type scale ranging from 0 (not at all) to 4 (very much). FACT-G scores ranged from 0 to 108 and the higher scores represented a better quality of life. The MID for the FACT-G total score was in the range of 6 to 7. The results on the ANCOVA analysis of time-adjusted AUC for the FACT-G score were reported.
  • Biomarker Analysis [ Time Frame: From randomization up to 4 years or until disease recurrence whichever came first ] [ Designated as safety issue: No ]
Not Provided
 
Sorafenib as Adjuvant Treatment in the Prevention Of Recurrence of Hepatocellular Carcinoma (STORM)
A Phase III Randomized, Double-blind, Placebo-controlled Study of Sorafenib as Adjuvant Treatment for Hepatocellular Carcinoma After Surgical Resection or Local Ablation.

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).

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Carcinoma, Hepatocellular
  • Drug: Nexavar (Sorafenib, BAY43-9006)
    Sorafenib 400 mg twice daily (BID)
  • Drug: Placebo
    Placebo 2 tablets twice daily (BID)
  • Experimental: Sorafenib (Nexavar, BAY43-9006)
    Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)
    Intervention: Drug: Nexavar (Sorafenib, BAY43-9006)
  • Placebo Comparator: Placebo
    Participants received 2 tablets of placebo orally twice daily (BID)
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1114
November 2014
November 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   China,   France,   Germany,   Greece,   Hong Kong,   Italy,   Japan,   Korea, Republic of,   Mexico,   New Zealand,   Peru,   Portugal,   Romania,   Russian Federation,   Singapore,   Spain,   Sweden,   Switzerland,   Taiwan,   United Kingdom
 
NCT00692770
12414, 2008-001087-36
Yes
Bayer
Bayer
Not Provided
Study Director: Bayer Study Director Bayer
Bayer
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP