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: May 28, 2015
Last verified: May 2015
  Purpose

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).


Condition Intervention Phase
Carcinoma, Hepatocellular
Drug: Nexavar (Sorafenib, BAY43-9006)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Double-blind, Placebo-controlled Study of Sorafenib as Adjuvant Treatment for Hepatocellular Carcinoma After Surgical Resection or Local Ablation.

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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 ]

Enrollment: 1114
Study Start Date: August 2008
Study Completion Date: November 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib (Nexavar, BAY43-9006)
Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)
Drug: Nexavar (Sorafenib, BAY43-9006)
Sorafenib 400 mg twice daily (BID)
Placebo Comparator: Placebo
Participants received 2 tablets of placebo orally twice daily (BID)
Drug: Placebo
Placebo 2 tablets twice daily (BID)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00692770

  Show 234 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided by Bayer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00692770     History of Changes
Other Study ID Numbers: 12414, 2008-001087-36
Study First Received: June 5, 2008
Results First Received: November 24, 2014
Last Updated: May 28, 2015
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Chile: Instituto de Salud Pública de Chile
Mexico: Federal Commission for Sanitary Risks Protection
Austria: Ethikkommission
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Bulgaria: Bulgarian Drug Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: German Institute of Medical Documentation and Information
Greece: Ethics Committee
Italy: The Italian Medicines Agency
Romania: National Medicines Agency
Russia: Ethics Committee
Switzerland: Swissmedic
Sweden: Ethikkommission
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration
China: Food and Drug Administration
Japan: National Institute of Health Sciences
Hong Kong: Department of Health
Korea: Food and Drug Administration
New Zealand: Medsafe
Singapore: Health Sciences Authority
Taiwan: Department of Health
United States: Food and Drug Administration

Keywords provided by Bayer:
Hepatocellular carcinoma
Sorafenib
Adjuvant
Surgical resection
Ablation
Nexavar
Adjuvant therapy
Liver cancer
HCC
STORM

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015