Clinical trial NCT00692770: Sorafenib as Adjuvant Treatment in the Prevention Of Recurrence of Hepatocellular Carcinoma (STORM)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Hepatocellular
Keywords: Hepatocellular carcinoma
Sorafenib
Adjuvant
Surgical resection
Ablation
Nexavar
Adjuvant therapy
Liver cancer
HCC
STORM
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2008-06-06
Enrollment: 1114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility 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

Primary outcomes:
measure: Recurrence Free Survival (RFS) by Independent Assessment
timeFrame: From randomization up to 4 years or until disease recurrence whichever came first
Secondary outcomes:
measure: Time to Recurrence (TTR) by Independent Assessment
timeFrame: From randomization up to 4 years or until disease recurrence whichever came first
measure: Overall Survival (OS)
timeFrame: From randomization of the first subject until 4 years later.
Other outcomes:
measure: Patient Reported Outcomes: Euroqol-5 Dimensions (EQ-5D) - Index Score
timeFrame: Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit
measure: Patient Reported Outcomes: Euroqol-5 Dimensions (EQ-5D) - Visual Analogue Scale (VAS) Score
timeFrame: Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit
measure: Patient Reported Outcomes: Functional Assessment of Cancer Therapy (FACT)- Hepatobiliary Subscale (HEP) Score
timeFrame: Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit
measure: Patient Reported Outcomes: Functional Assessment of Cancer Therapy (FACT)- General (G) Total Score
timeFrame: Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit
measure: The Correlation Between Plasma Biomarker Levels at Baseline With RFS to Determine Prognostic Value of Biomarkers - ANG-2
timeFrame: At Baseline
measure: The Correlation Between Plasma Biomarker Levels at Baseline With RFS to Determine Prognostic Value of Biomarkers - AFP
timeFrame: At Baseline
measure: The Correlation Between Plasma Biomarker Levels at Baseline With RFS to Determine Prognostic Value of Biomarkers - MET
timeFrame: At Baseline
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Indianapolis
country: United States
state: Indiana
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Burlington
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Minneapolis
country: United States
state: Minnesota
city: New York
country: United States
state: New York
city: Cleveland
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
state: Oregon
city: Pittsburgh
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Pilar
country: Argentina
state: Buenos Aires
city: Buenos Aires
country: Argentina
state: Ciudad Auton. De Buenos Aires
city: Rosario
country: Argentina
state: Santa Fe
city: Camperdown
country: Australia
state: New South Wales
city: Randwick
country: Australia
state: New South Wales
city: Brisbane
country: Australia
state: Queensland
city: Heidelberg
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Innsbruck
country: Austria
city: Linz
country: Austria
city: Wien
country: Austria
city: Bruxelles - Brussel
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Porto Alegre
country: Brazil
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
state: Sao Paulo
city: Sao Paulo
country: Brazil
city: Plovdiv
country: Bulgaria
city: Varna
country: Bulgaria
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Santiago de Chile
country: Chile
state: Santiago
city: Reñaca
country: Chile
state: Valparaíso
city: Guangzhou
country: China
state: Guangdong
city: Guangzhou
country: China
state: Guangdong
city: Guangzhou
country: China
state: Guangdong
city: Nanning
country: China
state: Guangxi
city: Wuhan
country: China
state: Hubei
city: Changsha
country: China
state: Hunan
city: Changsha
country: China
state: Hunan
city: Nanjing
country: China
state: Jiangsu
city: Xi'an
country: China
state: Shanxi
city: Xi'an
country: China
state: Shanxi
city: Xi'an
country: China
state: Shanxi
city: Chengdu
country: China
state: Sichuan
city: Chengdu
country: China
state: Sichuan
city: Beijing
country: China
city: Beijing
country: China
city: Beijing
country: China
city: Beijing
country: China
city: Beijng
country: China
city: Chongqing
country: China
city: Dalian
country: China
city: Hefei
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Tianjin
country: China
city: ANGERS cedex 09
country: France
city: Bondy
country: France
city: Bordeaux
country: France
city: Creteil
country: France
city: Lille
country: France
city: Lyon
country: France
city: Marseille
country: France
city: Nice
country: France
city: Paris
country: France
city: Paris
country: France
city: Rennes
country: France
city: Toulouse
country: France
city: Vandoeuvre-les-nancy
country: France
city: Villejuif
country: France
city: München
country: Germany
state: Bayern
city: München
country: Germany
state: Bayern
city: Regensburg
country: Germany
state: Bayern
city: Göttingen
country: Germany
state: Niedersachsen
city: Hannover
country: Germany
state: Niedersachsen
city: Aachen
country: Germany
state: Nordrhein-Westfalen
city: Düsseldorf
country: Germany
state: Nordrhein-Westfalen
city: Essen
country: Germany
state: Nordrhein-Westfalen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Mainz
country: Germany
state: Rheinland-Pfalz
city: Homburg/Saar
country: Germany
state: Saarland
city: Halle/Saale
country: Germany
state: Sachsen-Anhalt
city: Magdeburg
country: Germany
state: Sachsen-Anhalt
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Athens / Greece
country: Greece
city: Hong Kong
country: Hong Kong
city: Kwun Tong
country: Hong Kong
city: Shatin
country: Hong Kong
city: Benevento
country: Italy
state: Campania
city: Napoli
country: Italy
state: Campania
city: Napoli
country: Italy
state: Campania
city: Bologna
country: Italy
state: Emilia-Romagna
city: Modena
country: Italy
state: Emilia-Romagna
city: Roma
country: Italy
state: Lazio
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Torino
country: Italy
state: Piemonte
city: Bari
country: Italy
state: Puglia
city: Cagliari
country: Italy
state: Sardegna
city: Catania
country: Italy
state: Sicilia
city: Palermo
country: Italy
state: Sicilia
city: Padova
country: Italy
state: Veneto
city: Kashiwa-shi
country: Japan
state: Chiba
city: Kanazawa
country: Japan
state: Ishikawa
city: Yokohama-shi
country: Japan
state: Kanagawa
city: Osakasayama-shi
country: Japan
state: Osaka
city: Suita
country: Japan
state: Osaka
city: Bunkyo-ku
country: Japan
state: Tokyo
city: Chuo-ku
country: Japan
state: Tokyo
city: Itabashi-ku
country: Japan
state: Tokyo
city: Minato-ku
country: Japan
state: Tokyo
city: Shibuya-ku
country: Japan
state: Tokyo
city: Shinjuku-ku
country: Japan
state: Tokyo
city: Fukuoka
country: Japan
city: Kumamoto
country: Japan
city: Kyoto
country: Japan
city: Okayama
country: Japan
city: Osaka
country: Japan
city: Tokushima
country: Japan
city: Goyang-si
country: Korea, Republic of
state: Gyeonggido
city: Goyang-si
country: Korea, Republic of
state: Gyeonggido
city: Seoul
country: Korea, Republic of
state: Seoul Teugbyeolsi
city: Busan
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Jeollabuk-do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: México, D.F.
country: Mexico
state: Distrito Federal
city: Monterrey
country: Mexico
state: Nuevo Leon
city: México, D.F.
country: Mexico
city: Auckland
country: New Zealand
city: Coimbra
country: Portugal
city: Bucharest
country: Romania
city: Cluj-Napoca
country: Romania
city: Iasi
country: Romania
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Obninsk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Oviedo
country: Spain
state: Asturias
city: Sabadell
country: Spain
state: Barcelona
city: Cruces/Barakaldo
country: Spain
state: Bilbao
city: Barcelona
country: Spain
state: Catalunya
city: Majadahonda
country: Spain
state: Madrid
city: Badajoz
country: Spain
city: Barcelona
country: Spain
city: Córdoba
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Valladolid
country: Spain
city: Göteborg
country: Sweden
city: Stockholm
country: Sweden
city: Bern
country: Switzerland
city: Zürich
country: Switzerland
city: Changhua
country: Taiwan
city: Kaohsiung City
country: Taiwan
city: Kaohsung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Southampton
country: United Kingdom
state: Hampshire
city: Birmingham
country: United Kingdom
state: West Midlands
city: Leeds
country: United Kingdom
state: West Yorkshire
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, Cai J, Poon RT, Han KH, Tak WY, Lee HC, Song T, Roayaie S, Bolondi L, Lee KS, Makuuchi M, Souza F, Berre MA, Meinhardt G, Llovet JM; STORM investigators. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015 Oct;16(13):1344-54. doi: 10.1016/S1470-2045(15)00198-9. Epub 2015 Sep 8.
citation: Pinyol R, Montal R, Bassaganyas L, Sia D, Takayama T, Chau GY, Mazzaferro V, Roayaie S, Lee HC, Kokudo N, Zhang Z, Torrecilla S, Moeini A, Rodriguez-Carunchio L, Gane E, Verslype C, Croitoru AE, Cillo U, de la Mata M, Lupo L, Strasser S, Park JW, Camps J, Sole M, Thung SN, Villanueva A, Pena C, Meinhardt G, Bruix J, Llovet JM. Molecular predictors of prevention of recurrence in HCC with sorafenib as adjuvant treatment and prognostic factors in the phase 3 STORM trial. Gut. 2019 Jun;68(6):1065-1075. doi: 10.1136/gutjnl-2018-316408. Epub 2018 Aug 14.
citation: Bouattour M, Soubrane O, de Gramont A, Faivre S. Adjuvant therapies in advanced hepatocellular carcinoma: moving forward from the STORM. Trials. 2016 Nov 25;17(1):563. doi: 10.1186/s13063-016-1675-8.
citation: Kudo M. Adjuvant therapy after curative treatment for hepatocellular carcinoma. Oncology. 2011;81 Suppl 1:50-5. doi: 10.1159/000333259. Epub 2011 Dec 22.
citation: Printz C. Clinical trials of note. Sorafenib as adjuvant treatment in the prevention of disease recurrence in patients with hepatocellular carcinoma (HCC) (STORM). Cancer. 2009 Oct 15;115(20):4646. doi: 10.1002/cncr.24673. No abstract available.