First Line Hepato Cellular Carcinoma (HCC) (BRISK FL)

A Randomized, Double-blind, Multi-center Phase III Study of Brivanib Versus Sorafenib as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma

The purpose of this study is to compare the overall survival of brivanib versus sorafenib in subjects with advanced HCC who have not received prior systemic therapy.

Study Overview

• Status: Completed
• Conditions: Hepato Cellular Carcinoma (HCC)
• Intervention / Treatment: Drug: Brivanib; Drug: Placebo; Drug: Placebo; Drug: Sorafenib

• Study Type: Interventional
• Enrollment (Actual): 1714
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1181ACH
    • Local Institution
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, 1221
      • Local Institution
    • Capital Federal, Buenos Aires, Argentina, C1264AAA
      • Local Institution
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Local Institution
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Local Institution
    • Concord, New South Wales, Australia, 2139
      • Local Institution
    • Westmead Nsw, New South Wales, Australia, 2145
      • Local Institution
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Local Institution
    • Prahan, Victoria, Australia, 3004
      • Local Institution
• Belgium
  • Liege, Belgium, 4000
    • Local Institution
• Brazil
  • Sao Paulo, Brazil, 01323-010
    • Local Institution
  • Bahia
    • Salvador, Bahia, Brazil, 41950-610
      • Local Institution
    • Salvador - Ba, Bahia, Brazil, 40050-410
      • Local Institution
  • Ceara
    • Fortaleza, Ceara, Brazil, 60430-230
      • Local Institution
  • Goias
    • Goiania, Goias, Brazil, 74075-040
      • Local Institution
  • Minas Gerais
    • Divinopolis, Minas Gerais, Brazil, 35500-249
      • Local Institution
  • Parana
    • Curitiba, Parana, Brazil, 81520-060
      • Local Institution
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90050-170
      • Local Institution
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Local Institution
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Local Institution
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784-400
      • Local Institution
    • Jau, Sao Paulo, Brazil, 17210-080
      • Local Institution
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Local Institution
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Local Institution
  • Ontario
    • London, Ontario, Canada, N6A A5
      • Local Institution
  • Quebec
    • Montreal, Quebec, Canada, H2X 3J4
      • Local Institution
• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Local Institution
    • Beijing, Beijing, China, 100034
      • Local Institution
    • Beijing, Beijing, China, 100071
      • Local Institution
  • Chongqing
    • Chongqing, Chongqing, China, 400038
      • Local Institution
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Local Institution
    • Guanzhou, Guangdong, China, 510010
      • Local Institution
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Local Institution
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Local Institution
  • Hunan
    • Changsha, Hunan, China, 410008
      • Local Institution
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Local Institution
    • Nanjing, Jiangsu, China, 210000
      • Local Institution
    • Nanjing, Jiangsu, China, 210002
      • Local Institution
    • Nanjing, Jiangsu, China, 210008
      • Local Institution
    • Suzhou, Jiangsu, China, 215006
      • Local Institution
  • Liaoning
    • Dalian, Liaoning, China, 116011
      • Local Institution
  • Shaanxi
    • Xi An, Shaanxi, China, 710032
      • Local Institution
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Local Institution
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Local Institution
  • Zhejiang
    • Hangzhou, Zhejiang, China, 130016
      • Local Institution
• Czech Republic
  • Brno, Czech Republic, 656 53
    • Local Institution
  • Prague 5, Czech Republic, 150 06
    • Local Institution
  • Praha 2, Czech Republic, 128 08
    • Local Institution
• France
  • Bordeaux, France, 33075
    • Local Institution
  • Clichy Cedex, France, 92118
    • Local Institution
  • Creteil Cedex, France, 94010
    • Local Institution
  • Grenoble Cedex 09, France, 38043
    • Local Institution
  • Lille, France, 59037
    • Local Institution
  • Lyon Cedex 04, France, 69317
    • Local Institution
  • Marseille Cedex 05, France, 13385
    • Local Institution
  • Marseille Cedex 9, France, 13009
    • Local Institution
  • Paris, France, 75012
    • Local Institution
  • Paris, France, 75013
    • Local Institution
  • Paris, France, 75020
    • Local Institution
  • Rennes, France, 35042
    • Local Institution
  • Vandoeuvre Cedex, France, 54511
    • Local Institution
• Germany
  • Berlin, Germany, 13353
    • Local Institution
  • Halle, Germany, 06120
    • Local Institution
  • Hamburg, Germany, 20246
    • Local Institution
  • Magdeburg, Germany, 39120
    • Local Institution
  • Ulm, Germany, 89081
    • Local Institution
• Hong Kong
  • Hong Kong, Hong Kong, 8525
    • Local Institution
  • Shatin, Hong Kong, 8520
    • Local Institution
• India
  • Ahmedabad, India, 380009
    • Local Institution
  • Chennai, India, 600006
    • Local Institution
  • Coimbatore, India, 641037
    • Local Institution
  • Hyderabad, India, 500024
    • Local Institution
  • Kolkata, India, 700 053
    • Local Institution
  • Kolkata, India, 700054
    • Local Institution
  • Mumbai, India, 400012
    • Local Institution
  • Mumbai, India, 400036
    • Local Institution
  • New Delhi, India, 110 070
    • Local Institution
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500082
      • Local Institution
  • Kerala
    • Kochi, Kerala, India, 682304
      • Local Institution
    • Trivandrum, Kerala, India, 695011
      • Local Institution
  • Maharashtra
    • Pune, Maharashtra, India, 411001
      • Local Institution
• Italy
  • Milano, Italy, 20122
    • Local Institution
  • Milano, Italy, 20141
    • Local Institution
  • Napoli, Italy, 80131
    • Local Institution
  • Pisa, Italy, 56124
    • Local Institution
  • Roma, Italy, 00168
    • Local Institution
  • Torrette -Ancona, Italy, 60020
    • Local Institution
• Japan
  • Nishinomiya-shi, Japan, 6638501
    • Local Institution
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-0882
      • Local Institution
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060-0033
      • Local Institution
  • Ishikawa
    • Kanazawa-Shi, Ishikawa, Japan, 9208641
      • Local Institution
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan, 2138587
      • Local Institution
    • Yokohama, Kanagawa, Japan, 232-0024
      • Local Institution
  • MIE
    • Tsu-shi, MIE, Japan, 5148507
      • Local Institution
  • Okayama
    • Okayama-shi, Okayama, Japan, 7000082
      • Local Institution
  • Osaka
    • Higashinari-ku, Osaka, Japan, 5378511
      • Local Institution
    • Osaka-Sayama City, Osaka, Japan, 5890014
      • Local Institution
    • Osaka-shi, Osaka, Japan, 534-0021
      • Local Institution
    • Osaka-shi, Osaka, Japan, 5438555
      • Local Institution
    • Osaka-shi, Osaka, Japan, 5458586
      • Local Institution
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Local Institution
  • Tokyo
    • Chuo-Ku, Tokyo, Japan, 104-0045
      • Local Institution
    • Minato-ku, Tokyo, Japan, 105-0001
      • Local Institution
    • Musashino-shi, Tokyo, Japan, 180-0023
      • Local Institution
  • Yamaguchi
    • Shimonoseki-shi, Yamaguchi, Japan, 7500061
      • Local Institution
• Korea, Republic of
  • Busan, Korea, Republic of, 609-735
    • Local Institution
  • Daegu, Korea, Republic of, 700-721
    • Local Institution
  • Gyeonggi-do, Korea, Republic of, 410-769
    • Local Institution
  • Kyunggi-do, Korea, Republic of, 463-707
    • Local Institution
  • Seoul, Korea, Republic of, 110-744
    • Local Institution
  • Seoul, Korea, Republic of, 120-752
    • Local Institution
  • Seoul, Korea, Republic of, 135-710
    • Local Institution
  • Seoul, Korea, Republic of, 137-040
    • Local Institution
  • Seoul, Korea, Republic of, 138-736
    • Local Institution
• Mexico
  • Aguascalientes, Mexico, 20234
    • Local Institution
  • Distrito Federal, Mexico, 06760
    • Local Institution
  • Distrito Federal
    • D.f., Distrito Federal, Mexico, 06720
      • Local Institution
    • D.f., Distrito Federal, Mexico, 14140
      • Local Institution
    • Mexico City, Distrito Federal, Mexico, 06726
      • Local Institution
    • Tlalpan, Distrito Federal, Mexico, 14000
      • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64710
      • Local Institution
• Poland
  • Gdansk, Poland, 80952
    • Local Institution
  • Gliwice, Poland, 44-101
    • Local Institution
  • Krakow, Poland, 31-501
    • Local Institution
  • Warszawa, Poland, 02-781
    • Local Institution
• Puerto Rico
  • San Juan, Puerto Rico, 00910
    • Local Institution
• Russian Federation
  • Moscow, Russian Federation, 115 478
    • Local Institution
  • Moscow, Russian Federation, 115998
    • Local Institution
  • Moscow, Russian Federation, 119992
    • Local Institution
  • Moscow, Russian Federation, 125367
    • Local Institution
• South Africa
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0002
      • Local Institution
  • Kwa Zulu Natal
    • Durban, Kwa Zulu Natal, South Africa, 4091
      • Local Institution
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7570
      • Local Institution
    • Observatory, Cape Town, Western Cape, South Africa, 7925
      • Local Institution
    • Rondebosch, Western Cape, South Africa, 7700
      • Local Institution
• Spain
  • Alicante, Spain, 03010
    • Local Institution
  • Barcelona, Spain, 08208
    • Local Institution
  • A Coruna
    • Santiago De Compostela, A Coruna, Spain, 15706
      • Local Institution
• Sweden
  • Stockholm, Sweden, 141 86
    • Local Institution
  • Uppsala, Sweden, 751 85
    • Local Institution
• Taiwan
  • Changhua, Taiwan, 500
    • Local Institution
  • Kaohsiung, Taiwan, 833
    • Local Institution
  • Taichung, Taiwan, 404
    • Local Institution
  • Tainan R.O.C., Taiwan, 70403
    • Local Institution
  • Taipei, Taiwan, 100
    • Local Institution
  • Taipei, Taiwan, 112
    • Local Institution
  • Taoyuan, Taiwan, 333
    • Local Institution
• Thailand
  • Bangkok, Thailand, 10400
    • Local Institution
  • Bangkok, Thailand, 10700
    • Local Institution
• Turkey
  • Ankara, Turkey, 06460
    • Local Institution
  • Antalya, Turkey, 07070
    • Local Institution
  • Istanbul, Turkey
    • Local Institution
  • Izmir, Turkey, 35100
    • Local Institution
  • Kayseri, Turkey, 38039
    • Local Institution
• United Kingdom
  • Avon
    • Bristol, Avon, United Kingdom, BS2 8ED
      • Local Institution
  • Greater London
    • London, Greater London, United Kingdom, NW3 2QG
      • Local Institution
    • London, Greater London, United Kingdom, SE5 9RS
      • Local Institution
    • London, Greater London, United Kingdom, W12 0HS
      • Local Institution
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • Local Institution
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TT
      • Local Institution
  • Yorkshire
    • Leeds, Yorkshire, United Kingdom, LS9 7TF
      • Local Institution
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Univ Of Ark For Med Sci
  • California
    • Downey, California, United States, 90241
      • Agajanian Institute Of Hematology And Oncology
    • San Diego, California, United States, 92123
      • Sharp Clinical Oncology Research
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA CT Healthcare System
  • Florida
    • Lake Worth, Florida, United States, 33467
      • Medical Specialists Of Palm Beaches
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • 3912 Taubman Center
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson Univ.
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire DVAMC
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

• Histologic or cytologic confirmed diagnosis of HCC.
• Advanced HCC: disease not eligible for surgical and/or locoregional therapies OR progressive disease after surgical and/or locoregional therapies
• Child-Pugh Class A
• ECOG performance status 0-1
• Adequate hematologic, hepatic, and renal function

Exclusion Criteria:

• Prior use of any systemic anti-cancer chemotherapy, immunotherapy or molecular targeted agents for HCC
• History of active cardiac disease
• Thrombotic or embolic events within the past 6 months (except HCC tumor thrombus)
• Any other hemorrhage/bleeding event >= CTCAE Grade 3 within 8 weeks except for esophageal or gastric varices
• Inability to swallow tablets or untreated malabsorption syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Brivanib	Drug: Brivanib; Tablets, Oral, 800 mg, Once Daily, Until disease progression or unacceptable toxicity; Other Names: BMS-582664; Drug: Placebo; Capsules, Oral, twice Daily, Until disease progression or unacceptable toxicity; Drug: Placebo; Tablets, Oral, Once Daily, Until disease progression or unacceptable toxicity
Active Comparator: Sorafenib	Drug: Placebo; Capsules, Oral, twice Daily, Until disease progression or unacceptable toxicity; Drug: Placebo; Tablets, Oral, Once Daily, Until disease progression or unacceptable toxicity; Drug: Sorafenib; Capsules, Oral, 800 mg, twice daily, Until disease progression or unacceptable toxicity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To compare the overall survival of brivanib versus sorafenib in subjects with advanced HCC who have not received prior systemic treatment	Survival will be assessed continuously

Secondary Outcome Measures

Outcome Measure	Time Frame
To compare the time to progression (TTP) (investigator assessed using modified RECIST criteria for HCC	Every 6 weeks
To compare the investigator assessed objective response rate (ORR) and disease control rate (DCR) using modified RECIST criteria for HCC	Every 6 weeks
To determine duration of response, duration of disease control, and time to response (TTR)	Every 6 weeks
To assess the safety profile of brivanib and sorafenib	Every 6 weeks
To explore PK and exposure-response in the study population	Every 6 weeks
To compare time to symptomatic progression	Every 6 weeks
To compare health-related quality of life	Every 6 weeks

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Kolamunnage-Dona R, Berhane S, Potts H, Williams EH, Tanner J, Janowitz T, Hoare M, Johnson P. Sorafenib is associated with a reduced rate of tumour growth and liver function deterioration in HCV-induced hepatocellular carcinoma. J Hepatol. 2021 Oct;75(4):879-887. doi: 10.1016/j.jhep.2021.05.015. Epub 2021 May 27.
• Johnson PJ, Qin S, Park JW, Poon RT, Raoul JL, Philip PA, Hsu CH, Hu TH, Heo J, Xu J, Lu L, Chao Y, Boucher E, Han KH, Paik SW, Robles-Avina J, Kudo M, Yan L, Sobhonslidsuk A, Komov D, Decaens T, Tak WY, Jeng LB, Liu D, Ezzeddine R, Walters I, Cheng AL. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study. J Clin Oncol. 2013 Oct 1;31(28):3517-24. doi: 10.1200/JCO.2012.48.4410. Epub 2013 Aug 26.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: March 9, 2009
• First Submitted That Met QC Criteria: March 9, 2009
• First Posted (Estimate): March 10, 2009

Study Record Updates

• Last Update Posted (Estimate): October 17, 2016
• Last Update Submitted That Met QC Criteria: October 14, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: CA182-033; EUDRACT # 2008-003533-24

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No