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Trial record 1 of 1 for:    01658878
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An Immuno-therapy Study to Evaluate the Effectiveness, Safety and Tolerability of Nivolumab or Nivolumab in Combination With Other Agents in Patients With Advanced Liver Cancer (CheckMate040)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01658878
Recruitment Status : Active, not recruiting
First Posted : August 7, 2012
Last Update Posted : November 6, 2018
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:

The first part of the study is the Dose Escalation Phase designed to establish the safety of nivolumab at different dose levels for each of the three cohorts (uninfected hepatocellular carcinoma (HCC) subjects, hepatitis C virus (HCV)-infected HCC subjects, and hepatitis B virus (HBV)-infected subjects).

The second part of the study is the Expansion Phase designed to generate additional clinical data at specified doses for each of the 3 cohorts. A third cohort has been added in this study to compare the efficacy of nivolumab and sorafenib in the treatment of Advanced HCC. A fourth cohort will generate data on the safety and efficacy of the combination nivolumab plus ipilimumab in the treatment of Advanced HCC. In the fifth cohort, additional clinical data will be generated for Child-Pugh B subjects. A Cabozantinib Combination Cohort has been added to evaluate the safety and tolerability of nivolumab in combination with cabozantinib and nivolumab with ipilimumab in combination with cabozantinib.


Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Biological: Nivolumab Drug: Sorafenib Drug: Ipilimumab Drug: Cabozantinib Phase 1 Phase 2

Detailed Description:
Study Classification: Pharmacokinetics/Pharmacodynamics

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 620 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Dose-escalation, Open-label, Non-comparative Study of Nivolumab or Nivolumab in Combination With Ipilimumab in Advanced Hepatocellular Carcinoma Subjects With or Without Chronic Viral Hepatitis; and a Randomized, Open-label Study of Nivolumab vs Sorafenib in Advanced Hepatocellular Carcinoma Subjects Who Are Naive to Systemic Therapy
Actual Study Start Date : September 26, 2012
Estimated Primary Completion Date : March 31, 2019
Estimated Study Completion Date : December 26, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Non-infected: Nivolumab
Nivolumab intravenous solution on specific days
Biological: Nivolumab
Other Name: BMS-936558

Experimental: HCV-infected: Nivolumab
Nivolumab intravenous solution on specific days
Biological: Nivolumab
Other Name: BMS-936558

Experimental: HBV-infected: Nivolumab
Nivolumab intravenous solution on specific days
Biological: Nivolumab
Other Name: BMS-936558

Experimental: Nivolumab
Nivolumab intravenous solution on specific days
Biological: Nivolumab
Other Name: BMS-936558

Active Comparator: Sorafenib
Sorafenib tablets on specific days
Drug: Sorafenib
Experimental: Nivolumab plus Ipilimumab Combination
Nivolumab intravenous solution + Ipilimumab intravenous solution on specific days
Biological: Nivolumab
Other Name: BMS-936558

Drug: Ipilimumab
Experimental: Child-Pugh B
Nivolumab intravenous solution on specific days
Biological: Nivolumab
Other Name: BMS-936558

Experimental: Nivolumab plus Cabozantinib Combination
Nivolumab intravenous solution + cabozantinib oral tablets on specific days
Drug: Cabozantinib
Experimental: Nivolumab plus Ipilimumab plus Cabozantinib
Nivolumab intravenous solution + Ipilimumab intravenous solution + cabozantinib oral tablets on specific days
Drug: Cabozantinib



Primary Outcome Measures :
  1. Safety of nivolumab as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities [ Time Frame: 100 days after last dose ]
  2. Tolerability of nivolumab as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities [ Time Frame: 100 days after last dose ]
  3. Objective response rate (ORR) for Expansion phase of nivolumab [ Time Frame: Approximately 6 months minimum follow-up ]
  4. ORR for Nivolumab vs Sorafenib Cohort [ Time Frame: Approximately 6 months minimum follow-up ]
  5. Safety of nivolumab plus ipilimumab as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities [ Time Frame: 100 days after last dose ]
  6. Tolerability of nivolumab plus ipilimumab as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities [ Time Frame: 100 days after last dose ]
  7. ORR for Nivolumab plus Ipilimumab Combination Cohort [ Time Frame: Approximately 6 months minimum follow-up ]
  8. ORR for Child-Pugh B Cohort [ Time Frame: Approximately 6 months minimum follow-up ]
  9. Safety of nivolumab plus ipilimumab plus cabozantinib as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities [ Time Frame: 100 days after last dose ]
  10. Tolerability of nivolumab plus ipilimumab plus cabozantinib as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities [ Time Frame: 100 days after last dose ]
  11. ORR for Nivolumab plus Ipilimumab plus Cabozantinib Combination Cohort [ Time Frame: Approximately 6 months minimum follow-up ]

Secondary Outcome Measures :
  1. Complete response (CR) Rate [ Time Frame: Approximately 6 months minimum follow-up ]
    The proportion of subjects whose best overall response (BOR) is CR in the population of interest

  2. Disease control rate (DCR) [ Time Frame: Approximately 6 months minimum follow-up ]
    The proportion of subjects whose BOR is CR, Partial response (PR) or stable disease (SD) in the population of interest

  3. Duration of response (DOR) [ Time Frame: Approximately 9 years ]
    It is defined as time between the date of first radiographic documented objective response and the date of the radiographic disease progression.

  4. Time to response (TTR) [ Time Frame: Approximately 6 months ]
    It is defined as the time from randomization to the date of the first confirmed CR or PR for the 1L Nivolumab vs Sorafenib Cohort, and from the first dosing date of any study medication to the date of the first confirmed CR or PR for all other cohorts.

  5. Time to progression (TTP) [ Time Frame: Approximately 9 years ]
    It is defined from the date randomization to the date of the first objectively documented disease progression.

  6. TTP Rate [ Time Frame: Approximately 9 years ]
    It is defined as the K-M estimated proportion of subjects without progression at select milestones.

  7. Progression free survival (PFS) [ Time Frame: Approximately 9 years ]
    PFS is defined as the time from randomization date to the date of the first objectively documented tumor progression or death due to any cause

  8. Overall survival (OS) [ Time Frame: 100 days after last dose ]
    It is defined as the time from date of randomization to the date of death

  9. Overall survival rate (OSR) [ Time Frame: 100 days after last dose ]
    It is defined as the K-M estimated proportion of subjects surviving at select milestones.

  10. PD-L1 expression [ Time Frame: Approximately 6 months ]
  11. Maximum observed serum concentration (Cmax) of nivolumab [ Time Frame: Approximately 6 months ]
  12. Time of maximum observed serum concentration (Tmax) of nivolumab [ Time Frame: Approximately 6 months ]
  13. Area under the serum concentration time curve in the dosing interval AUC(TAU) of nivolumab [ Time Frame: Approximately 6 months ]
  14. Serum concentration achieved at the end of dosing interval (trough concentration) (Ctrough) of nivolumab [ Time Frame: Approximately 6 months ]
  15. Serum concentration achieved at the end of the infusion (Ceoinf) of nivolumab [ Time Frame: Approximately 6 months ]
  16. Cmax at Cycle 3/ Cmax at Cycle 1 (AI_Cmax) of nivolumab [ Time Frame: Approximately 6 months ]
  17. AUC(TAU) at Cycle 3/ AUC(TAU) at Cycle 1 (AI_AUC) of nivolumab [ Time Frame: Approximately 6 months ]
  18. Effective T-Half of nivolumab [ Time Frame: Approximately 6 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Inclusion Criteria:

  • Subjects of 18 years or older (men and women) with histologically confirmed advanced hepatocellular carcinoma, not eligible for surgical and/or locoregional therapies; or progressive disease after surgical and /or locoregional therapies
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
  • Dose Escalation Phase: Child-Pugh score of 7 points or less. Cohort 5: Child-Pugh Class B (B7-B8). For all other cohorts Child-Pugh score of 6 points or less

Exclusion Criteria:

  • History of autoimmune disease
  • Any prior or current clinically significant ascites
  • Any history of hepatic encephalopathy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01658878


  Hide Study Locations
Locations
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United States, California
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
United States, District of Columbia
Georgetown University Medical Center Lombardi Cancer Center
Washington, District of Columbia, United States, 20007
United States, Florida
Sacred Heart Medical Group
Pensacola, Florida, United States, 32504
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
Univ Of Michigan
Ann Arbor, Michigan, United States, 48109-5331
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Saint Joseph's Regional Medical Center
Paterson, New Jersey, United States, 07503
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Texas
The University Of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Canada, Nova Scotia
QEII Health Sciences Centre
Halifax, Nova Scotia, Canada, B4H 2Y9
Canada, Ontario
University Health Network - Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
CHUM
Montreal, Quebec, Canada, H2X 0A9
France
Local Institution
Angers, France, 49933
Local Institution
Creteil Cedex, France, 94010
Local Institution
Marseille Cedex 5, France, 13385
Local Institution
Marseille Cedex 9, France, 13273
Local Institution
Paris Cedex 13, France, 75651
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Reims Cedex, France, 51092
Local Institution
Vandoeuvre les Nancy, France, 54500
Germany
Universitaetsklinikum Essen
Essen, Germany, 45147
Johann Wolfgang Goethe Universitaet
Frankfurt, Germany, 60590
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Universitaetsklinik Heidelberg
Heidelberg, Germany, 69120
Hong Kong
Local Institution
Hong Kong, Hong Kong
Italy
Azienda Ospedaliera Di Bologna S. Orsola-Malpighi
Bologna, Italy, 40138
A.O.U. Careggi
Firenze, Italy, 50134
Istituto Romagnolo Per Lo Studio E La Cura Dei Tumori
Meldola (FC), Italy, 47014
Istituto Europeo Di Oncologia
Milano, Italy, 20141
Istituto Nazionale Tumori
Napoli, Italy, 80131
I.O.V. Istituto Oncologico Veneto Ircss
Padova, Italy, Padova
Istituto Clinico Humanitas
Rozzano, Italy, 20089
Japan
Local Institution
Kashiwa-shi, Chiba, Japan, 2778577
Local Institution
Kurume-shi, Fukuoka, Japan, 8300011
Local Institution
Yokohama, Kanagawa, Japan, 2320024
Local Institution
Kyoto-shi, Kyoto, Japan, 6028566
Local Institution
Osaka-sayama-shi, Osaka, Japan, 5898511
Local Institution
Saga, Japan, 8408571
Korea, Republic of
Local Institution
Seoul, Korea, Republic of, 02841
Local Institution
Seoul, Korea, Republic of, 03080
Local Institution
Seoul, Korea, Republic of, 05505
Local Institution
Seoul, Korea, Republic of, 06351
Puerto Rico
Local Institution
San Juan, Puerto Rico, 00927
Singapore
Local Institution
Singapore, Singapore, 119074
Local Institution
Singapore, Singapore, 169610
Local Institution
Singapore, Singapore, 308433
Spain
Local Institution
Barcelona, Spain, 08036
Local Institution
Madrid, Spain, 28007
Local Institution
Madrid, Spain, 28050
Clinica Universitaria De Navarra
Pamplona, Spain, 31008
Taiwan
Local Institution
Taipei, Taiwan, 100
Local Institution
Taipei, Taiwan, 112
Local Institution
Taoyuan, Taiwan, 333
United Kingdom
Local Institution
London, Greater London, United Kingdom, SE19RT
Local Institution
Manchester, Greater Manchester, United Kingdom, M20 4BX
Local Institution
Glasgow, Lanarkshire, United Kingdom, G12 0YN
Local Institution
Wirral, Merseyside, United Kingdom, CH63 4JY
Local Institution
Birmingham, WEST Midlands, United Kingdom, B15 2TH
Local Institution
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01658878     History of Changes
Other Study ID Numbers: CA209-040
2012-001514-42 ( EudraCT Number )
First Posted: August 7, 2012    Key Record Dates
Last Update Posted: November 6, 2018
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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