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CheckMate040: 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

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT01658878
Collaborator
Ono Pharmaceutical Co. Ltd (Industry)
659
Enrollment
59
Locations
9
Arms
146
Anticipated Duration (Months)
11.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
Phase 1/Phase 2

Detailed Description

Study Classification: Pharmacokinetics/Pharmacodynamics

Study Design

Study Type:
Interventional
Actual Enrollment :
659 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 :
Oct 30, 2012
Anticipated Primary Completion Date :
Dec 28, 2023
Anticipated Study Completion Date :
Dec 29, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Non-infected: Nivolumab

Nivolumab intravenous solution on specific days

Biological: Nivolumab
Other Names:
  • BMS-936558

    		•
    Experimental: HCV-infected: Nivolumab

    Nivolumab intravenous solution on specific days

    Biological: Nivolumab
    Other Names:
  • BMS-936558

    		•
    Experimental: HBV-infected: Nivolumab

    Nivolumab intravenous solution on specific days

    Biological: Nivolumab
    Other Names:
  • BMS-936558

    		•
    Experimental: Nivolumab

    Nivolumab intravenous solution on specific days

    Biological: Nivolumab
    Other Names:
  • 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 Names:
  • BMS-936558

    • Drug: Ipilimumab
    Experimental: Child-Pugh B

    Nivolumab intravenous solution on specific days

    Biological: Nivolumab
    Other Names:
  • 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

    Outcome Measures

    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 [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 [100 days after last dose]

    3. Objective response rate (ORR) for Expansion phase of nivolumab [Approximately 6 months minimum follow-up]

    4. ORR for Nivolumab vs Sorafenib Cohort [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 [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 [100 days after last dose]

    7. ORR for Nivolumab plus Ipilimumab Combination Cohort [Approximately 6 months minimum follow-up]

    8. ORR for Child-Pugh B Cohort [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 [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 [100 days after last dose]

    11. ORR for Nivolumab plus Ipilimumab plus Cabozantinib Combination Cohort [Approximately 6 months minimum follow-up]

    Secondary Outcome Measures

    1. Complete response (CR) Rate [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) [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) [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) [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) [Approximately 9 years]

      It is defined from the date randomization to the date of the first objectively documented disease progression.

    6. TTP Rate [Approximately 9 years]

      It is defined as the K-M estimated proportion of subjects without progression at select milestones.

    7. Progression free survival (PFS) [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) [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) [100 days after last dose]

      It is defined as the K-M estimated proportion of subjects surviving at select milestones.

    10. PD-L1 expression [Approximately 6 months]

    11. Maximum observed serum concentration (Cmax) of nivolumab [Approximately 6 months]

    12. Time of maximum observed serum concentration (Tmax) of nivolumab [Approximately 6 months]

    13. Area under the serum concentration time curve in the dosing interval AUC(TAU) of nivolumab [Approximately 6 months]

    14. Serum concentration achieved at the end of dosing interval (trough concentration) (Ctrough) of nivolumab [Approximately 6 months]

    15. Serum concentration achieved at the end of the infusion (Ceoinf) of nivolumab [Approximately 6 months]

    16. Cmax at Cycle 3/ Cmax at Cycle 1 (AI_Cmax) of nivolumab [Approximately 6 months]

    17. AUC(TAU) at Cycle 3/ AUC(TAU) at Cycle 1 (AI_AUC) of nivolumab [Approximately 6 months]

    18. Effective T-Half of nivolumab [Approximately 6 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 USC Norris Comprehensive Cancer Center Los Angeles California United States 90033
    2 Georgetown University Medical Center Lombardi Cancer Center Washington District of Columbia United States 20007
    3 Sacred Heart Medical Group Pensacola Florida United States 32504
    4 Emory University Atlanta Georgia United States 30322
    5 Massachusetts General Hospital Boston Massachusetts United States 02114
    6 Univ Of Michigan Ann Arbor Michigan United States 48109-5331
    7 Hackensack University Medical Center Hackensack New Jersey United States 07601
    8 Saint Joseph's Regional Medical Center Paterson New Jersey United States 07503
    9 Providence Portland Medical Center Portland Oregon United States 97225
    10 Local Institution Houston Texas United States 77030
    11 QEII Health Sciences Centre Halifax Nova Scotia Canada B4H 2Y9
    12 University Health Network - Princess Margaret Cancer Centre Toronto Ontario Canada M5G 2M9
    13 CHUM Montreal Quebec Canada H2X 0A9
    14 Local Institution Angers France 49933
    15 Local Institution Creteil Cedex France 94010
    16 Local Institution Marseille Cedex 5 France 13385
    17 Local Institution Marseille Cedex 9 France 13273
    18 Local Institution Paris Cedex 13 France 75651
    19 Local Institution Reims Cedex France 51092
    20 Local Institution Vandoeuvre les Nancy France 54500
    21 Universitaetsklinikum Essen Essen Germany 45147
    22 Johann Wolfgang Goethe Universitaet Frankfurt Germany 60590
    23 Medizinische Hochschule Hannover Hannover Germany 30625
    24 Universitaetsklinik Heidelberg Heidelberg Germany 69120
    25 Local Institution Hong Kong Hong Kong
    26 Azienda Ospedaliera Di Bologna S. Orsola-Malpighi Bologna Italy 40138
    27 A.O.U. Careggi Firenze Italy 50134
    28 IRST Meldola Meldola (FC) Italy 47014
    29 Istituto Europeo Di Oncologia Milano Italy 20141
    30 Istituto Nazionale Tumori Napoli Italy 80131
    31 I.O.V. Istituto Oncologico Veneto Ircss Padova Italy 35128
    32 Istituto Clinico Humanitas Rozzano Italy 20089
    33 Local Institution Kashiwa-shi Chiba Japan 2778577
    34 Local Institution Kurume-shi Fukuoka Japan 8300011
    35 Local Institution Yokohama Kanagawa Japan 2320024
    36 Local Institution Kyoto-shi Kyoto Japan 6028566
    37 Local Institution Osaka-sayama-shi Osaka Japan 5898511
    38 Local Institution Saga Japan 8408571
    39 Local Institution Seoul Korea, Republic of 02841
    40 Local Institution Seoul Korea, Republic of 03080
    41 Local Institution Seoul Korea, Republic of 05505
    42 Local Institution Seoul Korea, Republic of 06351
    43 Local Institution San Juan Puerto Rico 00927
    44 Local Institution Singapore Singapore 119074
    45 Local Institution Singapore Singapore 169610
    46 Local Institution Singapore Singapore 308433
    47 Local Institution Barcelona Spain 08036
    48 Local Institution Madrid Spain 28007
    49 Local Institution Madrid Spain 28050
    50 Local Institution Pamplona Spain 31008
    51 Local Institution Taipei Taiwan 100
    52 Local Institution Taipei Taiwan 112201
    53 Local Institution Taoyuan Taiwan 333
    54 Local Institution London Greater London United Kingdom SE19RT
    55 Local Institution Manchester Greater Manchester United Kingdom M20 4BX
    56 Local Institution Glasgow Lanarkshire United Kingdom G12 0YN
    57 Local Institution Wirral Merseyside United Kingdom CH63 4JY
    58 Local Institution Birmingham West Midlands United Kingdom B15 2TH
    59 Local Institution London United Kingdom NW3 2QG

    Sponsors and Collaborators

    • Bristol-Myers Squibb
    • Ono Pharmaceutical Co. Ltd

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT01658878
    Other Study ID Numbers:
    • CA209-040
    • 2012-001514-42
    First Posted:
    Aug 7, 2012
    Last Update Posted:
    Dec 3, 2021
    Last Verified:
    Dec 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Hepatocellular
    Nivolumab
    Ipilimumab
    Sorafenib

    Study Results

    No Results Posted as of Dec 3, 2021