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An Investigational Immuno-therapy Study of Nivolumab Compared to Sorafenib as a First Treatment in Patients With Advanced Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT02576509
Recruitment Status : Active, not recruiting
First Posted : October 15, 2015
Results First Posted : June 26, 2020
Last Update Posted : February 26, 2021
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:
The purpose of this study is to determine if nivolumab or sorafenib is more effective in the treatment of Advanced Hepatocellular Carcinoma.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Nivolumab Drug: Sorafenib Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 743 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Multi-center Phase III Study of Nivolumab Versus Sorafenib as First-Line Treatment in Patients With Advanced Hepatocellular Carcinoma (CheckMate 459: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 459)
Actual Study Start Date : December 7, 2015
Actual Primary Completion Date : May 30, 2019
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nivolumab
Nivolumab specified dose on specified days
Drug: Nivolumab
Active Comparator: Sorafenib
Sorafenib specified dose on specified days
Drug: Sorafenib



Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: time from the date of randomization to the date of death due to any cause, assessed up to June 2019 (approximately 41 months) ]

    OS is defined as the time from the date of randomization to the date of death due to any cause in all randomized participants. Participants who are alive will be censored at the last known alive dates.

    Based on Kaplan-Meier Estimates.



Secondary Outcome Measures :
  1. Objective Response Rate (ORR) Per BICR RECIST 1.1 [ Time Frame: the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months) ]

    ORR is defined as the proportion of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR is defined as the best response designation, as determined based on BICR-assessed tumor response according to RECIST 1.1, recorded between the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent anti-cancer therapy, all available response designations will contribute to the BOR determination. For a BOR of CR or PR, the initial response assessment must be confirmed by a consecutive assessment no less than 4 weeks (28 days) later.

    Estimate of (Nivolumab - Sorafenib) is based on CMH method of weighting, stratified by stratification factors


  2. Progression-Free Survival (PFS) [ Time Frame: time from the date of randomization to the date of the first objectively documented tumor progression or death, assessed up to May 2019 (approximately 40 months) ]
    PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by BICR according to RECIST 1.1 or death due to any cause in all randomized participants. Participants who die without a reported prior progression and without initiation of subsequent anti-cancer therapy will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment. Participants who did not have baseline tumor assessment will be censored on the date they were randomized. Participants who did not have any on study tumor assessments and did not die will be censored on the date they were randomized. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to subsequent anti-cancer therapy.

  3. Efficacy Based on PD-L1 Expression - OS and PFS [ Time Frame: the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months) ]

    PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as:

    Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling.

    Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate).

    PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression:

    • PD-L1 > X %: ≥ X % PD-L1 expression
    • PD-L1 < X %: < X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored.

    Confidence interval based on the Clopper and Pearson method.


  4. Efficacy Based on PD-L1 Expression - ORR [ Time Frame: the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months) ]

    PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as:

    Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling.

    Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate).

    PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression:

    • PD-L1 > X %: ≥ X % PD-L1 expression
    • PD-L1 < X %: < X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored.

    Confidence interval based on the Clopper and Pearson method.




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:

  • Histologically confirmed advanced hepatocellular carcinoma, not eligible for surgical and/or locoregional therapies; or progressive disease after surgical and /or locoregional therapies
  • Locoregional therapy for hepatocellular carcinoma (HCC) must be completed at least 4 weeks prior to the baseline scan
  • Child-Pugh Class A
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

Exclusion Criteria:

  • Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
  • Prior liver transplant
  • Active, known, or suspected autoimmune disease

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): NCT02576509


Locations
Show Show 134 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Investigators
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Study Director: Bristol Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Statistical Analysis Plan  [PDF] July 2, 2018
Study Protocol  [PDF] January 15, 2019

Additional Information:
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02576509    
Other Study ID Numbers: CA209-459
First Posted: October 15, 2015    Key Record Dates
Results First Posted: June 26, 2020
Last Update Posted: February 26, 2021
Last Verified: February 2021
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
Sorafenib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action