Clinical Trials /

Feasibility and Efficacy of Perioperative Nivolumab With or Without Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma (HCC)

NCT04658147

Description:

The purpose of this study is to determine the safety and tolerability of neoadjuvant/adjuvant Nivolumab or Nivolumab plus Relatlimab in patients with HCC.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Feasibility and Efficacy of Perioperative Nivolumab With or Without Neoadjuvant Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma (HCC)
  • Official Title: Feasibility and Efficacy of Perioperative Nivolumab With or Without Neoadjuvant Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma (HCC)

Clinical Trial IDs

  • ORG STUDY ID: J20121
  • SECONDARY ID: IRB00246739
  • NCT ID: NCT04658147

Conditions

  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
NivolumabOPDIVO™, BMS 936558, MDX1106, ONO-4538Arm A - Nivolumab
RelatlimabBMS-986016, BMS-986016-01, Anti-LAG-3Arm B - Nivolumab and Relatlimab

Purpose

The purpose of this study is to determine the safety and tolerability of neoadjuvant/adjuvant Nivolumab or Nivolumab plus Relatlimab in patients with HCC.

Trial Arms

NameTypeDescriptionInterventions
Arm A - NivolumabExperimentalParticipants receive Nivolumab only.
  • Nivolumab
Arm B - Nivolumab and RelatlimabExperimentalParticipants receive Nivolumab and Relatlimab.
  • Nivolumab
  • Relatlimab

Eligibility Criteria

        Inclusion Criteria:

        • Technically resectable HCC as defined by:

          -  HCC may be diagnosed pathologically, or noninvasively by the American Association for
             the Study of Liver Diseases (AASLD) criteria or the Organ Procurement and Transplant
             Network (OPTN) Obligatory Diagnostic Criteria for Hepatocellular Carcinoma (HCC).

        No extrahepatic spread, no nodal disease, and no bilateral left and right branch portal
        vein involvement.

          -  Measurable disease per RECIST 1.1 as determined by the investigator.

          -  Age ≥ 18 years old on the day of consent.

          -  ECOG performance status ≤1 or Karnofsky ≥80.

          -  Patients must have adequate organ and marrow function defined by study-specified
             laboratory tests prior to initial study drug.

          -  Patients must have adequate liver remnant and function.

          -  Antiviral therapy per local standard of care for hepatitis B.

          -  LVEF assessment with documented LVEF ≥ 50% by either TTE or MUGA (TTE preferred)
             within 6 months from first study drug administration.

          -  Woman of child-bearing potential must have a negative pregnancy test.

          -  Must use acceptable form of birth control while on study.

          -  Ability to understand and willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Fibrolamellar carcinoma or mixed HCC.

          -  Receiving, or previously received, any systemic chemotherapy, or investigational agent
             for HCC.

          -  Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2,
             anti-CTLA4, or anti-Lag-3 antibodies.

          -  Has a known additional malignancy that is expected to require active treatment within
             two years, or is likely to be life-limiting in the opinion of the treating
             investigator. Superficial bladder cancer, non-melanoma skin cancers, or low grade
             prostate cancer not requiring therapy would not exclude participation in this trial.

          -  History of HIV infection.

          -  Active co-infection with HBV and HDV.

          -  Has a diagnosis of immunodeficiency, or is receiving systemic steroid therapy.

          -  Prior tissue or organ allograft or allogeneic bone marrow transplantation.

          -  History of any autoimmune disease requiring systemic treatment within the past 2
             years.

          -  Systemic or topical corticosteroids at immunosuppressive doses (> 10 mg/day of
             prednisone or equivalent).

          -  Confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year
             prior to informed consent.

          -  Uncontrolled intercurrent illness.•

          -  Uncontrolled or significant cardiovascular disease.

          -  Significant heart disease.

          -  Moderate or severe ascites.

          -  Known or suspected hypersensitivity to study treatment.

          -  Are pregnant or breastfeeding.

          -  WOCBP and men with female partners (WOCBP) who are not willing to use contraception.

          -  Unable to have blood drawn.

          -  Any other sound medical, psychiatric, and/or social reason as determined by the
             Investigator.

          -  Any illicit drugs or other substance abuse.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients who complete pre-op treatment and proceed to surgery
Time Frame:4 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of participants experiencing study drug-related toxicities
Time Frame:4 years
Safety Issue:
Description:Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.
Measure:Percentage of participants who obtain R0 resection
Time Frame:8 weeks
Safety Issue:
Description:
Measure:Percentage of evaluable patients who obtain a pathologic complete response (pCR) or major pathologic response (MPR)
Time Frame:8 weeks
Safety Issue:
Description:
Measure:Objective response rate (ORR) at 8 weeks
Time Frame:8 weeks
Safety Issue:
Description:ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
Measure:Overall survival (OS) at 12 months
Time Frame:12 months
Safety Issue:
Description:OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
Measure:Overall survival (OS) at 18 months
Time Frame:18 months
Safety Issue:
Description:OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
Measure:Overall survival (OS) at 3 years
Time Frame:3 years
Safety Issue:
Description:OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
Measure:Overall survival (OS) at 5 years
Time Frame:5 years
Safety Issue:
Description:OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
Measure:Disease free survival (DFS) at 12 months
Time Frame:12 months
Safety Issue:
Description:Number of months from the date of first treatment until disease recurrence at 12 months. Estimation based on the Kaplan-Meier curve.
Measure:Disease free survival (DFS) at 18 months
Time Frame:18 months
Safety Issue:
Description:Number of months from the date of first treatment until disease recurrence at 18 months. Estimation based on the Kaplan-Meier curve.
Measure:Disease free survival (DFS) at 3 years
Time Frame:3 years
Safety Issue:
Description:Number of months from the date of first treatment until disease recurrence at 3 years. Estimation based on the Kaplan-Meier curve.
Measure:Disease free survival (DFS) at 5 years
Time Frame:5 years
Safety Issue:
Description:Number of months from the date of first treatment until disease recurrence at 5 years. Estimation based on the Kaplan-Meier curve.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • Relatlimab
  • Nivolumab
  • Immunotherapy
  • Anti PD-1
  • Anti - LAG-3
  • Resectable hepatocellular Cancer
  • Potentially resectable hepatocellular Cancer
  • Hepatocellular Cancer (HCC)

Last Updated

December 8, 2020