Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04658147
Recruitment Status : Not yet recruiting
First Posted : December 8, 2020
Last Update Posted : February 11, 2021
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Nivolumab Drug: Relatlimab Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Feasibility and Efficacy of Perioperative Nivolumab With or Without Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma (HCC)
Estimated Study Start Date : April 2021
Estimated Primary Completion Date : April 2025
Estimated Study Completion Date : April 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Arm A - Nivolumab
Participants receive Nivolumab only.
Drug: Nivolumab
Nivolumab 480mg will be administered as a 30 minute IV infusion (-/+15min) at cycle 1 day 1 and at cycle 2 day 1 (28 days) then every month for up to 12 months. Intravenous administration of Nivolumab (480 mg) will occur on Cycle 1 and 2 of the study then every 28 days up to a year. Nivolumab will be administered on Day 1 of each cycle for 10 doses/ months (whichever occurs first) for adjuvant.
Other Names:
  • OPDIVO™
  • BMS 936558
  • MDX1106
  • ONO-4538

Experimental: Arm B - Nivolumab and Relatlimab
Participants receive Nivolumab and Relatlimab.
Drug: Nivolumab
Nivolumab 480mg will be administered as a 30 minute IV infusion (-/+15min) at cycle 1 day 1 and at cycle 2 day 1 (28 days) then every month for up to 12 months. Intravenous administration of Nivolumab (480 mg) will occur on Cycle 1 and 2 of the study then every 28 days up to a year. Nivolumab will be administered on Day 1 of each cycle for 10 doses/ months (whichever occurs first) for adjuvant.
Other Names:
  • OPDIVO™
  • BMS 936558
  • MDX1106
  • ONO-4538

Drug: Relatlimab
Patients will receive 960 mg Relatlimab intravenously (-/+15min) on cycle 1 day 1 and at cycle 2 day 1 (every 28 days) for up to 1 year co-administered with Nivolumab.
Other Names:
  • BMS-986016
  • BMS-986016-01
  • Anti-LAG-3




Primary Outcome Measures :
  1. Number of patients who complete pre-op treatment and proceed to surgery [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Number of participants experiencing study drug-related toxicities [ Time Frame: 4 years ]
    Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.

  2. Percentage of participants who obtain R0 resection [ Time Frame: 8 weeks ]
  3. Percentage of evaluable patients who obtain a pathologic complete response (pCR) or major pathologic response (MPR) [ Time Frame: 8 weeks ]
  4. Objective response rate (ORR) at 8 weeks [ Time Frame: 8 weeks ]
    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.

  5. Overall survival (OS) at 12 months [ Time Frame: 12 months ]
    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.

  6. Overall survival (OS) at 18 months [ Time Frame: 18 months ]
    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.

  7. Overall survival (OS) at 3 years [ Time Frame: 3 years ]
    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.

  8. Overall survival (OS) at 5 years [ Time Frame: 5 years ]
    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.

  9. Disease free survival (DFS) at 12 months [ Time Frame: 12 months ]
    Number of months from the date of first treatment until disease recurrence at 12 months. Estimation based on the Kaplan-Meier curve.

  10. Disease free survival (DFS) at 18 months [ Time Frame: 18 months ]
    Number of months from the date of first treatment until disease recurrence at 18 months. Estimation based on the Kaplan-Meier curve.

  11. Disease free survival (DFS) at 3 years [ Time Frame: 3 years ]
    Number of months from the date of first treatment until disease recurrence at 3 years. Estimation based on the Kaplan-Meier curve.

  12. Disease free survival (DFS) at 5 years [ Time Frame: 5 years ]
    Number of months from the date of first treatment until disease recurrence at 5 years. Estimation based on the Kaplan-Meier curve.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT04658147


Contacts
Layout table for location contacts
Contact: Bradley Wilt, RN 410-614-1816 bwilt1@jhmi.edu
Contact: Jane Zorzi, RN 410-955-1107 jzorzi1@jhmi.edu

Locations
Layout table for location information
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
Contact: Bradley Wilt, RN    410-614-1816    bwilt1@jhmi.edu   
Contact: Jane Zorzi, RN    410-955-1107    jzorzi1@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Bristol-Myers Squibb
Investigators
Layout table for investigator information
Principal Investigator: Mark Yarchoan, MD SKCCC Johns Hopkins Medical Institution
Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT04658147    
Other Study ID Numbers: J20121
IRB00246739 ( Other Identifier: Johns Hopkins Medical Internal Review Board )
First Posted: December 8, 2020    Key Record Dates
Last Update Posted: February 11, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Relatlimab
Nivolumab
Immunotherapy
Anti PD-1
Anti - LAG-3
Resectable hepatocellular Cancer
Potentially resectable hepatocellular Cancer
Hepatocellular Cancer (HCC)
Additional relevant MeSH terms:
Layout table for MeSH terms
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
Antineoplastic Agents, Immunological
Antineoplastic Agents