Feasibility and Efficacy of Perioperative Nivolumab With or Without Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma (HCC)
- Registration Number
- NCT04658147
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 20
• 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A - Nivolumab Nivolumab Participants receive Nivolumab only. Arm B - Nivolumab and Relatlimab Nivolumab Participants receive Nivolumab and Relatlimab. Arm B - Nivolumab and Relatlimab Relatlimab Participants receive Nivolumab and Relatlimab.
- Primary Outcome Measures
Name Time Method Number of patients who complete pre-op treatment and proceed to surgery 4 years
- Secondary Outcome Measures
Name Time Method Percentage of participants who obtain R0 resection 8 weeks Overall survival (OS) at 12 months 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.
Overall survival (OS) at 18 months 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.
Disease free survival (DFS) at 12 months 12 months Number of months from the date of first treatment until disease recurrence at 12 months. Estimation based on the Kaplan-Meier curve.
Disease free survival (DFS) at 3 years 3 years Number of months from the date of first treatment until disease recurrence at 3 years. Estimation based on the Kaplan-Meier curve.
Number of participants experiencing study drug-related toxicities 4 years Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.
Percentage of evaluable patients who obtain a pathologic complete response (pCR) or major pathologic response (MPR) 8 weeks Objective response rate (ORR) at 8 weeks 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.
Overall survival (OS) at 3 years 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.
Overall survival (OS) at 5 years 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.
Disease free survival (DFS) at 18 months 18 months Number of months from the date of first treatment until disease recurrence at 18 months. Estimation based on the Kaplan-Meier curve.
Disease free survival (DFS) at 5 years 5 years Number of months from the date of first treatment until disease recurrence at 5 years. Estimation based on the Kaplan-Meier curve.
Trial Locations
- Locations (2)
The Ohio State University, Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States