Nivolumab Plus Ipilimumab as Neoadjuvant Therapy for Hepatocellular Carcinoma (HCC)

NCT03510871 | Completed Phase 2 DMC

• 1 other identifier: T2217
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 8

Brief Summary

Objectives:

1. 1.To evaluate the efficacy, in terms of tumor shrinkage, objective response rate, and down-stage rate, of nivolumab + ipilimumab as neoadjuvant therapy for patients with HCC;
2. 2.To evaluate the safety profile in patients with HCC who receive neoadjuvant nivolumab + ipilimumab treatment;
3. 3.To collect HCC tumor tissue and peripheral blood samples from the patients for a comprehensive biomarker evaluation for nivolumab + ipilimumab immunotherapy.

Conditions

Hepatocellular Carcinoma (HCC)

Keywords

neoadjuvant therapy; immunotherapy

Outcome Measures

Primary Outcomes (1)

• the percentage of subjects with tumor shrinkage after study drug treatment

  \> 10% of decrease of the sum of the target lesions according to RECIST 1.1

  4 years

Study Arms (1)

nivolumab plus ipilimumab

EXPERIMENTAL

nivolumab plus ipilimumab

Drug: nivolumab, ipilimumab

Interventions

nivolumab, ipilimumab DRUG

All enrolled subjects will receive nivolumab 3 mg/kg plus ipilimumab 1 mg/kg intravenously on day 1 of each cycle (every 3 weeks). Tumor assessment will be done after 6 weeks (2 cycles) and 12 weeks (4 cycles).

Also known as: nivolumab plus ipilimumab

nivolumab plus ipilimumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological diagnosis of HCC with potential for curative surgical resection fulfilling one of the following criteria:
• (A)Tumor(s) with macrovascular invasion. (B)Tumors with one of the following features: (B1)multiple tumors and bilateral lobes involvement, none more than 5 cm (B2)tumor number \> 3, none more than 5 cm (B3)multiple tumors none more than 5 cm, with significant portal hypertension (splenomegaly, esophageal varices or platelet \< 100,000/μL) (B4)solitary tumor \> 5 cm, with significant portal hypertension (splenomegaly, esophageal varices or platelet \< 100,000/μL) (B5)Other conditions that are considered high-risk for recurrence after surgery, e.g., direct diaphragmic invasion suspected by imaging。
• No evidence of extra-hepatic metastases.
• At least one measurable tumor, according to RECIST version 1.1, that has not been treated with any local procedure.
• Prior percutaneous ethanol injection, radiofrequency ablation, transarterial embolization, or cryotherapy are allowed if aforementioned local therapy is given at least 4 weeks prior to enrollment and progressive or recurrent disease is documented.
• Age \>= 20 years old.
• ECOG performance status 0 or 1.
• Child-Pugh class A liver function.
• WBC \>=2,000/uL (stable, off any growth factor within 4 weeks of study drug administration) ; Platelet\>= 60,000/uL.
• Liver transaminases (ALT and AST) \<= 5 times upper limit of normal values (ULN); total bilirubin \<=1.5 times ULN; serum creatinine\<=1.5 times ULN; creatinine clearance \> 50 mL/min (calculated by Cockcroft-Gault formula)
• Subjects with chronic hepatitis B virus infection (HBV surface antigen (HBsAg) positive) must start antiviral therapy with nucleoside analogs (e.g., entecavir or tenofovir, according to current practice guidelines) before start of study drug treatment.
• Signed informed consent.

You may not qualify if:

• Receiving concurrent anti-cancer therapy for HCC, which includes local therapy, systemic therapy, or other experimental therapy.
• Local treatment including radiotherapy (except palliative radiotherapy), percutaneous ethanol injection, radiofrequency ablation, or transarterial embolization administered within 4 weeks prior to enrollment.
• Major surgical procedure within 2 weeks or minor surgical procedure within 1 week prior to enrollment.
• History of esophageal/gastric varices or active peptic ulcers that are considered to have high risk of bleeding.
• History of upper gastrointestinal bleeding within 1 year.
• Known human immunodeficiency virus (HIV) infection.
• Major systemic diseases that the investigator considers inappropriate for participation.
• History of other malignancies except those treated with curative intent for skin cancer (other than melanoma), in situ breast or in situ cervical cancer, or those treated with curative intent for any other cancer with no evidence of disease for 2 years.
• Any active autoimmune disease or history of known autoimmune disease except for vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
• Requirement of systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Prior organ allograft or allogeneic bone marrow transplantation.
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation and in the judgment of the investigator would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• National Health Research Institutes, Taiwan: lead
• National Taiwan University Hospital: collaborator
• Taipei Veterans General Hospital, Taiwan: collaborator
• National Cheng-Kung University Hospital: collaborator
• China Medical University Hospital: collaborator
• Chang Gung Memorial Hospital: collaborator
• Mackay Memorial Hospital: collaborator
• Tri-Service General Hospital: collaborator

Study Sites (8)

Chang-Gung Memorial Hospital, Kaohsiung

Kaohsiung City, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

National Cheng-Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Mackay Memorial Hospital

Taipei, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Tri-Service General Hospital

Taipei, Taiwan

Location

Chang-Gung Memorial Hospital, Linkou

Taoyuan District, Taiwan

Location

Related Publications (1)

• Lin YJ, Ou DL, Su YY, Hsu CL, Hsiao CF, Ko BS, Chen SC, Wang HW, Wang JH, Wu YM, Jeng YM, Lee WC, Chou SC, Chen TW, Chiu CF, Lin JS, Hsieh CH, Lee CC, Shan YS, Cheng AL, Chen LT, Hsu C. Nivolumab plus ipilimumab for potentially resectable hepatocellular carcinoma: Long-term efficacy and biomarker exploration. J Hepatol. 2026 Feb;84(2):316-328. doi: 10.1016/j.jhep.2025.08.035. Epub 2025 Sep 17.

  PMID: 40972843 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Tsang-Wu Liu, MD, PhD

  Taiwan Cooperative Oncology Group, NHRI

  STUDY CHAIR

• Chiun Hsu, MD, PhD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: April 27, 2018
• Study Start: February 12, 2019
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: July 8, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

TW (8)