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Hepatocellular Carcinoma (HCC)Phase 2CA209-1594NCT07919717

NIVO+IPI Neoadjuvant Therapy for Recurrent Resectable HCC

A Phase 2 study testing Nivolumab, Ipilimumab and Repeat Hepatectomy in people with Hepatocellular Carcinoma (HCC) and Recurrent Hepatocellular Cancer, run by Shanghai Zhongshan Hospital at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This study will evaluate nivolumab and ipilimumab, two immunotherapy medicines, given before repeat liver surgery in adults whose liver cancer (hepatocellular carcinoma) has returned within the liver after previous surgery. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Nivolumab, Ipilimumab and Repeat Hepatectomy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteChina
Study dates
1 Nov 2026to 12 Apr 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The subject or their legally authorized representative must sign a written informed consent form (ICF) approved by the IRB/IEC, with the date indicated, prior to undergoing any study-related procedures.
  • Subjects must be willing and able to comply with the scheduled visits, treatment regimen, laboratory assessments, and other study requirements.
  • Male and female subjects aged >= 18 and <= 75 years.
  • Expected life expectancy of >= 3 months.
  • Subjects must have histologically, cytologically, or clinically confirmed HCC.
  • Subjects should, as much as possible, provide tumor tissue specimens from the initial surgical resection of HCC (1 formalin-fixed paraffin-embedded [FFPE] tissue block or 20 unstained tumor tissue slides) during the screening period.
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  • Subjects must have intrahepatic recurrence confirmed by imaging (contrast-enhanced CT or MRI) occurring 3 months to 2 years after initial liver resection.
  • Subjects must be assessed by the investigator as eligible for repeat hepatic resection, in accordance with the Chinese Expert Consensus on Prevention and Treatment of Postoperative Recurrence of Hepatocellular Carcinoma (2020 edition):
  • Subjects in generally good condition.
  • Liver function Child-Pugh class A, with none or only mild portal hypertension.
  • No severe underlying diseases of major organs such as heart, lung, or kidney.
  • Lesion(s) are either solitary or multiple (<= 3) with the maximum diameter of a single lesion <= 3 cm, and technically resectable; for multiple lesions, enrollment is allowed only after investigator assessment of the remaining liver volume and surgical safety margins.
  • Expected residual liver volume after repeat hepatectomy sufficient to maintain adequate liver function.
  • No major vascular invasion or extrahepatic distant metastasis.
  • Subjects must have at least one previously untreated lesion that is measurable according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  • The lesion must be accurately measured in at least one dimension using contrast-enhanced spiral computed tomography (CT) or contrast-enhanced dynamic magnetic resonance imaging (MRI), with a result >= 10 mm. Note: for malignant lymph nodes, the short axis must be >= 15 mm.
  • The lesion must not have been previously treated with surgery, radiotherapy, and/or local regional therapy (e.g., RFA, PEI or PAI, cryoablation, HIFU, TACE, TAE, etc.).
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0.
  • Subjects must not have received prior systemic immune checkpoint inhibitor therapy.
  • Subjects must have adequate organ and bone marrow function. Screening laboratory values must meet the following criteria and must be obtained within 7 days prior to enrollment (administration of any blood products, growth factors, albumin, or other corrective treatments is not permitted within 14 days prior to obtaining the laboratory assessments):
  • Adequate hematologic function:
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelet count (PLT) >= 75 x 10^9/L
  • Hemoglobin (HGB) >= 9.0 g/dL
  • Adequate hepatic function:
  • Serum total bilirubin (TBIL) <= 2 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 5 x ULN
  • Serum albumin >= 28 g/L
  • Alkaline phosphatase (ALP) <= 5 x ULN
  • In the Child-Pugh classification, only one of the 2 parameters, albumin or bilirubin, may be scored as 2 points.
  • Adequate renal function:
  • Serum creatinine (Cr) <= 1.5 x ULN or creatinine clearance (CCr) >= 50 mL/min (calculated using the Cockcroft-Gault formula)
  • Urinalysis showing protein < 2+
  • For subjects with baseline urinalysis showing protein >= 2+, a 24-hour urine collection must be performed, with 24-hour urine protein < 1g
  • Adequate coagulation function:
  • International Normalized Ratio (INR) and activated partial thromboplastin time (APTT) <= 1.5 x ULN
  • Subjects with HBV or HCV infection must meet the following criteria:
  • HBV infection: If HBsAg positive, HBV-DNA must be measured, and HBV-DNA must be < 2000 IU/mL or < 10^4 copies/mL. Subjects must have received at least 1 week of anti-HBV therapy prior to enrollment and be willing to continue antiviral therapy throughout the study.
  • HCV infection: HCV-RNA positive subjects (RNA < 10^3 copies/mL) must receive antiviral therapy according to treatment guidelines.
  • Women of childbearing potential (WOCBP) must have a serum pregnancy test within 7 days prior to enrollment, with a negative result (minimum sensitivity 25 IU/L or equivalent HCG units).
  • Female subjects must not be breastfeeding.
  • Female subjects of reproductive potential and their partners must agree to use effective contraception during the study and for at least 6 months after the last dose. WOCBP must also agree not to donate oocytes during this period.

Who cannot join

  • Histologically confirmed fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma-HCC.
  • Prior liver transplantation.
  • Presence of extrahepatic metastases or unresectable lesions confirmed by imaging within 1 month prior to enrollment.
  • Recurrence within less than 3 months after surgery.
  • Lesions assessed as unresectable.
  • Prior systemic antitumor therapy for recurrent HCC, including but not limited to immunotherapy (PD-1, PD-L1, CTLA-4 antibodies, or bispecific/combination antibodies).
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  • Prior local therapy after recurrence, including transarterial chemoembolization (TACE), ablation (radiofrequency ablation, microwave ablation, cryoablation, etc.), or radiotherapy.
  • Active co-infection with hepatitis B and hepatitis C or hepatitis B and hepatitis D that is not effectively controlled.
  • Known human immunodeficiency virus (HIV)-positive history or known AIDS history, or currently receiving systemic corticosteroid therapy. Note: HIV testing must be performed at a locally authorized institution.
  • Active bacterial, fungal, or viral infection requiring systemic therapy within 1 week prior to enrollment.
  • History of hepatic encephalopathy (>= Grade 2) within 12 months prior to enrollment.
  • Clinically significant ascites, defined as:
  • Ascites previously requiring treatment and ongoing prophylaxis, or
  • Ascites currently requiring treatment.
  • Presence of portal hypertension with a history of bleeding from esophageal or gastric varices within 6 months prior to enrollment.
  • Uncontrolled cardiac clinical symptoms or diseases, including but not limited to:
  • Uncontrolled hypertension despite optimal therapy, defined as systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg.
  • History of congestive heart failure greater than New York Heart Association (NYHA) class II.
  • Active coronary artery disease, unstable or newly diagnosed angina, or myocardial infarction within 6 months prior to screening.
  • Arrhythmias requiring antiarrhythmic therapy other than beta-blockers or digoxin at screening.
  • Cardiac valvular disease graded > Grade 2 according to CTCAE.
  • QTc interval (Fridericia formula) > 480 ms on 2 consecutive ECGs.
  • Symptomatic or potentially interfering interstitial lung disease that may affect the detection or management of drug-related pulmonary toxicity.
  • History of gastrointestinal or non-gastrointestinal fistula or gastrointestinal perforation.
  • History of non-healing wounds or skin ulcers within 3 months prior to enrollment.
  • History of thrombotic or embolic events (excluding HCC tumor thrombus) within 6 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks) or pulmonary embolism.
  • History of any CTCAE Grade >= 3 hemorrhagic events within 8 weeks prior to enrollment, or currently receiving thrombolytic therapy.
  • Systemic treatment with corticosteroids (> 10 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days prior to study drug administration.
  • Immunological contraindications or concurrent severe autoimmune diseases where the investigator considers immune checkpoint inhibitor therapy to carry excessive risk, including but not limited to:
  • Active severe autoimmune diseases (e.g., systemic lupus erythematosus, Sjogren's syndrome, myasthenia gravis, ulcerative colitis, Crohn's disease, refractory psoriasis, etc.) requiring medium- to high-dose immunosuppressive therapy for maintenance.
  • Confirmed severe combined immunodeficiency, acquired immunodeficiency syndrome (AIDS), or immunodeficiency states such as critically low CD4+ T-cell counts.
  • Recent (e.g., <= 14 days) or ongoing use of high-dose systemic corticosteroids (> 10 mg/day prednisone equivalent) or other drugs affecting immune function (short-term use for irAE management or perioperative period is not included).
  • Requirement for ongoing immunosuppressive therapy due to organ transplantation.
  • Investigator's assessment based on medical history or current condition indicates other high-risk immunologic abnormalities that make the subject unsuitable for immune checkpoint inhibitor therapy.
  • Known hypersensitivity to Nivolumab, Ipilimumab, any of their excipients, or history of severe hypersensitivity reactions to other monoclonal antibodies.
  • Presence of concomitant malignancy requiring treatment (at screening) or history of active prior malignancy within 2 years prior to enrollment. Note: Subjects with a history of prior malignancy are eligible if treatment was completed >= 2 years ago and there is no evidence of disease. Additionally, subjects with a history of prior early-stage basal/squamous cell skin cancer or non-invasive/in situ carcinoma are eligible if they received targeted therapy at any time.
  • Any serious or uncontrolled medical condition that, in the investigator's opinion, may increase the risk of participation, compromise the subject's ability to receive study treatment, or interfere with the interpretation of study results.
  • History of major surgical procedures, open biopsies, or significant trauma within 4 weeks prior to enrollment, or minor surgical procedures (e.g., core needle biopsy) within 1 week prior to enrollment.
  • Subjects with a history of life-threatening toxicities related to prior systemic anticancer therapy, except for those unlikely to recur after standard-of-care management.
  • Pregnant or breastfeeding women of childbearing potential (WOCBP).

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Zhi-qiang Hu, MD contact

+8618317087726

hu.zhiqiang@zs-hospital.sh.cn

Guo-ming Shi, MD contact

+8613916969578

shi.guoming@zs-hospital.sh.cn

China1 site

  • Zhongshan Hospital, Fudan University

    Shanghai, Shanghai Municipality, 464200

    Zhi-qiang Hu, MD, +8618317087726, hu.zhiqiang@zs-hospital.sh.cn

    Guo-ming Shi, MD, shi.guoming@zs-hospital.sh.cn

Other trials in China

About this study

Official title: A Multicenter, Single-Arm, Phase II Open-Label Clinical Study of Nivolumab Combined With Ipilimumab in Patients With Resectable Hepatocellular Carcinoma (HCC) Experiencing Early Postoperative Recurrence

This study will evaluate nivolumab and ipilimumab, two immunotherapy medicines, given before repeat liver surgery in adults whose liver cancer (hepatocellular carcinoma) has returned within the liver after previous surgery.

Participants are planned to receive both medicines by intravenous infusion once every 3 weeks for 2 cycles, followed by surgery if they remain suitable. Researchers will examine the removed tumor tissue to assess treatment response. Treatment side effects and surgical outcomes will also be evaluated.

Read the detailed description

This multicenter, single-arm, open-label, Phase II study will evaluate the efficacy, safety, and surgical feasibility of neoadjuvant nivolumab plus ipilimumab in recurrent hepatocellular carcinoma. The study plans to enroll up to 35 adults with intrahepatic recurrence occurring 3 months to 2 years after initial liver resection who are considered suitable for repeat hepatectomy.

Participants are scheduled to receive nivolumab 3 mg/kg by intravenous infusion, followed by ipilimumab 1 mg/kg by intravenous infusion on the same day. Both medicines will be administered on Day 1 of each 3-week cycle for a total of 2 cycles.

Imaging and surgical reassessment are scheduled for Day 43 (+/-3 days) after the first dose. Repeat hepatectomy is planned between Day 43 and Day 90 after the first dose for participants who remain suitable for surgery.

The primary endpoint is the major pathological response rate. Major pathological response is defined as 50% or less residual viable tumor cells in the tumor bed and will be assessed by central pathological review of the resected specimen. Other assessments include pathological complete response, tumor response on imaging, recurrence-free survival, overall survival, treatment safety, and surgical outcomes.

Being tested
Nivolumab, Ipilimumab, Repeat Hepatectomy
Keywords
Hepatocellular carcinoma, Neoadjuvant therapy, Nivolumab, Ipilimumab, Immunotherapy, Liver resection, Major pathological response, Early postoperative recurrence
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabBiological

    Also called Opdivo®, NIVO

    Nivolumab 3 mg/kg is administered by intravenous infusion of each 3-week cycle (Q3W), for a total of 2 cycles. It is administered before ipilimumab on the same day.

  • IpilimumabBiological

    Also called Yervoy®, IPI

    Ipilimumab 1 mg/kg is administered by intravenous infusion of each 3-week cycle (Q3W), for a total of 2 cycles. It is administered after nivolumab on the same day.

  • Repeat HepatectomyProcedure or surgery

    Repeat Hepatectomy

Study groups in NCT07919717
Study groupRoleWhat they receive
Neoadjuvant Nivolumab Plus Ipilimumab Followed by Repeat HepatectomyExperimentalParticipants are scheduled to receive nivolumab 3 mg/kg followed by ipilimumab 1 mg/kg, each administered by intravenous infusion on Day 1 of each 3-week cycle, for 2 cycles. Radiographic and surgical re-evaluation will be performed on Day 43 (+/-3 days) after the first dose. Participants who remain eligible for surgery will undergo repeat hepatectomy, planned for Day 43 through Day 90 after the first dose.
Receives: Biological: Nivolumab; Biological: Ipilimumab; Procedure: Repeat Hepatectomy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Major Pathological Response (MPR) Rate

    Percentage of participants who achieve major pathological response, defined as 50% or less residual viable tumor cells in the tumor bed, as determined by pathological assessment of the repeat hepatectomy specimen.

    Measured: Day 43 through Day 90 after the first dose

Secondary outcomes (11)

  1. Pathological Complete Response (pCR) Rate

    Percentage of participants who achieve pathological complete response, defined as no residual viable tumor cells in the tumor bed, as determined by pathological assessment of the repeat hepatectomy specimen.

    Measured: Day 43 through Day 90 after the first dose

  2. Preoperative Objective Response Rate (ORR) According to RECIST Version 1.1

    Percentage of participants with a best overall response of complete response or partial response before repeat hepatectomy, as assessed by the investigator according to RECIST version 1.1.

    Measured: From baseline through the preoperative tumor assessment on Day 43 (±3 days) after the first dose

  3. Preoperative Objective Response Rate (ORR) According to Modified RECIST (mRECIST)

    Percentage of participants with a best overall response of complete response or partial response before repeat hepatectomy, based on assessment of viable hepatocellular carcinoma according to mRECIST.

    Measured: From baseline through the preoperative tumor assessment on Day 43 (±3 days) after the first dose

  4. Recurrence-Free Survival (RFS)

    Time from completion of repeat hepatectomy to the first documented recurrence confirmed by imaging or histology, or death from any cause, whichever occurs first.

    Measured: From repeat hepatectomy until recurrence or death, assessed every 12 weeks (±7 days) for up to 2 years after surgery

  5. Overall Survival (OS)

    Time from study entry to death from any cause.

    Measured: From study entry until death from any cause, assessed every 3 months (±7 days) for up to 5 years

  6. Incidence of Adverse Events and Serious Adverse Events

    Percentage of treated participants who experience adverse events, serious adverse events, immune-mediated adverse events, treatment-related adverse events, deaths, or clinically significant laboratory abnormalities. Event severity will be graded according to NCI CTCAE version 6.0.

    Measured: From the first dose through 30 days (±7 days) after the later of completion of neoadjuvant therapy or repeat hepatectomy

  7. Repeat Hepatectomy Rate

    Percentage of enrolled participants who undergo repeat hepatectomy after neoadjuvant treatment.

    Measured: From Day 43 after the first dose through completion or cancellation of the planned repeat hepatectomy

  8. R0 Resection Rate

    Percentage of participants undergoing repeat hepatectomy who achieve microscopically margin-negative resection.

    Measured: Day 43 through Day 90 after the first dose

  9. Surgery Delay Rate

    Percentage of participants whose planned repeat hepatectomy is delayed beyond Day 90 after the first dose.

    Measured: Day 90 after the first dose

  10. Surgery Cancellation Rate

    Percentage of participants whose planned repeat hepatectomy is canceled after neoadjuvant treatment.

    Measured: From completion of neoadjuvant treatment through Day 90 after the first dose

  11. Incidence of Surgery-Related Adverse Events and Serious Adverse Events

    Percentage of participants who experience surgery-related adverse events, serious adverse events, or postoperative complications following repeat hepatectomy.

    Measured: From repeat hepatectomy through 30 days (±7 days) after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2026
  2. Study start1 Nov 2026 (estimated)
  3. Primary completion12 May 2027 (estimated)
  4. Study completion12 Apr 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a single-arm study. Participants are scheduled to receive nivolumab 3 mg/kg followed by ipilimumab 1 mg/kg by intravenous infusion on Day 1 of each 3-week cycle for 2 cycles. Radiographic and surgical re-evaluation is scheduled for Day 43 (+/-3 days) after the first dose. Repeat hepatectomy is planned for Day 43 through Day 90 after the first dose for participants who remain eligible for surgery.
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07919717
Sponsor's protocol ID
CA209-1594
Acronym
CA209-1594
Status last verified
Oct 2026
First submitted
7 Oct 2026
Last updated
5 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Ipilimumab and Repeat Hepatectomy in people with Hepatocellular Carcinoma (HCC) and Recurrent Hepatocellular Cancer, run by Shanghai Zhongshan Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 42 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Zhi-qiang Hu, MD (+8618317087726, hu.zhiqiang@zs-hospital.sh.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major Pathological Response (MPR) Rate (time frame: Day 43 through Day 90 after the first dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07919717.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.

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