HAIC, Lenvatinib, and Cadonilimab as Conversion Therapy for Initially Unresectable Hepatocellular Carcinoma

NCT06187961 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 2023-S039
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, phase 2 study evaluating hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and cadonilimab as conversion therapy for initially unresectable hepatocellular carcinoma (HCC). The primary objective is to assess the conversion rate, defined as the proportion of participants who are deemed amenable to curative-intent treatment by the multidisciplinary team (MDT), including R0 resection, curative ablation, or liver transplantation, after study treatment. Secondary objectives include curative-intent intervention rate, tumor response, survival outcomes, safety, pathological response, and exploratory tissue and blood biomarkers.

Conditions

Hepatocellular Carcinoma Non-resectable

Keywords

Cadonilimab; Lenvatinib; Downstaging conversion therapy; Hepatocellular Carcinoma; Hepatic Arterial Infusion Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Conversion rate

  Proportion of participants who are deemed amenable to curative-intent treatment by the multidisciplinary team (MDT), including R0 resection, curative ablation, or liver transplantation, after study treatment. Conversion success will be confirmed only when MDT-defined amenability to curative-intent treatment is maintained for at least 2 months, unless curative-intent treatment is actually performed earlier.

  From the date of first treatment to confirmed MDT assessment of amenability to curative-intent treatment, assessed up to 2 years

Secondary Outcomes (14)

• Curative-intent intervention rate

  From the date of first treatment to receipt of curative-intent treatment, assessed up to 2 years

• Overall response rate (ORR) by mRECIST

  Best overall response from the date of first treatment until radiographic disease progression, start of new anti-cancer therapy, death, withdrawal, or end of study, assessed up to 2 years

• Overall response rate (ORR) by RECIST 1.1

  Best overall response from the date of first treatment until radiographic disease progression, start of new anti-cancer therapy, death, withdrawal, or end of study, assessed up to 2 years

• Disease control rate (DCR) by mRECIST

  Best overall response from the date of first treatment until radiographic disease progression, start of new anti-cancer therapy, death, withdrawal, or end of study, assessed up to 2 years

• Disease control rate (DCR) by RECIST 1.1

  Best overall response from the date of first treatment until radiographic disease progression, start of new anti-cancer therapy, death, withdrawal, or end of study, assessed up to 2 years

Study Arms (1)

HAIC + lenvatinib + cadonilimab

EXPERIMENTAL

Participants with initially unresectable hepatocellular carcinoma who are evaluated as unsuitable for curative-intent treatment at baseline and receive combined HAIC-FOLFOX, lenvatinib, and cadonilimab as conversion therapy.

Procedure: Hepatic arterial infusion chemotherapy (HAIC-FOLFOX); Drug: Lenvatinib; Drug: Cadonilimab

Interventions

Hepatic arterial infusion chemotherapy (HAIC-FOLFOX) PROCEDURE

Administration of oxaliplatin, leucovorin, and fluorouracil via the tumor-feeding hepatic artery every 3 weeks.

Also known as: hepatic arterial infusion chemotherapy of FOLFOX

HAIC + lenvatinib + cadonilimab

Lenvatinib DRUG

Lenvatinib administered orally once daily at 8 mg for participants weighing ≤60 kg or 12 mg for participants weighing \>60 kg.

HAIC + lenvatinib + cadonilimab

Cadonilimab DRUG

Cadonilimab administered intravenously at 10 mg/kg every 3 weeks.

HAIC + lenvatinib + cadonilimab

Eligibility Criteria

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

You may qualify if:

• Hepatocellular carcinoma proven on biopsy or confirmed by radiological hallmarks according to the American Association for the Study of Liver Diseases (AASLD) or the European Association for the Study of the Liver (EASL) guidelines.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Not suitable for curative-intent treatment (including radical hepatic resection, liver transplantation, or curative ablation) after evaluation by the hepatobiliary tumor MDT expert group. Specifically, any of the following conditions are met:
• R0 resection is not feasible.
• In participants without cirrhosis, the volume of normal liver parenchyma is less than 30% of the total liver volume; or in participants with cirrhosis, the volume of normal liver parenchyma is less than 40% of the total liver volume; or ICG-R15 \>15%.
• BCLC stage B or C.
• No prior systemic anti-tumor treatment for hepatocellular carcinoma before the first dose.
• According to RECIST version 1.1, at least 1 measurable lesion, or a measurable lesion that has clearly progressed after local treatment.
• Participants with portal vein tumor thrombus (PVTT):
• Chen's group A and B, or Cheng's type I-III, can be enrolled.
• Cheng's type IV, defined as superior mesenteric vein tumor thrombus, cannot be enrolled.
• Participants with hepatic vein tumor thrombus:
• VV1 and VV2 can be enrolled.
• VV3, or Sakamoto type I (inferior vena cava tumor thrombus), can also be enrolled.

You may not qualify if:

• Histologically or cytologically confirmed fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, or mixed histology.
• History of hepatic encephalopathy or liver transplantation.
• Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage. Participants with only minimal radiologic effusion without symptoms may be enrolled.
• Acute or chronic active hepatitis B or C infection, with HBV DNA \>2000 IU/mL or 10\^4 copies/mL, HCV RNA \>10\^3 copies/mL, or co-positivity for HBsAg and anti-HCV antibody. Participants controlled to within these limits after antiviral therapy may be enrolled.
• Central nervous system metastases.
• History of esophageal or gastric variceal bleeding due to portal hypertension within 6 months before first dose, or high bleeding risk judged by the investigator.
• Any life-threatening bleeding event within 3 months before first dose.
• History of arterial or venous thromboembolic events within 6 months before first dose, including myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other serious thromboembolic events, except stabilized catheter-related thrombosis or superficial thrombosis.
• Continuous use of aspirin \>325 mg/day or other known platelet inhibitors for 10 days within 2 weeks before first dose.
• Uncontrolled hypertension despite optimal treatment, defined as systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg, or history of hypertensive crisis or hypertensive encephalopathy.
• Toxicities from previous treatment not recovered to grade 0 or 1 per NCI-CTCAE version 5.0, except alopecia or clinically insignificant asymptomatic laboratory abnormalities.
• Symptomatic congestive heart failure (NYHA class II-IV) or left ventricular ejection fraction \<50%.
• Symptomatic or poorly controlled arrhythmia, history of congenital long QT syndrome, or screening QTc \>500 ms by Fridericia formula.
• Severe bleeding tendency, coagulation disorder, or current thrombolytic therapy.
• Gastrointestinal perforation or fistula, intestinal obstruction, extensive bowel resection with chronic diarrhea, Crohn's disease, ulcerative colitis, or chronic diarrhea within 6 months before first dose.

Sponsors & Collaborators

• Tongji Hospital: lead
• Akesobio: collaborator

Study Sites (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib

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

Study Officials

• Ze-yang Ding, M.D.

  Tongji Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: December 8, 2023
• First Posted: January 3, 2024
• Study Start: December 7, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

CN (1)