A Prospective, Open-label, Single-arm, Phase 2 Study of Hepatic Arterial Infusion Chemotherapy Combined With Lenvatinib and Cadonilimab as Conversion Therapy for Initially Unresectable Hepatocellular Carcinoma
概览
- 阶段
- 2 期
- 干预措施
- Hepatic arterial infusion chemotherapy (HAIC-FOLFOX)
- 疾病 / 适应症
- Hepatocellular Carcinoma Non-resectable
- 发起方
- Tongji Hospital
- 入组人数
- 44
- 试验地点
- 2
- 主要终点
- Number of Patients Amendable to Curative Surgical Interventions
- 状态
- 进行中（未招募）
- 最后更新
- 8天前
概览
简要总结
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.
详细描述
Hepatocellular carcinoma is frequently diagnosed at an unresectable stage, and effective conversion strategies are needed to increase the chance of subsequent curative-intent treatment. This study is a prospective, open-label, single-arm, phase 2 trial evaluating HAIC-FOLFOX combined with lenvatinib and cadonilimab in participants with initially unresectable HCC. Eligible participants will receive HAIC-FOLFOX every 3 weeks, lenvatinib orally once daily, and cadonilimab intravenously every 3 weeks. Tumor response and resectability will be evaluated during treatment by a multidisciplinary team (MDT). Curative-intent treatment includes R0 resection, curative ablation, or liver transplantation. The primary endpoint is conversion rate, defined as the proportion of participants who are deemed amenable to curative-intent treatment by the MDT after study treatment. Secondary endpoints include the curative-intent intervention rate, objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), time to response (TTR), duration of response (DoR), safety, pathological complete response (pCR), major pathological response (MPR), and exploratory tissue and blood biomarkers. Participants will be followed for up to 2 years.
研究者
入排标准
入选标准
- •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
- •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):
排除标准
- •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.
研究组 & 干预措施
HAIC + lenvatinib + cadonilimab
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.
干预措施: Hepatic arterial infusion chemotherapy (HAIC-FOLFOX)
HAIC + lenvatinib + cadonilimab
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.
干预措施: Lenvatinib
HAIC + lenvatinib + cadonilimab
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.
干预措施: Cadonilimab
结局指标
主要结局
Number of Patients Amendable to Curative Surgical Interventions
时间窗: from the date of first treatment to the date of last treatment, an average of 3 years
Number of patients amendable to curative surgical interventions defined as number of patients receiving curative surgical resection, transplantation, or ablation after successful down-sizing of tumor(s) by intervention.
Conversion rate
时间窗: From the date of first treatment to confirmed MDT assessment of amenability to curative-intent treatment, assessed up to 2 years
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.
次要结局
- Time to progression (TTP)(from the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 3 years)
- Duration of response (DoR)(from the date of first documented evidence of CR or PR to first documented sign of PD or death from any cause according to mRECIST 1.1, assessed up to 3 years)
- Incidence of Study-Related Adverse Events(from the date of first treatment to 90 days after last treatment, around 3 years and 90 days)
- Pathological complete response (pCR)(from the date of first study treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 5 years)
- Overall survival (OS)(from the date of first treatment to the date of death from any cause, assessed up to 5 years)
- overall response rate (ORR) measured by mRECIST criteria(from the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 3 years)
- Progression-free survival (PFS)(from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 3 years)
- Time to intrahepatic tumor progression (TTITP)(from the date of first treatment to radiographically documented intrahepatic tumor progression according to mRECIST, assessed up to 3 years)
- Disease control rate (DCR)(from the date of first treatment to radiographically documented response according to mRECIST, assessed up to 3 years)
- Quality of Life (QoL) after treatment(assessed form the date of first followup to radiographically documented progression or or death from any cause, up to 3 years)
- 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)
- Overall survival (OS)(From the date of first treatment to the date of death from any cause, assessed up to 2 years)
- Progression-free survival (PFS) by mRECIST(From the date of first treatment to radiographically documented progression according to mRECIST or death from any cause, whichever occurs first, assessed up to 2 years)
- Time to progression (TTP) by mRECIST(From the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 2 years)
- Time to response (TTR) by mRECIST(From the date of first treatment to the date of first documented CR or PR according to mRECIST, assessed up to 2 years)
- Duration of response (DoR) by mRECIST(From the date of first documented CR or PR according to mRECIST to first documented progression or death from any cause, assessed up to 2 years)
- Incidence of treatment-related adverse events (TRAEs)(From the date of first treatment to 90 days after last study treatment, assessed up to 2 years and 90 days)
- Pathological complete response (pCR)(At the time of curative-intent resection or liver transplantation, assessed up to 2 years)
- Major pathological response (MPR)(At the time of curative-intent resection or liver transplantation, assessed up to 2 years)
- Exploratory tissue and blood biomarkers associated with treatment response(Baseline, at confirmed conversion success if applicable, at curative-intent surgery if applicable, and at disease progression, assessed up to 2 years)