Perioperative Retlirafusp Alfa（Anti-PD-L1/TGF-β Bifunctional Fusion Protein） Plus Famitinib and GEMOX-Based Hepatic Arterial Infusion Chemotherapy for Locally Advanced Intrahepatic Cholangiocarcinoma: A Multicenter, Single-Arm, Exploratory Phase II Trial: H-FROG Feasibility Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Event-free survival (EFS)
研究概览
简要总结
This is a multicenter, single-arm, exploratory clinical study for adults with locally advanced intrahepatic cholangiocarcinoma (ICC) that may be technically resectable but is difficult to remove directly by surgery. The study will evaluate whether perioperative treatment with Retlirafusp alfa, famitinib malate, and hepatic arterial infusion chemotherapy using gemcitabine and oxaliplatin (HAIC-GEMOX) can help control the tumor before surgery and support further treatment after surgery.
Participants who meet the study requirements will receive neoadjuvant treatment before surgery. After surgery, participants will receive adjuvant treatment with Retlirafusp alfa combined with capecitabine or S-1. The study treatment and follow-up will continue until disease progression, unacceptable side effects, death, withdrawal of consent, or other protocol-defined stopping criteria.
The main purpose of the study is to evaluate event-free survival. The study will also monitor tumor response, surgery-related outcomes, survival, and safety. Participants will have regular safety visits, blood tests, imaging examinations, and follow-up visits during and after treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria:
- •Voluntarily agree to participate in the study and sign the informed consent form.
- •Age 18 to 75 years at the time of signing informed consent, male or female.
- •Histologically and/or cytologically confirmed intrahepatic cholangiocarcinoma.
- •ECOG performance status of 0 to
- •No prior systemic therapy or tumor-related surgery, except biliary drainage.
- •No extrahepatic metastasis.
- •Considered technically resectable by an experienced hepatobiliary surgeon.
- •At least one measurable lesion according to RECIST 1.
- •Adequate organ and bone marrow function, as defined by the protocol.
- •Women of childbearing potential must have a negative serum pregnancy test within 7 days before treatment and agree to use effective contraception during the study and for 1 year after the last study treatment. Male participants with partners of childbearing potential must also agree to use effective contraception during the study and for 1 year after the last study treatment.
- •Life expectancy of at least 12 weeks.
排除标准
- •Participants meeting any of the following criteria will be excluded:
- •Pathological diagnosis of hepatocellular carcinoma, mixed liver cancer, or other non-cholangiocarcinoma malignant tumor components.
- •Prior systemic therapy or other tumor-related treatment, except biliary drainage.
- •Diagnosis of any other malignancy within 5 years before the first study treatment, except cured localized tumors such as cervical carcinoma in situ, basal cell carcinoma of the skin, or low-grade prostate cancer.
- •Known uncontrolled pulmonary fibrosis, interstitial lung disease, or acute lung disease.
- •Participation in another clinical trial of an investigational drug or device within 4 weeks before the first study treatment.
- •Active hepatitis B or hepatitis C infection.
- •Active autoimmune disease requiring systemic treatment within 2 years before the first
研究组 & 干预措施
Combined treatment group
Participants in this single arm will receive perioperative treatment with rilvegostomig alpha, famitinib malate, and HAIC-GEMOX before surgery, followed by postoperative adjuvant therapy with rilvegostomig alpha plus capecitabine or S-1 when applicable.
干预措施: Rilvegostomig Alpha (Drug)
Combined treatment group
Participants in this single arm will receive perioperative treatment with rilvegostomig alpha, famitinib malate, and HAIC-GEMOX before surgery, followed by postoperative adjuvant therapy with rilvegostomig alpha plus capecitabine or S-1 when applicable.
干预措施: hepatic arterial infusion chemotherapy (HAIC) (Procedure)
Combined treatment group
Participants in this single arm will receive perioperative treatment with rilvegostomig alpha, famitinib malate, and HAIC-GEMOX before surgery, followed by postoperative adjuvant therapy with rilvegostomig alpha plus capecitabine or S-1 when applicable.
干预措施: Gemcitabine & oxaliplatin (Drug)
Combined treatment group
Participants in this single arm will receive perioperative treatment with rilvegostomig alpha, famitinib malate, and HAIC-GEMOX before surgery, followed by postoperative adjuvant therapy with rilvegostomig alpha plus capecitabine or S-1 when applicable.
干预措施: Famitinib malate (Drug)
Combined treatment group
Participants in this single arm will receive perioperative treatment with rilvegostomig alpha, famitinib malate, and HAIC-GEMOX before surgery, followed by postoperative adjuvant therapy with rilvegostomig alpha plus capecitabine or S-1 when applicable.
干预措施: Capecitabine (Drug)
Combined treatment group
Participants in this single arm will receive perioperative treatment with rilvegostomig alpha, famitinib malate, and HAIC-GEMOX before surgery, followed by postoperative adjuvant therapy with rilvegostomig alpha plus capecitabine or S-1 when applicable.
干预措施: S-1 (Drug)
结局指标
主要结局
Event-free survival (EFS)
时间窗: From the start of treatment until the first EFS event, assessed up to 36 months.
EFS is defined as the time from the start of treatment to the first occurrence of any event, including disease progression that precludes surgery, local or distant recurrence, or death from any cause.
次要结局
- Pathological complete response rate(At the time of surgical pathological assessment, assessed up to 36 months.)
- Major pathological response rate(At the time of surgical pathological assessment, assessed up to 36 months.)
- R0 resection rate(At the time of surgery, assessed up to 36 months.)
- Disease-free survival(From the date of surgery until recurrence or death, assessed up to 36 months.)
- Overall survival(From the start of neoadjuvant treatment until death or last follow-up, assessed up to 36 months.)
- Incidence and severity of adverse events(From the start of treatment through the safety follow-up period, assessed up to 36 months.)