Gemox Combined With Anlotinib and Sintilimab in Advanced Combined Hepatocellular-cholangiocarcinoma: an Exploratory Study
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 25
- 主要终点
- ORR
研究概览
简要总结
The Purpose of This Study is to Evaluate the Efficacy and Safety of Gemox combined with Anlotinib and Sintilimab as first-lineTherapy for Patients With advanced combined hepatocellular-cholangiocarcinoma.
详细描述
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) accounts for 0.4%-14.2% of primary hepatocellular carcinoma. As imaging and pathological diagnostic techniques for liver tumors have improved, the detection rate of cHCC-CCA puncture biopsies and surgical procedures has increased. Oxaliplatin-containing chemotherapy was previously recommended for the treatment of advanced cHCC-ICC, but its efficacy was not satisfactory. Targeted therapy and immunotherapy have made breakthroughs in both advanced HCC and CCA, providing a new direction for exploration in the treatment of advanced cHCC-CCA. Currently, targeted combination immunotherapy has become the preferred first-line treatment strategy for advanced HCC. Chemotherapy combined with immunotherapy is also the preferred first-line treatment option for advanced CCA. To balance the treatment of HCC and ICC, this study further investigates the efficacy and safety of Gemox chemotherapy combined with anlotinib and Sintilimab(anti-PD-1 monoclonal antibody) immunotherapy in advanced cHCC-ICC, to provide a new treatment strategy and reference for the clinical treatment of advanced cHCC-CCA patients.
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
- •.Age 18-75 years;
- •.Histologically or cytologically confirmed diagnosis of aCombined hepatocellular-cholangiocarcinoma;
- •.Non resectable or metastatic cHCC-ICC patients who have not received systemic treatment or first-line treatment progress (only non arotinib Targeted therapy or non GEMOX chemotherapy) in the past, and have at least one measurable lesion (RECIST v1.1);
- •.Life expectancy ≥ 3 months;
- •.ECOG PS 0-1;
- •.Child Pugh A/B ≤ 7;
- •.Adequate organ function including the following:Total bilirubin ≤1.5 times upper limit of normal (ULN),Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3×ULN,Alkaline phosphatase≤2.5×ULN (If the tumor invaded the liver, ≤3×ULN), Serum creatinine≤1.5×ULN,Serum amylase and lipase≤1.5×ULN,International standardized ratio (INR)/partial prothrombin time (PTT)≤1.5×ULN;Platelet count ≥ 75,000 /mm3.Hemoglobin (Hb) ≥ 9 g/dL.Absolute neutrophil count (ANC) ≥ 1500/mm
- •.Strict contraception.
- •.Patients must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
排除标准
- •Has a history of severe allergic reactions to chimeric, human or humanized antibodies, or fusion proteins.
- •Pregnant or lactating women, men and women of childbearing age who are unwilling or unable to take effective contraceptive measures;
- •History of other malignant tumors in the past 5 years, except for malignant tumors that have received treatment for the purpose of cure, and have no known active diseases for ≥ 5 years before the first administration, and have a low potential risk of recurrence; Fully treated non Melanoma skin cancer or malignant lentigo without disease evidence; Fully treated Carcinoma in situ, no disease evidence;
- •Moderate or higher amounts of pleural and ascitic fluid with clinical symptoms;
- •Active bleeding or abnormal coagulation function (PT>16s, APTT>43s, INR>1.5) × ULN), with a tendency to bleed or undergoing thrombolysis, anticoagulation, or antiplatelet therapy;
- •Hepatic encephalopathy;
- •Within the past 6 months, there has been a history of gastrointestinal bleeding or a clear tendency for gastrointestinal bleeding, such as known local active ulcer lesions, fecal occult blood+or above, which cannot be included in the group; If there is continuous fecal occult blood, gastroscopy should be performed;
- •Patients with severe gastroesophageal varices who require interventional treatment;
- •Untreated active hepatitis B. (Note: Hepatitis B patients who receive antiviral treatment and whose HBV Viral load is less than 2000IU/ml can be allowed to participate in the study)
- •Active hepatitis C, that is, those who are anti-HCV positive or HCV-RNA positive and have abnormal liver function;
- •Having a history of psychotropic substance abuse, unable to quit, or having a history of mental disorders;
- •Patients who received solid organ transplantation or bone marrow transplantation, or had active autoimmune diseases requiring systemic Sex therapy within 2 years before the first administration;
- •Existence of immune deficiency diseases or HIV infection;
- •There has been objective evidence that Pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia and serious impairment of lung function exist in the past or at present;
- •Major surgery on the liver or other parts has been performed within 4 weeks before the first administration, or minor surgery (such as simple resection, tooth extraction, etc.) has been performed within 1 week before the first administration;
- •Received the vaccine within 30 days before the first administration;
- •Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 4 weeks prior to the first administration;
- •For any significant clinical and laboratory abnormalities, the researchers believe that they will affect the safety evaluators, such as: active infection requiring systemic Sex therapy, uncontrollable diabetes, hypertension patients who cannot fall to the normal range (systolic pressure>140mmHg, diastolic pressure>90mmHg), myocardial infarction within 6 months, thyroid dysfunction (>NCI CTCAE v4.0 Level 1 standard) after treatment with two or less antihypertensive drugs;
- •Researchers believe that it is not suitable for inclusion in the study.
研究组 & 干预措施
Gemox combined with Anlotinib and Sintilimab
Gemox chemotherapy（gemcitabine 1g/m2 ivgtt d1,d8 +oxaliplatin 85g/m2 ivgtt d1，q3w，anlotinib (8mg po d1-14 q3w )and Sintilimab (200mg ivgtt d1 q3w)
干预措施: gemcitabine ,oxaliplatin,anlotinib,Sintilimab (Drug)
结局指标
主要结局
ORR
时间窗: Every 2 cycles (each cycle is 21 days)starting from the first cycle, and every 3 cycles after 6 cycles
Objective Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1
次要结局
- OS(Every 2 cycles(each cycle is 21 days) starting from the first cycle, and every 3 cycles after 6 cycles)
- Safety and tolerability(3 months after the last administration of drugs)
- PFS(Every 2 cycles(each cycle is 21 days) starting from the first cycle, and every 3 cycles after 6 cycles)
研究者
Zhen-Yu Ding
Director
Sichuan University