Liposomal Irinotecan Combined With Albumin-bound Paclitaxel for Second-line Treatment of Advanced Gastric Cancer: a Single-arm, Single-center Clinical Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 18
- 主要终点
- Maximum tolerated dose
研究概览
简要总结
Liposomal irinotecan, intravenous infusion 90min, d1:
Grade 1:50mg/m2 Grade 2:60mg/m2 Grade 3:70mg/m2 Albumin-paclitaxel, 150mg/m2, intravenous infusion, d1 DLT was observed for 2 weeks (the first cycle). The same subject received only one dose of liposomal irinotecan during the study. All subjects underwent protocol-mandated examinations during treatment to observe safety and initial efficacy. If the patient volunteers and the investigator determines that the benefits of continuing the original regimen outweigh the risks, the subject may continue to receive treatment for metastatic disease. The drug was repeated every 2 weeks for up to 6 cycles, and the albumin paclitaxel or liposomal irinotecan were withdrawn according to the patient's adverse reactions and physical status, and the remaining single-agent maintenance therapy was performed. Until there is a possibility of surgery, disease progression, intolerable toxicity or the patient withdraws informed consent (whichever comes first).
详细描述
This is a single-arm, single-center clinical study to evaluate the efficacy and safety of liposomal irinotecan combined with albumin paclitaxel regimen for second-line treatment of advanced gastric cancer. Using a "3+3" study design, 9 to 18 eligible patients with unresectable or locally advanced gastric cancer and gastroesophageal junction adenocarcinoma will receive liposomal irinotecan + albumin paclitaxel combination therapy.
Three dose groups of liposomal irinotecan 50mg/m2, 60 mg/m2 and 70 mg/m2 were preset, and a fixed dose of albumin paclitaxel (150mg/m2, intravenous infusion, d1) was administered for one cycle. The dose of liposomal irinotecan was gradually increased from the low-dose group to the high-dose group, and DLT was observed for 2 weeks (the first cycle). The same subject received only one dose of liposomal irinotecan during the study. All subjects underwent protocol-mandated examinations during treatment to observe safety and initial efficacy. If the patient volunteers and the investigator determines that the benefits of continuing the original regimen outweigh the risks, the subject may continue to receive treatment for metastatic disease. The drug was repeated every 2 weeks for up to 6 cycles, and the albumin paclitaxel or liposomal irinotecan were withdrawn according to the patient's adverse reactions and physical status, and the remaining single-agent maintenance therapy was performed. Until there is a possibility of surgery, disease progression, intolerable toxicity or the patient withdraws informed consent (whichever comes first).
Main study indicators: Maximum tolerated dose (MTD) of liposomal irinotecan in the combination regimen; Secondary study measures: dose-limiting toxicity (DLT) of liposomal irinotecan, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) .
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
- •Patients fully understand the study, voluntarily participate and sign an informed consent form (ICF)
- •Age ≥18 years
- •The expected survival time is ≥3 months
- •Patients with histologically or pathologically confirmed unresectable or locally advanced gastric cancer and gastro-oesophageal junction adenocarcinoma
- •Patients who have progressed after previous first-line treatment based on fluorouracil
- •HER-2+ is known to have been previously trastuzumab or HER-2 negative
- •According to RECIST1.1 criteria, the patient had at least one measurable target lesion
- •Eastern Cooperative Oncology Group（ECOG）Physical status score: 0-2
- •Absolute neutrophil count (ANC) ≥1.5×10^9/L, platelets ≥100×10^9/L, and hemoglobin ≥90 g/L
- •Serum creatinine ≤1.5 times the upper limit of normal value; AST and ALT ≤2.5 times the upper limit of normal (≤5 times the upper limit of normal for patients with liver invasion); Total bilirubin ≤1.5 times the upper limit of normal (≤3 times the upper limit of normal for patients with liver invasion)
- •There are no contraindications for the use of liposomal irinotecan and albumin paclitaxel
- •Women of childbearing age must have had a pregnancy test (serological) negative within 7 days prior to enrollment and be willing to use an appropriate method of contraception during the trial
- •Agree to provide histological samples
排除标准
- •Allergic reaction to any investigational drug or its ingredients
- •Patients with relapse within 6 months after previous first-line treatment with paclitaxel
- •The investigational agent was a CYP3A4 strong inducer within 2 weeks prior to initial administration, or a CYP3A4 strong depressant or UGT1A1 strong depressant within 1 week
- •Uncontrolled systemic diseases (e.g. advanced infections, uncontrolled hypertension, diabetes, etc.)
- •Imaging confirmed intestinal obstruction
- •It has uncontrollable ascites, abdominal infection and pyloric obstruction
- •Hepatitis B, hepatitis C active infection (hepatitis B surface antigen positive and hepatitis B DNA more than 1x103 copies /mL; more than 1x103 copies /mL of HCV RNA)
- •Human immunodeficiency virus (HIV) infection (HIV antibody positive)
- •Previous or current co-occurrence of other malignancies (in addition to non-melanoma basal cell carcinoma of the skin that is effectively controlled, breast/cervical carcinoma in situ, and other malignancies that have been effectively controlled without treatment within the past five years)
- •Pregnant and lactating women and patients of childbearing age who do not want to use contraception
- •The investigators determined that patients were not suitable to participate in this study
研究组 & 干预措施
Liposomal irinotecan + Albumin-paclitaxel
Liposomal irinotecan, intravenous infusion 90min, d1:
Grade 1:50mg/m2； Grade 2:60mg/m2； Grade 3:70mg/m2；
Albumin-paclitaxel, 150mg/m2, intravenous infusion, d1
干预措施: Irinotecan Hydrochloride Liposome Injection；Paclitaxel For Injection (Albumin Bound) (Drug)
结局指标
主要结局
Maximum tolerated dose
时间窗: From the recorded first dose of Liposomal irinotecan to 4 weeks after the recorded last dose of Liposomal irinotecan.
To estimate the maximum tolerated dose of liposomal irinotecan in the combination regimen based on dose-limiting toxicity
次要结局
- Dose-limiting Toxicity (DLT) of liposomal irinotecan(From the recorded first dose of Liposomal irinotecan to 4 weeks after the recorded last dose of Liposomal irinotecan.)
- Objective response rate(Data obtained up until progression, or the last evaluable assessment in the absence of progression, will be assessed up to 2 years.)
- Disease control rate(Data obtained up until progression, or the last evaluable assessment in the absence of progression, will be assessed up to 2 years.)
- Progression-free survival(Progression-free survival (PFS) analysis based on investigator assessment per RECIST 1.1, and will be assessed up to 2 years.)
- Overall survival(The time from beginning of Liposomal irinotecan treatment until death due to any cause and will be assessed up to 3 years.)