Phase I Study of Combination with TBI-1401(HF10), a Replication-competent HSV-1 Oncolytic Virus, and Chemotherapy in Patients with Stage III or IV Unresectable Pancreatic Cancer.
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study is to determine the recommended dose of TBI-1401(HF10) treatment in combination with chemotherapy (Gemcitabine + Nab-paclitaxel or TS-1) in patients with stage III or IV unresectable pancreatic cancer.
详细描述
A Phase I, open-label, multi-center study to determine the recommended dose of TBI-1401(HF10) treatment in combination with chemotherapy (Gemcitabine + Nab-paclitaxel or TS-1) in patients with stage III or IV unresectable pancreatic cancer. Patients with stage IV must failed a gemcitabine based first-line chemotherapy.
Patients with stage III will receive the repeated intratumoral injection of TBI-1401(HF10) at recommended dose at 2-week intervals in combination with intravenous infusion of 1000 mg/m^2 Gemcitabine and 125 mg/m^2 Nab-paclitaxel at weekly for 3 weeks followed by 1 week rest.
Patients with stage IV will receive the repeated intratumoral injection of TBI-1401(HF10) at recommended dose at 2-week intervals in combination with oral of 40 - 60 mg TS-1 at twice daily for 4 weeks followed by 2 weeks rest.
Patients will receive the combination therapy of TBI-1401(HF10) + chemo for up to 1 year if eligible for treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically or cytologically confirmed unresectable pancreatic cancer (stage III or IV) based on the General Rules for the Study of Pancreatic Cancer (The 7th edition), and never received anti-cancer therapy (radiation therapy, chemotherapy, immunotherapy, surgery, clinical trials).
- •Patients with primary lesion will be intratumorally injectable for TBI-1401(HF10) by EUS (endoscopic ultrasound).
- •Patients must be ≧20 years of age.
- •Patients must have at least one measurable lesion evaluated by Computed Tomography (CT) scan on RECIST ver.1.1 at pre-treatment.
- •Patients must have a life expectancy ≧12 weeks.
- •Patients must have an ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0-
- •Patients demonstrated adequate organ function (≦7 days prior to treatment).
- •Females of childbearing potential must have a negative urine or serum pregnancy test within 1 week prior to start of treatment.
- •Patients must be able to understand the study and willing to sign a written informed consent document.
排除标准
- •Patients receiving anti-herpes medication within 1 week prior to TBI-1401(HF10) treatment (except local treatment such as ointment).
- •Patients with a significant tumor bleeding or coagulation abnormality that could not treat intratumoral injection or biopsy in safe.
- •Patients with clinically evident Hepatitis B surface antigen (HBs) positive, Hepatitis C virus (HCV) antibody positive and HSV-RNA positive, Human Immunodeficiency Virus (HIV) antibody positive.
- •Patients with the active symptom of Epstein-Barr virus (EBV) infection.
- •Patients with active CNS metastases.
- •Patients with ascites, except acceptable mild ascites.
- •Patients with multiple cancer.
- •Patients need to treat anticoagulant or antiplatelet agent.
- •Patients has a history of allergy for CT contrast agent, live vaccine, any drug excipients, Nab-paclitaxel, Gemcitabine, or any study drugs.
研究组 & 干预措施
TBI-1401(HF10) + Gem/nab-PTX
1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and 1000 mg/m^2 Gemcitabine and 125 mg/m^2 Nab-paclitaxel injected by intravenous infusions.
干预措施: TBI-1401(HF10) (Biological)
TBI-1401(HF10) + Gem/nab-PTX
1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and 1000 mg/m^2 Gemcitabine and 125 mg/m^2 Nab-paclitaxel injected by intravenous infusions.
干预措施: Gemcitabine (Drug)
TBI-1401(HF10) + Gem/nab-PTX
1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and 1000 mg/m^2 Gemcitabine and 125 mg/m^2 Nab-paclitaxel injected by intravenous infusions.
干预措施: Nab-paclitaxel (Drug)
TBI-1401(HF10) + TS-1 (primary)
1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the primary tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and TS-1 administered by oral.
干预措施: TBI-1401(HF10) (Biological)
TBI-1401(HF10) + TS-1 (primary)
1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the primary tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and TS-1 administered by oral.
干预措施: TS-1 (Drug)
TBI-1401(HF10) + TS-1 (primary and meta)
1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the primary tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and hepatic metastasis in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection or percutaneous injection and TS-1 administered by oral.
干预措施: TBI-1401(HF10) (Biological)
TBI-1401(HF10) + TS-1 (primary and meta)
1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the primary tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and hepatic metastasis in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection or percutaneous injection and TS-1 administered by oral.
干预措施: TS-1 (Drug)
结局指标
主要结局
Dose Limiting Toxicity (DLT)
时间窗: Through 1st TBI-1401(HF10) injection to before 3rd injection (basically 4 weeks).
Determine the recommended dose of TBI-1401(HF10) in combination with Gemcitabine and Nab-paclitaxel.
次要结局
- Objective response rate (ORR) by irRECIST(At 16 weeks and through study completion (up to 1 year).)
- Adverse Events (AEs)(Through 1st TBI-1401(HF10) injection to study completion (up to 13 month).)
- Progression-free survival (PFS) by irRECIST(Through disease progression (up to 1 year).)
- Objective response rate (ORR) by RECIST(At 16 weeks and through study completion (up to 1 year).)
- Progression-free survival (PFS) by RECIST(Through disease progression (up to 1 year).)