A Phase II Trial to Evaluate the Efficacy of Recombinant Human IL-21-expressing Oncolytic Vaccinia Virus Injection (hV01) in Patients With Advanced Pancreatic Tumors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Anti-tumor activity of hV01: overall response rate (ORR).
研究概览
简要总结
The main goal of this clinical trial is to preliminary evaluate the efficacy of recombinant human IL-21-expressing oncolytic vaccinia virus injection (hV01) in patients with advanced pancreatic cancer.And the secondary purpose is to evaluate the safety of hV01.
详细描述
This is a single-site, single-arm, open-label,exploratory phase Ⅱa study. Based on the safety results of the completed phase I clinical trial of hV01 , 8.0x10 ^ 8 PFU was selected as a dose level of the dosage for each administration in this clinical trial, hV01 will be administered with twice per cycle (on day 1 and day 15), efficacy evaluation will be conducted on day 28, and every 28 days as a treatment cycle,during which safety will be observed.
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
- •Signing an informed consent form.
- •Men or women aged 18 to 75 years.
- •Histologically and/or cytologically confirmed advanced malignant advanced pancreatic tumors refractory or failed to respond to standard therapy (including disease progression and/or intolerable toxicities).
- •At least one measurable lesion according to RECIST v1.1 criteria, which can be injected intratumorally either directly or with the assistance of Endoscopic ultrasound. The baseline longest diameter (shortest diameter for lymph node lesions) of the lesion targeted for injection should be more than 1.5 cm, and the lesion also meets the requirements of the relevant dosing volume.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Required baseline laboratory data include:
- •a) Hematology: absolute neutrophil count (ANC) ≥ 1.5×10^9/L, platelet (PLT) count ≥ 75×10^9/L, hemoglobin (Hb) ≥90 g/L (without supportive therapy within 14 days prior to laboratory test); b) Liver function: serum total bilirubin (TBIL) ≤1.5×ULN (or ≤3×ULN for patients with liver metastasis); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3×ULN (or<5×ULN for patients with primary liver cancer or liver metastasis); c) Renal function: serum creatinine (Cr) ≤1.5×ULN, and creatinine clearance (Cockcroft-Gault method) ≥45 mL/min. For men: creatinine clearance = [[140-age(yr)]×weight (kg)]/[0.818×creatinine (μmol/L)]; For women: creatinine clearance = [[140-age(yr)]×weight (kg)×0.85]/[0.818×creatinine (μmol/L)]; d) Coagulation test: activated partial thromboplastin time (APTT) ≤1.5×ULN; international normalized ratio (INR) ≤1.5×ULN.
- •Female patients of childbearing age must have a negative serum pregnancy test. Female patients of childbearing age and male patients whose partners are of childbearing age must agree to use medically approved contraceptive measures (hormonal or barrier methods or abstinence) throughout the treatment period and also within 3 months after the last dose of the investigational drug. Male patients must also avoid sperm donation.
排除标准
- •Receiving any of the following anti-tumor treatments within a specified time period:
- •a) Systemic anti-tumor treatment, including chemotherapy, large-molecule targeted therapy, immunotherapy, and endocrine therapy within 4 weeks before first dose (within 6 weeks of dosing for nitrosourea or mitomycin C); b) Small-molecule targeted therapy within 2 weeks before first dose or within 5 half-lives of the small-molecule targeted drug (whichever is longer); c) Traditional Chinese medicine or Chinese herbal medicine used as anti-tumor agent within 2 weeks before first dose; d) Radiotherapy (excluding palliative radiotherapy) within 2 weeks before first dose; e) Prior oncolytic virus treatment.
- •Acute toxic effects from prior treatments not resolved to Common Terminology Criteria for Adverse Events (CTCAE, v5.0) grade 1 or below, except for toxicities deemed safe by the investigator, such as alopecia.
- •Patients with clinical symptoms of central nervous system (CNS) metastasis or meningeal metastasis, or other evidence indicating that CNS or meningeal metastases are not controlled.
- •Known or suspected active autoimmune diseases (including but not limited to systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, and Hashimoto's thyroiditis).
- •History of severe cardiovascular and cerebrovascular diseases, including:
- •a) Acute coronary syndrome (including myocardial infarction, severe or unstable angina), myocarditis, congestive heart failure, cerebrovascular accidents, or other cardiovascular events of CTCAE (v5.0) grade 3 or higher within 12 months of dosing; b) Severe arrhythmia requiring clinical intervention (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes), corrected QT interval (QTc) >450 ms for males or >470 ms for females, or a family history of long QT syndrome; c) New York Heart Association (NYHA) classification of class II or above, or left ventricular ejection fraction (LVEF) <50%; d) Uncontrolled hypertension (as judged by the investigator) or hypotension despite standard treatment.
- •Any uncontrolled active infection requiring systemic anti-infective therapy (graded 2 or higher according to CTCAE v5.0), including but not limited to active tuberculosis, sepsis, bacteremia, fungemia, and viremia.
- •Any of the following infections: human immunodeficiency virus (HIV), syphilis spirochete(TP), active hepatitis C (positive HCV RNA test) or active hepatitis B (positive HBsAg and HBV DNA ≥ 2000 IU/mL or ≥10^4 copies/mL).
- •Use of immunomodulatory drugs within 2 weeks of dosing, including but not limited to thymosin, interleukin, interferon.
- •Pregnant or lactating women.
研究组 & 干预措施
hV01 intratumoral injection
Participants will receive intratumoral injections of hV01 at the dose level of 8.0×10^8 PFU on Day 1 and Day 15 of each treatment cycle.
干预措施: Recombinant human IL-21-expressing oncolytic vaccinia virus injection (Biological)
结局指标
主要结局
Anti-tumor activity of hV01: overall response rate (ORR).
时间窗: From baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after the end of treatment.
To evaluate the overall response rate (ORR) as a measurement of tumor response and disease progression.
Anti-tumor activity of hV01: disease control rate (DCR).
时间窗: From baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after the end of treatment.
To evaluate the disease control rate (DCR) as a measurement of tumor response and disease progression.
Anti-tumor activity of hV01: duration of response (DOR).
时间窗: From baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after the end of treatment.
To evaluate the duration of response (DOR) as a measurement of tumor response and disease progression.
次要结局
- Anti-tumor activity of hV01: progression-free survival (PFS).(From baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after the end of treatment.)
- Preliminary efficacy of hV01: overall survival (OS).(From signing informed consent form until the date of death from any cause, assessed up to 2 years after the end of treatment.)
- To assess the adverse events (AEs) and tolerability of hV01.(From informed consent till 28 days after first dose.)