A Phase I Study of NH002-mediated Sonoporation With Nanoliposomal Irinotecan, Leucovorin, and 5-Fluorouracil in Pancreatic Ductal Adenocarcinoma Patients With Liver Metastasis
概览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- AE
概览
简要总结
This is a phase I study that will enroll patients with pancreatic cancer and liver metastasis who have failed prior gemcitabine-based chemotherapy. Patients will be treated with nanoliposomal irinotecan plus 5-FU and leucovorin and NH002-based sonoporation to the liver metastasis.
详细描述
With dose escalation under the 3+3 phase I design, NH002-based sonoporation will be performed in 4 cohorts. In cohort 1, NH002 will be given with one short course of sonoporation (on Cycle 1 Day 1). In cohort 2, NH002 will be given with one long course of sonoporation (on Cycle 1 Day 1). In cohort 3, NH002 will be given with two long courses of sonoporation (on Cycle 1 Day 1 and Day 2). In cohort 4, NH002 will be given with three long courses of sonoporation (on Cycle 1 Days 1, 2, and 3). During the NH002-based sonoporation, chemotherapy with standard dose of nanoliposomal irinotecan plus 5-FU and leucovorin will be administered concomitantly. The primary endpoint is safety parameters and to determine the dose-limiting toxicity and maximum tolerated dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Dated and signed informed consent
- •Either sex, aged 18 to 80 years old (inclusive) at the date of consent
- •With histologically or cytologically confirmed PDAC
- •With life expectancy at least 12 weeks
- •Two or more liver metastatic lesions; of them, at least one lesion with the longest diameter (measured on computed tomography \[CT\] or Magnetic resonance imaging \[MRI\]) at least 1 cm and not more than 5 cm as well as a depth not more than 7 cm from the skin to the lesion center, and considered feasible for sonoporation by the investigator
- •\- Note: The number of liver metastatic lesions with the longest diameter at least 1 cm should be no more than
- •Has failed frontline gemcitabine-based chemotherapy and is prepared for an application of NHI-reimbursed nal-IRI, LV, and 5-FU treatment
- •Has not received previous radiotherapy, local therapy (e.g., radiofrequency ablation, irreversible electroporation, etc.), or cell therapy (autologous or allogenic) for PDAC
- •Has recovered from all treatment-related toxicities or resolved to no greater than grade 1, based on common terminology criteria for adverse events (CTCAE) v.5.0, before enrollment
- •With an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity within 28 days before screening
- •Presence of diarrhea at least grade 2 based on CTCAE v.5.0
- •Concomitant systemic infection requiring treatment
- •Clinically significant co-morbid medical conditions, including cardiovascular disease, such as:
- •Myocardial infarction within 180 days before screening
- •Uncontrollable angina pectoris within 180 days before screening
- •New York Heart Association (NYHA) Class III or IV congestive heart failure
- •Uncontrollable hypertension despite appropriate treatment (e.g., systolic blood pressure at least 150 mmHg or diastolic blood pressure at least 90 mmHg lasting 24 hours or more)
- •Arrhythmia requiring treatment
- •Prior organ allograft or allogeneic bone marrow transplantation
研究组 & 干预措施
One short sonoporation
one short course of sonoporation (on Cycle 1 Day 1)
- NH002: 1 dose
- sonoporation: 1 course (10 min)
干预措施: nanoliposomal irinotecan+5-FU+leucovorin (Drug)
One short sonoporation
one short course of sonoporation (on Cycle 1 Day 1)
- NH002: 1 dose
- sonoporation: 1 course (10 min)
干预措施: NH002 (Perflutren Lipid Microspheres) Injectable Suspension (Drug)
One short sonoporation
one short course of sonoporation (on Cycle 1 Day 1)
- NH002: 1 dose
- sonoporation: 1 course (10 min)
干预措施: Aco Apache Ultrasound (Device)
One long sonoporation
one long course of sonoporation (Cycle 1, Day 1)
- NH002: 2 doses
- sonoporation: 2 courses (20 min)
干预措施: nanoliposomal irinotecan+5-FU+leucovorin (Drug)
One long sonoporation
one long course of sonoporation (Cycle 1, Day 1)
- NH002: 2 doses
- sonoporation: 2 courses (20 min)
干预措施: NH002 (Perflutren Lipid Microspheres) Injectable Suspension (Drug)
One long sonoporation
one long course of sonoporation (Cycle 1, Day 1)
- NH002: 2 doses
- sonoporation: 2 courses (20 min)
干预措施: Aco Apache Ultrasound (Device)
two long sonoporation
two long courses of sonoporation (Cycle 1, Day 1 & 2)
- NH002: 2 doses, D1 & D2
- sonoporation: 2 courses (20 min), D1 & D2
干预措施: nanoliposomal irinotecan+5-FU+leucovorin (Drug)
two long sonoporation
two long courses of sonoporation (Cycle 1, Day 1 & 2)
- NH002: 2 doses, D1 & D2
- sonoporation: 2 courses (20 min), D1 & D2
干预措施: NH002 (Perflutren Lipid Microspheres) Injectable Suspension (Drug)
two long sonoporation
two long courses of sonoporation (Cycle 1, Day 1 & 2)
- NH002: 2 doses, D1 & D2
- sonoporation: 2 courses (20 min), D1 & D2
干预措施: Aco Apache Ultrasound (Device)
three long sonoporation
three long courses of sonoporation (Cycle 1, Day 1, 2 & 3)
- NH002: 2 doses; D1, D2 & D3
- sonoporation: 2 courses (20 min); D1, D2 & D3
干预措施: nanoliposomal irinotecan+5-FU+leucovorin (Drug)
three long sonoporation
three long courses of sonoporation (Cycle 1, Day 1, 2 & 3)
- NH002: 2 doses; D1, D2 & D3
- sonoporation: 2 courses (20 min); D1, D2 & D3
干预措施: NH002 (Perflutren Lipid Microspheres) Injectable Suspension (Drug)
three long sonoporation
three long courses of sonoporation (Cycle 1, Day 1, 2 & 3)
- NH002: 2 doses; D1, D2 & D3
- sonoporation: 2 courses (20 min); D1, D2 & D3
干预措施: Aco Apache Ultrasound (Device)
结局指标
主要结局
AE
时间窗: within 28 days (Cycle 1)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
MTD
时间窗: within 28 days (cycle 1)
To determine the maximum tolerated dose of NH002 in the 3+3 design according to assessment of dose-limiting toxicities with CTCAE v 5.0
次要结局
未报告次要终点