Phase IIa Trial Evaluating the Safety of Intratumoral Injection of NanoPac® in Subjects With Locally Advanced Pancreatic Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 4
- 主要终点
- Number of Subjects With Treatment Emergent Adverse Events (Safety and Tolerability)
研究概览
简要总结
Open-label, dose-escalating, Phase IIa trial of NanoPac® to treat subjects with locally advanced pancreatic adenocarcinoma via direct intratumoral injection.
详细描述
In this open-label, dose-escalating, Phase IIa trial, subjects with locally advanced pancreatic adenocarcinoma will receive intratumoral (ITU) NanoPac® (Sterile Nanoparticulate Paclitaxel) via endoscopic ultrasound-guided direct injection.
Subjects will be enrolled in sequential cohorts of NanoPac® at escalating doses, at a volume based on up to 20% of calculated tumor volume (with a maximum injection volume of 5 mL per subject). During the first phase of the trial (dose escalation), each cohort will have three subjects, with cohorts enrolled sequentially starting at the lowest concentration. Following DSMB review of the cohort data, the next cohort may begin enrolling, an additional three subjects at the current dose may be enrolled, or if the first dose does not provide adequate safety and tolerability the study may be halted.
The dose determined to be most suitable for further evaluation, defined as the highest dose with an acceptable safety and tolerability profile as determined by the Data Safety Monitoring Board (DSMB), will be the dose used in the second phase of the study which will enroll 22 additional subjects who will receive two injections of NanoPac® at the same dose one month apart. In the third phase of the study, up to 30 subjects will receive up to four injections of NanoPac at the same dose, one month apart.
Plasma samples will be taken at various time points on the day of NanoPac® injection as well as once at each of the study visits, to characterize the pharmacokinetics (PK) of ITU NanoPac®.
Subjects will be followed for 12 months after NanoPac® injection for safety, overall survival (OS), progression-free survival (PFS), CA-19-9 levels, carcinoembryonic antigen (CEA) levels, reduction in pain, and tumor response to therapy (as shown by imaging).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent;
- •Age ≥18 years;
- •Histologically/cytologically confirmed locally advanced pancreatic adenocarcinoma; at least one lesion with a diameter of at least 1.5 cm but no more than 6 cm as documented via imaging (within 6 weeks of Screening);
- •Subject not a candidate for surgery;
- •Completion of at least one standard of care IV chemotherapy course for subjects in the dose escalation phase of the study. IV chemotherapy will be initiated prior to first NanoPac injection for subjects in the second and third phases. Hematologic recovery must be confirmed prior to study entry;
- •Performance Status (ECOG) 0-1 at study entry;
- •Life expectancy of at least 3 months;
- •Adequate marrow, liver, and renal function at study entry:
- •ANC ≥ 1.5 x 109/L
- •Hemoglobin ≥ 9.5 grams/dL
- •Platelets ≥ 75 x 109/L
- •Total bilirubin ≤ 1.5x institutional ULN
- •AST/ ALT ≤ 2.5x institutional ULN
- •Creatinine ≤ 1.5x institutional ULN
- •Effective contraception if the risk of conception exists.
排除标准
- •Thrombotic or embolic events;
- •Acute or subacute intestinal occlusion;
- •History of inflammatory bowel disease;
- •Known hypersensitivity to study drugs;
- •Known drug or alcohol abuse;
- •Pregnant or breastfeeding women;
- •Previous or concurrent history of non-pancreatic malignancy except for non-melanoma skin cancer.
研究组 & 干预措施
Dose Escalation: NanoPac® 6 mg/mL
Intratumorally injected NanoPac® at a volume of up to 20% tumor volume
干预措施: NanoPac® (Drug)
Dose Escalation: NanoPac® 10 mg/mL
Intratumorally injected NanoPac® at a volume of up to 20% tumor volume
干预措施: NanoPac® (Drug)
Dose Escalation: NanoPac® 15 mg/mL
Intratumorally injected NanoPac® at a volume of up to 20% tumor volume
干预措施: NanoPac® (Drug)
Second Phase: NanoPac® at Best Dose
Intratumorally injected NanoPac® at a volume of up to 20% tumor volume. The dose administered in the second phase will be determined during the dose escalation phase. Subjects will receive two NanoPac® administrations, with the second injection administered one month after the first injection.
干预措施: NanoPac® (Drug)
Third Phase: NanoPac® at Best Dose
Intratumorally injected NanoPac® at a volume of up to 20% tumor volume. The dose administered in the third phase will be determined during the dose escalation phase. Subjects will receive four NanoPac® administrations, with the injections administered one month apart.
干预措施: NanoPac® (Drug)
结局指标
主要结局
Number of Subjects With Treatment Emergent Adverse Events (Safety and Tolerability)
时间窗: Up to Week 24 for Dose Escalation subjects; up to Week 28 for Second Phase subjects; up to 9 Months for Third Phase subjects.
Treatment Emergent Adverse Events will include laboratory assessments, physical examination findings, and vital signs.
次要结局
- Target Tumor Assessment(Week 24)
- Plasma Paclitaxel Concentration (pg/mL)(Day 1 and Week 24)
- Pain (Visual Analog Scale) Score(Day 1 (pre-injection) and Week 24)
- Serum CA19-9 Level(Day 1 (Pre-Injection) and Week 24)
- Serum CEA Levels(Day 1 (Pre-Injection) and Week 24)