A Phase I Open-Label Dose Escalation Study to Assess the Safety and Tolerability of the BikDD Nanoparticle in Patients With Advanced Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Maximum Tolerated Dose (MTD) of BikDD Nanoparticle in Patients with Advanced Pancreatic Cancer
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of BikDD nanoparticle that can be given to patients with advanced cancer of the pancreas. The safety of this drug will also be studied.
详细描述
The Study Drug:
BikDD is a modified gene product that is designed to make cancer cells destroy themselves. Delivering BikDD in a fat molecule (a BikDD nanoparticle) may improve the delivery of the gene product into the cells. This may help to stop or slow the growth of pancreatic cancer. This is the first study using BikDD nanoparticle in humans.
Study Drug Dose Level:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of BikDD nanoparticle based on when you joined this study. Different dose levels of BikDD nanoparticle will be tested. Three (3) participants will be enrolled at each dose level. The first group of participants will receive a low dose level. Each new group will receive a higher dose level, if no intolerable side effects were seen. If intolerable side effects were seen, then the next group of participants will receive a lower dose. This will continue until the highest tolerable dose of BikDD nanoparticle is found.
The dose of study drug that you receive will never be increased. However, if you have side effects, your dose of study drug may be lowered. Your doctor will discuss with you which dose you will receive.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically or cytologically confirmed advanced pancreatic adenocarcinoma that is unresectable or metastatic.
- •Patient must have received prior gemcitabine or a regimen containing oxaliplatin, irinotecan, and 5-FU with or without leucovorin for treatment of advanced or metastatic disease, unless the patient refused such treatment. Up to two prior chemotherapeutic regimens are permitted.
- •Patients must have measurable disease including liver metastases >/= 2.0 cm amenable to percutaneous CT or U/S guided biopsy and must agree to undergo two liver biopsies.
- •Minimum of three weeks since any major surgery, radiation, or systemic anticancer therapy.
- •Any clinically significant residual adverse events from any prior anticancer therapy must have resolved to grade </= 1 or baseline as per the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.
- •Age >/=18 years. Because no dosing or adverse event data are currently available on the use of gene therapy in patients < 18 years of age, children are excluded from this study.
- •ECOG performance status 0 or
- •Adequate hematologic, hepatic and renal parameters: leukocytes >/= 3,000/microliter, absolute neutrophil count >/= 1,500/microliter, platelets >/= 100,000/microliter, hemoglobin >/= 9g/dL, total bilirubin </= 1.5 mg/dL, AST and ALT </= 3 x upper limit of normal (ULN) for subjects with documented liver metastases; AST and ALT </= 2.5 x ULN for subjects without evidence of liver metastases, creatinine </= 1.5 mg/dL and calculated creatinine clearance of >/= 60 mL/min.
- •PT/PTT are within normal limits.
- •Women of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days prior to treatment. Women must be surgically sterile or have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
- •Women of childbearing potential and men must agree to use double barrier contraception prior to study entry and continuing for 30 days after the last dose of study drug.
- •Signed written informed consent/authorization form.
排除标准
- •Prior treatment with any investigational drug within the preceding 3 weeks of Cycle 1, Day
- •Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases (Brain imaging studies are not required if the patient does not have a history of brain metastases and has no neurological signs or symptoms).
- •Other malignancies within the past 3 years of Cycle 1, Day 1 except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
- •Patients who have any known severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.
- •A known history of HIV seropositivity.
- •Women who are pregnant or breast feeding.
- •History of MI within 6 months of Cycle 1, Day 1, angina, history of arrhythmias on active therapy, patients with LV ejection fraction </= 50%.
结局指标
主要结局
Maximum Tolerated Dose (MTD) of BikDD Nanoparticle in Patients with Advanced Pancreatic Cancer
时间窗: Weekly during 28 day cycles
The maximum tolerated dose (MTD) is defined as the maximal achievable dose level at which \< 1/6 enrolled patients experiences dose-limiting toxicity.
Dose-Limiting Toxicity (DLT)
时间窗: Continuously during 28 day cycles
Dose-limiting toxicity (DLT) defined as: Any ≥ grade 3 hematologic and non-hematologic toxicity as per NCI CTCAE v. 4.0 with the following exceptions: 1. Grade 3 or 4 lymphopenia unless persistent for \>14 days or associated with single oral temperature of \>38.3°C (101°F) or temp \> 38°C (100.4°F) measured on two separate occasions one hour apart. 2. Adverse events (Grade 3 or greater) for which a clinical cause unrelated to study drug is evident will not be considered DLTs. These will include: obstructive jaundice from stent occlusion, narcotic-induced constipation if symptom is present prior to study enrollment, anorexia or cachexia if present prior to study enrollment. 3. Delay of Dose \> 14 days due to toxicity.
次要结局
未报告次要终点