A Phase 1, Multi-Center, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Minnelide™ Given Daily for 21 Days Followed by 7 Days Off Schedule in Patients With Advanced GI Tumors.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- To establish the dose of Minnelide™ recommended for future phase 2 protocol
研究概览
简要总结
The primary objective of this study is to determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of Minnelide™ and to establish the dose of Minnelide™ recommended for future phase 2 protocol
详细描述
This is a Phase 1, open label, multicenter, dose-escalation study of safety, pharmacokinetics, and pharmacodynamics of Minnelide™
Minnelide™ will be given as a single agent intravenously as a 30-minute infusion daily x 21 days followed by a 7-day rest period. One cycle will equal 28 days. Dose escalation will follow a modified Fibonacci design.
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
- •Histologically or cytologically confirmed gastrointestinal (GI) carcinoma, which has progressed on standard therapies (surgery, radiotherapy, endocrine therapy, chemotherapy), for which effective therapy is not available or for which patients are not a candidate for or intolerant of such therapies.
- •Have one or more metastatic tumors measurable on CT scan or locally advanced measurable disease that has clearly progressed after prior treatment per RECIST criteria.
- •Male and female patients at least 18 years of age
- •Laboratory data as specified:
- •Hematology: ANC >1500 cells/mm3, platelet count > 150,000 cells/mm3 and Hemoglobin > 9 g/dL
- •Hepatic: Direct bilirubin ≤1.5 X ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 X ULN. For patients with known liver metastases or liver neoplasms, then ALT or AST ≤ 5.0 X ULN is allowed
- •Renal: serum creatinine WNL or calculated creatinine clearance ≥ 50 mL/min/1.73m2 for patients with creatinine levels above institutional normal
- •Urinalysis: No clinically significant abnormalities
- •Coagulation: INR within normal limits, PTT within normal limits
- •Estimated life expectancy of at least 3 months
- •Karnofsky Performance ≥ 70%
- •A negative serum pregnancy test (if female)
- •For men and women of child-producing potential - willingness to employ appropriate contraceptive methods (including abstinence) during the study.
- •Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments.
排除标准
- •Women who are pregnant or nursing. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- •New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
- •Baseline QTc exceeding 450 msec (470 msec for females) using the Bazetts formula and/or patients receiving class 1A or class III antiarrythmic agents.
- •Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
- •Treatment with radiotherapy, chemotherapy or investigational therapy within 1 month (or 5 half lifes for cytotoxics) prior to study entry (6 weeks for nitrosoureas or Mitomycin C).
- •Known HIV, Hepatitis A, B or Hepatitis C infection
- •Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.
- •Participation in concurrent study of an investigational agent or device.
- •Unwillingness or inability to comply with procedures required in this protocol.
- •Any other condition including but not limited to major co-morbidities, which in the opinion of the investigator would render the patient ineligible.
研究组 & 干预措施
Minnelide™ 001
A Phase 1, Multi-Center, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Minnelide™ given daily for 21 days followed by 7 days off schedule in patients with Advanced GI Tumors
干预措施: Minnelide™ 001 (Drug)
结局指标
主要结局
To establish the dose of Minnelide™ recommended for future phase 2 protocol
时间窗: 24 months
Once the MTD has been determined this will be the dose going forward in phase 2 studies
To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of Minnelide™
时间窗: 24 months
The MTD will be determined using a 3 + 3 design and will continue until 2 patients at any dose level experience a DLT. A DLT will be defined as Grade 4 neutropenia lasting ≥ 5 days or Grade 3 or 4 neutropenia with fever and/or infection;Grade 4 thrombocytopenia (or Grade 3 with bleeding);Grade 3 or 4 treatment-related non-hematological toxicity (Grade 3 nausea, vomiting or diarrhea that last \> 72 hours despite maximal treatment constitutes a DLT, insufficient treatment will not constitute an exception to the DLT criteria, as this would constitute inadequate conduct of the study); Dosing delay greater than 2 weeks due to treatment-emergent AEs or related severe laboratory abnormalities.
次要结局
- To observe patients for any evidence of antitumor activity of Minnelide™ per RECIST criteria(24 months)
- To determine pharmacodynamic effect of Minnelide™ on HSP70 levels. And to explore pharmacodynamics effect of Minnelide™ on PET Scans and using Choi criteria on the CT scans.(24 months)
- To determine the pharmacokinetics of Minnelide™(24 months)