Randomized, Placebo-controlled, Double-blind Phase II/III Trial of Oral Isoquercetin to Prevent Venous Thromboembolic Events in Cancer Patients.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 试验地点
- 11
- 主要终点
- Percent Change in D-dimer Value
研究概览
简要总结
This research study is evaluating a drug called isoquercetin to prevent venous thrombosis (blood clots), in participants who have pancreas, non small cell lung cancer or colorectal cancer.
详细描述
- This research study is a Phase II/III clinical trial.
--The goal of this trial is to evaluate if isoquercetin can prevent blood clots in patients with pancreas, non small cell lung cancer or colorectal cancer. In the Phase II part of this study, the investigators are looking for the dose of isoquercetin to reduce D-dimer and demonstrate safety.
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Phase III Endpoint and Treatment Plan
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Primary Endpoint for Phase III portion of protocol: Cumulative incidence of VTE.
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Following the completion of the phase II portion, enrolled patients will be randomized 1:1 to Arm C (isoquercetin) or Arm D (placebo). The dose for Arm C will be determined after evaluation of the Phase II portion of the trial. The protocol will be amended when the decision is made whether to proceed to Phase III and what dose to use for Arm C. The study will be double-blinded to treatment arm. Lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.
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At BIDMC, optional blood draw will be performed at time 0 and 4 hours following the first dose of study drug.
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
- •Participants must meet the following criteria on screening examination to be eligible to participate in phase 2 and 3 of the study:
- •Participants must have histologically confirmed malignancy that is metastatic or currently unresectable.
- •Eligible malignancies include:
- •Adenocarcinoma of the pancreas (currently unresectable or metastatic)
- •Colorectal (stage IV)
- •Non-small cell lung cancer (currently unresectable stage III or stage IV)
- •Receiving or scheduled to receive first or second line chemotherapy (within 30 days of registration)
- •Minimum age 18 years. Because limited dosing or adverse event data are currently available on the use of isoquercetin in participants <18 years of age, children are excluded from this study but will be eligible for future pediatric isoquercetin trials.
- •Life expectancy of greater than 4 months.
- •ECOG performance status ≤2 (see Appendix B ).
- •Patient must be able to swallow capsules (phase III only)
- •Participants must have preserved organ and marrow function as defined below:
- •Absolute neutrophil count ≥1,000/mcL
- •Platelets ≥ 90,000/mcL
- •PT and PTT ≤ 1.5 x upper limit of normal
- •Total bilirubin < 2.0 mg/dl
- •AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal Creatinine < 2.0 mg/dl
- •The effects of isoquercetin on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; 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.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Participants may not be receiving any other study agents.
- •Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- •Prior history of documented venous thromboembolic event within the last 2 years (excluding central line associated events whereby patients completed anticoagulation).
- •Active bleeding or high risk for bleeding (e.g. known acute gastrointestinal ulcer)
- •History of significant hemorrhage (requiring hospitalization or transfusion) outside of a surgical setting within the last 24 months
- •Familial bleeding diathesis
- •Known diagnosis of disseminated intravascular coagulation (DIC)
- •Currently receiving anticoagulant therapy
- •Current daily use of aspirin (>81mg daily), Clopidogrel (Plavix), cilostazol (Pletal), aspirin-dipyridamole (Aggrenox) (within 10 days) or considered to use regular use of higher doses of non-steroidal anti-inflammatory agents as determined by the treating physician (e.g ibuprofen > 800 mg daily or equivalent).
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Known intolerance of niacin or ascorbic acid (including known G6PD deficiency)
- •Pregnant women are excluded from this study because isoquercetin is a PDI inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with isoquercetin, breastfeeding should be discontinued if the mother is treated with isoquercetin. These potential risks may also apply to other agents used in this study.
研究组 & 干预措施
Cohort A - Isoquercetin
-- Cohort A: 500 mg, Once daily, 28 days
- For both cohorts A and B, lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.
干预措施: Isoquercetin (Drug)
Cohort B - Isoquercetin
--Cohort B: 1000 mg, Once daily, 28 days
- For both cohorts A and B, lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.
干预措施: Isoquercetin (Drug)
结局指标
主要结局
Percent Change in D-dimer Value
时间窗: Baseline, 56 Day
D-dimer concentrations will be compared for each patient at day 0 and day 56 by a paired-t test analysis. Analysis will be performed on an intention to treat basis for patients who undergo randomization and completed the baseline and day 56 D-dimer assessments.
次要结局
- Number of Participants With Hemorrhage(study visits until day 56)
- Cumulative Incidence of VTE at 56 Days(56 days)
研究者
Jeffrey Zwicker, MD
Principal Investigator
Beth Israel Deaconess Medical Center