A Randomized, Placebo-Controlled, Double-Blind Phase 3 Trial Comparing, Relative to Placebo, the Effect of Kinisoquin™ on Thromboembolic Events in Patients With Metastatic or Locally Advanced Pancreatic Cancer (CATIQ P3)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 480
- 试验地点
- 3
- 主要终点
- Effectiveness of Kinisoquin™
研究概览
简要总结
The aim of this Phase 3 study is to evaluate the efficacy of Kinisoquin™ as compared to the placebo in prevention of thromboembolic events in patients with metastatic or locally advanced pancreatic cancer.
详细描述
Approximately one-third of all pancreatic cancer patients suffer from a venous thromboembolism (VTE). The greatest risk of thrombosis is observed in the first three months following the start of chemotherapy. The development of distant metastasis in pancreatic cancer increases the risk of VTE approximately 4-fold.
Kinisoquin™ is a more bioavailable form of quercetin, a naturally occurring flavonol, intended to prevent thromboembolic events in cancer patients. The aim of this study is to evaluate the efficacy of Kinisoquin™ in prevention of thromboembolic events in patients with metastatic or locally advanced pancreatic cancer.
This trial is a randomized, placebo-controlled, double-blinded, Phase 3 trial in metastatic or locally advanced pancreatic cancer patients who are initiating chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
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 have histological or cytological confirmed pancreatic adenocarcinoma malignancy that is metastatic (including recurrent with distant metastases) or locally advanced.
- •Receiving first line chemotherapy (within 45 days of first dose of study drug) Note: subjects must be either initiating first systemic cancer therapy regimen following initial diagnosis or initiating first cycle of chemotherapy for disease recurrence.
- •Minimum age 18 years.
- •Life expectancy of greater than 4 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Participants must have preserved organ and marrow function as defined by:
- •Platelet count ≥ 100,000/mcL.
- •Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5x institutional upper limit of normal (ULN).
- •Total bilirubin ≤ 3x ULN without liver metastases and < 5x ULN in presence of liver metastases.
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3x ULN without liver metastases and < 5x ULN in the presence of liver metastases
- •Estimated creatinine clearance (CrCl > 30 mL/min).
- •Willingness of women of child-bearing potential and men to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation until at least 4 weeks after study completion.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Participants with known brain metastases
- •Prior history of documented thromboembolic event within the last 12 months (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 (> 100mg 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 > 800mg 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 to the active ingredient of Kinisoquin™, isoquercetin, nicotinic acid, or ascorbic acid (including known G6PD deficiency)
- •Females of child-bearing potential who are lactating, have a positive pregnancy test at Screening, or are unwilling to use acceptable contraception prior to study entry and for the duration of study participation until at least 4 weeks after study completion.
- •Participation in other clinical trials The study is open to any individual who has a metastatic or locally advanced pancreatic adenocarcinoma malignancy without discrimination based on race, religion, political affiliation, or other criteria.
研究组 & 干预措施
Placebo
Patients in this group will be administered placebo orally at 8 capsules per day for 16 weeks (4 capsules in the morning and 4 capsules in the evening).
干预措施: Placebo (Drug)
Kinisoquin™ 1000mg
Initially, patients will be randomized on a 1:1:1 basis to Kinisoquin™ 1000mg, Kinisoquin™ 2000mg or matching placebo daily. Patients in the 1,000 mg group will receive Kinisoquin™ at a total daily dose of 1,000 mg, administered orally as two 250 mg Kinisoquin™ capsules and two placebo capsules in the morning, and two 250 mg Kinisoquin™ capsules and two placebo capsules in the evening (total of 8 capsules daily) for 16 weeks.
An interim analysis will be performed when 26 positively adjudicated primary endpoint events have been attained across all three arms and the best performing dose will be identified and a sample size reassessment performed. Thereafter, randomization to the study will continue only for the selected dose and placebo on a 1:1 basis.
干预措施: Kinisoquin™ (Drug)
Kinisoquin™ 2000mg
Initially, patients will be randomized on a 1:1:1 basis to Kinisoquin™ 1000mg, Kinisoquin™ 2000mg or matching placebo daily. Patients in the 2,000 mg group will receive Kinisoquin™ at a total daily dose of 2,000 mg, administered orally as four 250 mg Kinisoquin™ capsules in the morning and four 250 mg Kinisoquin™ capsules in the evening (total of 8 capsules daily) for 16 weeks.
An interim analysis will be performed when 26 positively adjudicated primary endpoint events have been attained across all three arms and the best performing dose will be identified and a sample size reassessment performed. Thereafter, randomization to the study will continue only for the selected dose and placebo on a 1:1 basis.
干预措施: Kinisoquin™ (Drug)
结局指标
主要结局
Effectiveness of Kinisoquin™
时间窗: 16 weeks
The time to the first positively adjudicated thromboembolic event (TE) over 16 weeks of treatment in patients treated with Kinisoquin™ compared with placebo.
次要结局
- Risk of TE(16 weeks)
- Catheter-related TEs(16 weeks)
- Risk of major hemorrhage(16 weeks)
- Risk of clinically relevant non-major bleeding(16 weeks)
- Progression-Free Survival (PFS)(12 months)
- Overall Survival (OS)(24 Months)