Double-blind, Placebo-controlled, Randomized, Dose-escalating, Multi-center, Phase 1 Study to Assess the Safety and Tolerability of ART-123 With Leucovorin/5-fluorouracil/Oxaliplatin and Bevacizumab in Metastatic Colorectal Cancer Patients
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 77
- 试验地点
- 32
- 主要终点
- Number and Percentage of Participants with Bleeding Events
研究概览
简要总结
To evaluate the safety and tolerability of ART-123 in patients with metastatic colorectal cancer who receive oxaliplatin-containing chemotherapy and bevacizumab
详细描述
To compare the safety and tolerability of ART-123 to placebo in patients with metastatic colorectal cancer who receive oxaliplatin-containing chemotherapy and bevacizumab
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)
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
- •18 years of age or older
- •Metastatic colorectal cancer; pathologically confirmed adenocarcinoma of the colon or rectum
- •ECOG performance status of 0 or 1
- •The most recent laboratory findings (including for liver and kidney) within 14 days prior to randomization remain within acceptable ranges Willingness of the patient and the sexual partner to use a highly effective contraceptive method during the course of the study
- •Able to sufficiently understand the clinical study and give written informed consent
排除标准
- •History of major hemorrhage
- •High risk of hemorrhage
- •History of other malignancies
- •Active ulcer
- •Patients using anti-coagulants and fibrinolytic drugs
- •Active Hepatitis B, or known HBs antigen positive
- •Prior treatment history with thrombomodulin alfa
- •Administration of another investigational medicinal product within 30 days prior to randomization
- •Patient is pregnant (positive urine human chorionic gonadotropin) or breastfeeding or intends to get pregnant during the Treatment period
- •Patients otherwise deemed as inappropriate to participate in the study by the Investigator
研究组 & 干预措施
Medium Dose
Lyophilized ART-123 reconstituted with sterile water for injection and administered by intravenous infusion over approximately 30 minutes prior to chemotherapy on Day 1 of cycle (for up to 3 cycles including bevacizumab)"
干预措施: thrombomodulin alfa (Drug)
Lowest Dose
Lyophilized ART-123 reconstituted with sterile water for injection and administered by intravenous infusion over approximately 30 minutes prior to chemotherapy on Day 1 of cycle (for up to 3 cycles including bevacizumab)
干预措施: thrombomodulin alfa (Drug)
Low Dose
Lyophilized ART-123 reconstituted with sterile water for injection and administered by intravenous infusion over approximately 30 minutes prior to chemotherapy on Day 1 of cycle (for up to 3 cycles including bevacizumab)"
干预措施: thrombomodulin alfa (Drug)
High Dose
Lyophilized ART-123 reconstituted with sterile water for injection and administered by intravenous infusion over approximately 30 minutes prior to chemotherapy on Day 1 of cycle (for up to 3 cycles including bevacizumab)"
干预措施: thrombomodulin alfa (Drug)
Highest Dose
Lyophilized ART-123 reconstituted with sterile water for injection and administered by intravenous infusion over approximately 30 minutes prior to chemotherapy on Day 1 of cycle (for up to 3 cycles including bevacizumab)"
干预措施: thrombomodulin alfa (Drug)
Placebo
Lyophilized placebo reconstituted with sterile water for injection and administered by intravenous infusion over approximately 30 minutes prior to chemotherapy on Day 1 of cycle (for up to 3 cycles including bevacizumab)"
干预措施: Placebo (Drug)
结局指标
主要结局
Number and Percentage of Participants with Bleeding Events
时间窗: From start of first IMP dose (Cycle 1, Day 1) through EOT visit; planned for 6 weeks
Number and percentage of participants experiencing bleeding events
Number and Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)
时间窗: From start of first IMP dose (Cycle 1, Day 1) through End of Treatment (EOT) visit; planned for 6 weeks
Number and percentage of participants experiencing one or more adverse events which occurred or worsened in severity after the start of the first dose of investigational medicinal product (IMP)
Number and Percentage of Participants with Serious TEAEs
时间窗: From start of first IMP dose (Cycle 1, Day 1) through EOT visit; planned for 6 weeks
Number and percentage of participants experiencing one or more serious adverse events which occurred or worsened in severity after the start of the first dose of IMP
Number and Percentage of Participants with Serious Bleeding Events
时间窗: From start of first IMP dose (Cycle 1, Day 1) through EOT visit; planned for 6 weeks
Number and percentage of participants with bleeding events that represent serious adverse events
Number and Percentage of Participants with Abnormal Serum Chemistry Results
时间窗: 6 weeks
Descriptive statistics will summarize the following by cohort: aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, lactate dehydrogenase, total bilirubin, total protein, albumin, blood urea nitrogen, creatinine, glucose, and electrolytes (sodium, potassium, chloride)
Number and Percentage of Participants with Abnormal Coagulation Panel Results
时间窗: 6 weeks
Descriptive statistics will summarize the following by cohort: international normalized ratio (INR), activated partial thromboplastin time (APTT)
Number and Percentage of Participants with Abnormal Qualitative Urinalysis Results
时间窗: 6 weeks
Qualitative summary of the following by cohort: protein, glucose, and occult blood
Number and Percentage of Participants with TEAEs Leading to Death
时间窗: From start of first IMP dose (Cycle 1, Day 1) through EOT visit; planned for 6 weeks
Number and percentage of participants with TEAEs that resulted in death
Number and Percentage of Participants with TEAEs Leading to IMP Discontinuation
时间窗: From start of first IMP dose (Cycle 1, Day 1) through planned third IMP dose; planned for 4 weeks
Number and percentage of participants with TEAEs that lead to discontinuation of IMP
Number and Percentage of Participants with Dose Limiting Toxicity (DLT)
时间窗: From start of first IMP dose (Cycle 1, Day 1) until the start of the third IMP dose; planned for 4 weeks
Number and percentage of participants experiencing DLT
Number and Percentage of Participants with Abnormal Complete Blood Count (CBC) Results
时间窗: 6 weeks
Descriptive statistics will summarize the following by cohort: red blood cell count, hemoglobin, hematocrit, white blood cell count, white blood cell differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), and platelet count
Number and Percentage of Participants with Abnormal Vital Signs
时间窗: 6 weeks
Descriptive statistics will summarize the following by cohort: body temperature, pulse, and blood pressure
Number and Percentage of Participants with Anti-ART-123 Antibodies
时间窗: 6 weeks
Number and Percentage of Participants with detectable anti-ART-123 antibodies; samples testing positive for anti-ART-123 antibodies will be tested for the presence of neutralizing antibodies
次要结局
- Plasma Concentrations of Thrombomodulin(Cycle 1, Day 1 (each cycle is 14 days))
- Plasma Concentrations of 5-fluorouracil (5-FU)(Cycle 1, Day 1 (each cycle is 14 days))
- Plasma Concentrations of Oxaliplatin(Cycle 1, Day 1 and Cycle 3, Day 1 (each cycle is 14 days))
- Serum Concentrations of Bevacizumab(Cycle 1, Day 1 and Cycle 3, Day 1 (each cycle is 14 days))