Safety and Tolerability of ASLAN001 in Combination With Cisplatin and 5-FU or Cisplatin and Capecitabine
Phase I Study to Evaluate the Safety and Tolerability of ASLAN001 in Combination With Cisplatin and 5-Fluorouracil or Cisplatin and Capecitabine
研究概览
地位
条件
详细说明
This is an open-label, Phase I, dose escalation study of ASLAN001 given in combination with Regimen A or Regimen B, in patients with metastatic solid tumors, eligible to receive the cisplatin/5-fluorouracil or cisplatin/capecitabine regimen.
Dose of ASLAN001 starts from 400mg BID; then, dose escalation to 500mg BID or dose de-escalation to 300mg BID will depend on DLTs observed in cohort.
Regimen A: Depends on preferred medical practice, Cohort 1A will receive ASLAN001 400 mg BID in combination with cisplatin 80 mg/m2 IV infusion and 5 fluorouracil 800 mg/m2/day IV infusion for 5 days every 3 weeks; or will receive ASLAN001 400 mg BID in combination with Cisplatin 35 mg/m2 24-hour infusion for day 1 and day 8, 5-fluorouracil 2,000 mg/m2 and Leucovorin 300mg/m2 24-hour infusion for day 1, day 8 and day 15 every 4 weeks.
Regimen B: Cohort 1B will receive ASLAN001 400 mg BID in combination with cisplatin 80 mg/m2 IV infusion and oral capecitabine 1,000 mg/m2 BID for 14 days every 3 weeks.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Male or female patients 20 years of age or older at the time written informed consent is obtained.
Regimen A: Patients with metastatic solid tumors eligible for treatment with cisplatin and 5-fluorouracil. The standard dose and schedule of cisplatin and 5-fluorouracil will be according to the preference of investigators and institutions.
Regimen B: Patients with metastatic solid tumors eligible for treatment with cisplatin in combination with capecitabine.
- Patients with a partial gastrectomy may be allowed to participate in the study as long as they can take oral medications and meet all other inclusion/exclusion criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate organ and hematological function as evidenced by the following laboratory studies within 14 days prior to enrolment:
Hematological function, as follows:
- Absolute neutrophil count ≥ 1.5 x 109/L.
- Platelet count ≥ 100 x 109/L.
- Hemoglobin ≥ 9 g/dL.
Coagulation function, as follows:
- Partial thromboplastin time or activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN) per institutional laboratory normal range.
- International normalized ratio ≤ 1.5.
Renal function, as follows:
• Creatinine clearance ≥ 50 mL/min as calculated by Cockcroft-Gault formula.
Hepatic function, as follows:
- Total bilirubin ≤ 1.5 x ULN.
- AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present).
Exclusion Criteria:
- Patients with persistent gastric outlet obstruction, complete dysphagia or feeding jejunostomy.
- Patients receiving proton pump inhibitors or H2 antagonists for established, symptomatic gastro duodenal ulceration or gastroesophageal reflux disease.
- Patients with unresolved toxicities of grade 2 or more from prior anti-cancer therapies.
- Untreated or symptomatic central nervous system metastases. Patients with a history of brain metastases are eligible if definitive therapy has been administered (surgery and/or radiation therapy), there is no planned treatment for brain metastases, and the patient is clinically stable and is off corticosteroids for at least 2 weeks prior to enrolment.
- Major surgical procedures within 28 days prior to enrolment.
- Clinically significant cardiovascular diseases that are symptomatic or uncontrolled.
- Known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen.
- Pregnant or breast-feeding females.
- Patients who have hearing impairment, due to the potential for ototoxicity of cisplatin.
- Any history or presence of clinically significant cardiovascular, respiratory, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease or any other condition which in the opinion of the Investigator could jeopardize the safety of the patient or the validity of the study results
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的:Regimen A / Amended Regimen A
Regimen A: Cisplatin + 5-fluorouracil ASLAN001 daily in combination with: Cisplatin 80 mg/m2 IV infusion for 1 day and 5-fluorouracil 800 mg/m2/day IV infusion for 5 days every 3 weeks for up to 6 cycles. Or Amended Regimen A: Cisplatin + 5-fluorouracil + leucovorin ASLAN001 daily in combination with: Cisplatin 35 mg/m2 24-hour infusion for day 1 and day 8, 5-fluorouracil 2,000 mg/m2 and Leucovorin 300mg/m2 24-hour infusion for day 1, day 8 and day 15 every 4 weeks for up to 6 cycles. |
ASLAN001 400mg BID daily; ASLAN001 500mg BID daily; or ASLAN001 300mg BID daily
其他名称:
Cisplatin 80 mg/m2 IV infusion and 5-fluorouracil 800 mg/m2/day IV infusion for 5 days every 3 weeks; Or Cisplatin 35 mg/m2 24-hour infusion for day 1 and day 8, 5-fluorouracil 2,000 mg/m2 and Leucovorin 300mg/m2 24-hour infusion for day 1, day 8 and day 15 every 4 weeks. |
|
实验性的:Regimen B
Regimen B: Cisplatin + capecitabine ASLAN001 daily in combination with: Cisplatin 60-80 mg/m2 IV infusion on Day 1 and capecitabine 1,000 mg/m2 orally BID for 14 days every 3 weeks for up to 6 cycles. |
ASLAN001 400mg BID daily; ASLAN001 500mg BID daily; or ASLAN001 300mg BID daily
其他名称:
Cisplatin 80 mg/m2 IV infusion and capecitabine 1,000 mg/m2 orally BID for 14 days every 3 weeks
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Safety and Tolerability of ASALN001
大体时间:First 2 cycles
|
Safety and tolerability as evaluated with: DLTs (in first 2 cycles); Maximum tolerated dose (MTD) of ASLAN001 in combination with cisplatin/capecitabine or cisplatin/5-FU will be determined. |
First 2 cycles
|
|
Safety and Tolerability of ASALN001
大体时间:Baseline to post-dose
|
Safety and tolerability as evaluated with: Adverse events. |
Baseline to post-dose
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Preliminary assessment of the efficacy
大体时间:Along the study duration
|
•To provide a preliminary assessment of the efficacy of ASLAN001 when given in combination in Regimen A or Regimen B as measured by the objective response rate (ORR).
|
Along the study duration
|
|
Pharmacokinetics profile (AUC) of ASLAN001
大体时间:Along the study duration
|
To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to area under the plasma concentration-time curve (AUC) from 0 to 6 hours (AUC0-6).
|
Along the study duration
|
|
Pharmacokinetics profile (Cmax) of ASLAN001
大体时间:Along the study duration
|
To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to maximum plasma concentration (Cmax).
|
Along the study duration
|
|
Pharmacokinetics profile (Cmin) of ASLAN001
大体时间:Along the study duration
|
To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to minimum (trough) plasma concentration (Cmin).
|
Along the study duration
|
|
Pharmacokinetics profile (RacAUC0-6) of ASLAN001
大体时间:Pharmacokinetic measurements will be from Cycle 1 Day 1 to Cycle 3 Day 1 (each cycle is 28 days for Amended Regimen A, and 21 days for Regimen A and B.
|
To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to accumulation ratio for AUC (RacAUC0-6).
|
Pharmacokinetic measurements will be from Cycle 1 Day 1 to Cycle 3 Day 1 (each cycle is 28 days for Amended Regimen A, and 21 days for Regimen A and B.
|
|
Pharmacokinetics profile (Tmax) of ASLAN001
大体时间:Along the study duration
|
To evaluate the pharmacokinetics of ASLAN001, when given in combination with
|
Along the study duration
|
合作者和调查者
调查人员
- 学习椅:ASLAN Pharma、ASLAN Pharmaceuticals
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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