NCT03130790已完成2 期
A Two-Part Phase 2/ 3 Multicentre, Double-Blind, Randomized, Placebo Controlled Study of Varlitinib Plus mFOLFOX6 Verses Placebo Plus mFOLFOX6 In Subjects With HER1/ HER2 Co Expressing Advanced or Metastatic Gastric Cancer Without Prior Exposure to Systemic Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 3
- 主要终点
- Percentage change from baseline in tumor size at Week 12 - Phase 2 part
研究概览
简要总结
This protocol for Varlitinib is developed for the treatment of Gastric Cancer. Varlitinib (also known as ASLAN001) is a small-molecule, adenosine triphosphate competitive inhibitor of the tyrosine kinases - epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, and HER4. Varlitinib may be beneficial to subjects with cancer by simultaneous inhibition of these receptors. The purpose of this study is to determine the safety and efficacy of Varlitinib in combination with mFOLFOX6 for the treatment of Gastric Cancer. Treatment groups are Varlitinib+mFOLFOX6 and Placebo+mFOLFOX6.
详细描述
Phase 2 is planned to recruit approximately 50 or more eligible subjects in order to obtain data from 40 evaluable patients. Anticipated completion date in Dec 2018. Recruitment completed.
Phase 3 is planned to recruit 350 patients. Anticipated completion date in Dec 2022. Not yet recruiting.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Subject with HER-2 over expression at level of +++ determined by IHC or subject confirmed HER2 2+ by IHC with HER2 gene amplification confirmed by Fluorescence in situ hybridization (FISH) in the central lab.
- •Prior systemic anti-cancer treatment for inoperable locally advanced, recurrent, or metastatic adenocarcinoma of the stomach or GEJ. However, previous neo adjuvant chemotherapy is allowed if subject has progression of disease more than 6 months after neoadjuvant treatment.
- •Subjects have undergone major surgery within 28 days prior to randomization
- •Subject with brain lesion, known brain metastases (unless previously treated and well controlled for a period of at least 4weeks).
- •Subject with malabsorption syndrome, diseases significantly affecting gastrointestinal function, extensive resection of the stomach or small bowel, or difficulty in swallowing and retaining oral medications.
- •Subjects with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, New York heart Association class III or IV congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, diabetes, hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Subjects with any history of other malignancy unless in remission for more than 1 year. (Nonmelanoma skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary).
- •Female subjects who are pregnant or breast feeding.
- •Subjects who were previously treated with varlitinib.
- •Subjects who took other investigational drugs and/or used investigational medical devices or have undergone major surgery within 28 days before initiating varlitinib therapy.
- •Are currently on or have received anti-cancer therapy, radiation or local treatment within the past 28 days
- •Subject with unresolved or unstable serious toxicity (≥ CTCAE 4.03 Grade 2) from prior administration of another investigational drug and/or prior cancer treatment(excluding hair loss)
- •Subjects with a known history of human immunodeficiency virus (HIV), decompensated cirrhosis, hepatitis B infection with hepatitis B virus DNA exceeding 2000 IU/mL or hepatitis C (treatment naïve or after treatment without sustained virologic response).
- •Known history of drug addiction within the past 1 year.
- •Subjects who need continuous treatment with proton pump inhibitors during the study period.
- •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 subject or the validity of the study results.
研究组 & 干预措施
Varlititib+mFOLFOX6
Experimental
干预措施: Varlitinib (Drug)
Varlititib+mFOLFOX6
Experimental
干预措施: mFOLFOX6 (Drug)
Placebo+mFOLFOX6
Placebo Comparator
干预措施: Placebo (Drug)
Placebo+mFOLFOX6
Placebo Comparator
干预措施: mFOLFOX6 (Drug)
结局指标
主要结局
Percentage change from baseline in tumor size at Week 12 - Phase 2 part
时间窗: At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 3 months)
Phase 2 part: Percentage change in tumour size defined as the percentage change from baseline in the sum of longest diameters of target lesions as assessed by ICR and defined by the RECIST v1.1 criteria
Overall Survival (OS) - Phase 3 part
时间窗: When 247 OS events have occured. 247 OS is estimated to occur after approximately 45 months
Phase 3 part: Overall Survival (OS) defined as the time from randomization until death by any cause. Any subject not known to have died at the time of the analysis will be censored based on the last recorded date on which the subject was known to be alive.
次要结局
- Pharmacokinetic: accumulation ratio for Cmax (Rac Cmax) - Phase 2 part(Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15)
- Progression-free survival (PFS) - Phase 3 part(When 247 Overall Survival (OS) events have occured (up to approximately 45 months))
- Time to response (TTR) - Phase 3 part(When 247 Overall Survival (OS) events have occured (up to approximately 45 months))
- Pharmacokinetic: maximum observed plasma concentration (Cmax) - Phase 2 part(Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15)
- Pharmacokinetic: accumulation ratio for AUC (Rac AUC0-6) - Phase 2 part(Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15)
- Progression-free survival (PFS) - Phase 2 part(At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 12 months))
- Overall Survival (OS) - Phase 2 part(From randomization to end of study (Last subject last visit (LSLV)) (up to approximately 24 months))
- Objective Response Rate (ORR) - Phase 3 part(When 247 Overall Survival (OS) events have occured (up to approximately 45 months))
- Health-related quality of life (QoL) - Phase 3 part(When 247 OS events have occured. 247 OS is estimated to occur after approximately 45 months)
- European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Gastric Cancer 22 items (EORTC QLQ STO22) measuring patients general cancer symptoms and functioning - Phase 3 part(When 247 OS events have occured. 247 OS is estimated to occur after approximately 45 months)
- Objective Response Rate (ORR) - Phase 2 part(At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 12 months))
- Time to response (TTR) - Phase 2 part(At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 12 months))
- Duration of Response (DoR) - Phase 2 part(At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 12 months))
- Disease Control Rate (DCR) - Phase 2 part(At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 12 months))
- Pharmacokinetic: area under the plasma concentration time curve (AUC) from 0 to 6 hours (AUC0-6) - Phase 2 part(Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15)
- Pharmacokinetic: time to Cmax (tmax) - Phase 2 part(Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15)
- Disease Control Rate (DCR) - Phase 3 part(When 247 Overall Survival (OS) events have occured (up to approximately 45 months))
- European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 items (EORTC QLQ-C30) measuring patients general cancer symptoms and functioning - Phase 3 part(When 247 OS events have occured. 247 OS is estimated to occur after approximately 45 months)
- Duration of Response (DoR) - Phase 3 part(When 247 Overall Survival (OS) events have occured (up to approximately 45 months))
- Incidence of Adverse Events (AEs) - Phase 3 part(When 247 Overall Survival (OS) events have occured (up to approximately 45 months))
研究者
研究点 (3)
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