A Phase 1 Study to Evaluate the Safety and Pharmacokinetic Profile of Icotinib in Patients With Advanced Cancers
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- MTD of icotinib hydrochloride, defined as the highest dose level at which =< 1 of 6 evaluable patients experiences a dose-limiting toxicity, as graded using NCI CTCAE version 4.0
研究概览
简要总结
This phase I trial studies the side effects and best dose of icotinib hydrochloride in treating patients with advanced cancers. Icotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the pharmacokinetic (PK) profiles of icotinib (icotinib hydrochloride) in patients with advanced cancers.
II. To determine the safety, tolerability and maximum tolerated dose (MTD) of icotinib in patients with advanced cancers.
SECONDARY OBJECTIVES:
I. To preliminarily assess the anti-tumor activity of icotinib in patients with advanced cancers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- •Histologically or cytologically confirmed locally advanced, inoperable or metastatic solid tumor
- •Have received at least one standard therapy for metastatic disease or have a disease in which no standard therapies exist
- •Platelet count >= 100 x 10^9/L
- •Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- •Hemoglobin (Hgb) >= 9 gm/dL
- •Total bilirubin =< 1.5 x upper limit of normal (ULN)
- •Alanine transaminase (ALT) and aspartate transaminase (AST) =< 3 x ULN (=< 5 x ULN if liver metastasis is present)
- •Creatinine clearance >= 40 mL/min; use the Cockroft and Gault formula
- •QTcB is < 480 msec
- •International normalized ratio (INR) =< 1.5
- •Activated partial thromboplastin time (APTT) =< 1.5 x ULN if not on anticoagulants; patients who are receiving therapeutic anticoagulation with heparin are allowed to participate provided that no prior evidence of underlying abnormality exists in these parameters; patients on warfarin should have stable doses with INR between 2-3 in the 2 months prior to study registration
- •Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
- •Demonstrate the ability to swallow and retain oral medication
- •Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of study drug
- •Male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received
- •Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
- •Written informed consent granted prior to initiation of any study-specific screening procedures, given with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
排除标准
- •Previous anti-cancer chemotherapy, immunotherapy or investigational agents =< 4 weeks prior to the first day of study defined treatment; palliative radiation =< 2 weeks; patients who receive gamma knife radiosurgery for brain metastases are eligible if procedure was performed >= 7 days before treatment is started; ongoing hormonal therapies (luteinizing hormone-releasing hormone [LHRH] antagonists, megestrol, octreotide, calcitonin, etc.) are allowed
- •History of cardiac disease: congestive heart failure defined as class II to class IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); previously diagnosed bradycardia or other cardiac arrhythmia defined as >= grade 2 according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0), or uncontrolled hypertension; myocardial infarction occurred within 6 months prior to study entry (myocardial infarction occurred > 6 months prior to study entry is permitted)
- •Active clinically serious infections defined as >= grade 2 according to NCI CTCAE version 4.0
- •Substance abuse, medical, psychological or social conditions that may, in the opinion of the investigator, interfere with the patient's participation in the study or evaluation of the study results
- •Any condition that is unstable or which could jeopardize the safety of the patient and his/her protocol compliance
- •Known human immunodeficiency virus (HIV) infection
- •Pregnancy or breast-feeding
- •Significant gastrointestinal disorder, in the opinion of the investigator, could interfere with the absorption of icotinib (e.g., significant, uncontrolled inflammatory bowel disease, history of abdominal fistula or gastrointestinal [GI] perforation within 6 months, extensive small bowel resection and requirement for tube feeding or parenteral hydration/nutrition)
- •Concomitant use of strong inhibitors or inducers of cytochrome P450 2C19 (CYP2C19) and CYP3A4 should be avoided
- •Untreated, symptomatic or unstable brain metastases
- •Major surgery < 4 weeks or minor surgery (e.g., talc pleurodesis, excisional biopsy, etc) < 2 weeks prior to the first day of study defined treatment
- •Unwilling or unable to follow protocol requirements
- •Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive study drug
研究组 & 干预措施
Treatment (icotinib hydrochloride)
Patients receive icotinib hydrochloride PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: icotinib hydrochloride (Drug)
Treatment (icotinib hydrochloride)
Patients receive icotinib hydrochloride PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (icotinib hydrochloride)
Patients receive icotinib hydrochloride PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
MTD of icotinib hydrochloride, defined as the highest dose level at which =< 1 of 6 evaluable patients experiences a dose-limiting toxicity, as graded using NCI CTCAE version 4.0
时间窗: 28 days
Overall toxicity incidence as well as toxicity profiles by dose level, subject and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
PK parameters of icotinib hydrochloride
时间窗: Cycle 1 only: Day -9 or Day -8: pre-dose, 0.5, 1, 2, 4, 6, 8, 24, and 48 hours; Day 8: pre-dose, 0.5, 1, 2, 4, 6, 8, and 24 (Day 9 pre-dose) hours; Day 15: pre-dose trough
Parameters include time to maximum concentration (Tmax), maximum concentration (Cmax), drug clearance (CL), half life (T 1/2), area under curve (AUC)0-infinity (inf), and AUC0-last measurable concentration (t) for the dosing interval following single and multiple dose administration.
次要结局
- Objective tumor response, assessed using RECIST 1.1(Up to 30 days after last dose of study drug)
- Best response, defined to be the best objective status recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started)(Up to 30 days after last dose of study drug)
- Frequency of toxicities, graded according to NCI CTCAE version 4.0(Up to 30 days after last dose of study drug)