NCT01779336暂停1 期
An Open Label Multicentre Phase 1 Study of Oral IGF-1R Inhibitor PL225B in Subjects With Advanced Refractory Solid Tumors.
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 70
- 试验地点
- 5
- 主要终点
- Maximum tolerated dose
研究概览
简要总结
Clinical study of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors. The primary objective is to determine the maximum tolerated dose and dose limiting toxicity (ies) of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors.
详细描述
An open label multicentre Phase 1 study of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors. This is a dose-finding trial using the modified Accelerated Titration Design with 3 new subjects per cohort and 100% dose increments in the accelerated phase followed by standard phase with 40% dose increments.Subjects will receive study drug on a daily basis for twenty-one (21) days according to the dose and schedule specified for a particular cohort of therapy. Toxicity profile of the drug will be assessed during Cycle 1 of subject treatment in each cohort for determination of Maximum Tolerated Dose (MTD) according to the schedule given below.
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 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects having histologically and/or cytologically confirmed non-haematological malignancy that is metastatic or unresectable and for which standard curative or palliative treatment does not exist or is no longer effective
- •Subjects should have measurable or evaluable disease
- •Subjects of either sex, of all races and ethnic groups, and ≥18 years of age
- •ECOG (Eastern Cooperative Oncology Group) performance status 0-1
- •Subjects with life expectancy of at least 4 months
- •Subjects with fasting plasma glucose ≤ 125 mg/dL and HbA1c < 6.5 % at screening Subjects with fasting plasma glucose ≤150 mg/dL and HbA1c ≤ 7.0 % at screening for the Diabetes Expansion Cohort.
- •For the Diabetes Expansion Cohort - Subjects with known history of type 2 diabetes mellitus that are well-controlled on a stable dose of oral anti-diabetic agents such as metformin and/or sulfonylureas for 4 weeks prior to screening.
- •Subjects must have normal organ and marrow function as defined below:
- •Absolute neutrophil count ≥ 1500/cmm
- •Platelets ≥ 100,000/cmm
- •Total bilirubinwithin normal limits of the institution
- •AST/ALT ≤ 2.5 X institutional upper limit of normal (ULN) or ≤ 5 X institutional upper limit of normal (ULN) in the presence of liver metastases
- •Creatinine ≤ 1.5 X institutional upper limit of normal (ULN)
- •Subjects willing for repeat oral dosing and follow-up, including pharmacokinetic sampling
- •Women of childbearing potential and men willing to agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the duration of study participation and for at least 4 weeks after withdrawal from the study, unless they are surgically sterilised
- •Ability to understand and the willingness to provide a written informed consent document
- •Exclusion Criteria
- •Subjects who have received any prior chemotherapy, radiotherapy, biologic/targeted anti-cancer therapy or surgery within 4 weeks (6 weeks for monoclonal antibodies, radioactive monoclonal antibodies or any radio- or toxin- immunoconjugates) before the first study drug administration and have not recovered (to AEs < Grade 2) from the toxic effects from any prior therapy
- •Subjects having received any other investigational agents within 4 weeks prior to the first study drug administration and have not recovered completely (to AEs < Grade 2) from the side effects of the earlier investigational agent
- •Subjects with documented history of diabetes mellitus except for the Diabetes Expansion Cohort
- •For the Diabetes Expansion Cohort - Subjects who have type 1 diabetes mellitus, maturity onset diabetes of the young, hyperglycemia due to reasons other than type 2 diabetes mellitus.
- •For the Diabetes Expansion Cohort - Subjects who currently require insulin, thiazolidinediones, dual proliferator-activated receptors (PPAR) agonists, glucagon-like peptide (GLP-1) analogues, dipeptidyl peptidase (DPP-IV) inhibitors or have received the same in the 4 weeks prior to screening.
- •Subjects with known complications of diabetes like diabetic nephropathy or diabetic retinopathy
- •Subjects with known brain metastases
- •Subjects with gastrointestinal abnormalities including inability to take oral medication, malabsorption or other conditions like chronic inflammatory bowel disease that may affect absorption.
- •Subjects with a history of myocardial infarction or uncontrolled cardiac dysfunction during the previous 6 months
- •Subjects with baseline QTc interval >470 msec at screening
- •Subjects on warfarin. Prophylactic anticoagulation with low molecular weight heparin is allowed
- •Subjects with history of anaphylaxis or angioedema, bronchial asthma, peptic ulcer and clinically significant food or drug allergy
- •Subjects with 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
- •Women who are pregnant or nursing
- •Subjects with known seropositivity to human immunodeficiency virus (HIV), positive for Hepatitis B, positive for Hepatitis C (antigen positive), or known hepatic cirrhosis
排除标准
- 未提供
研究组 & 干预措施
PL225B
Experimental
Patients will receive study drug on a daily basis until disease progression or unacceptable toxicity in sequential cohorts following accelerated titration design.
干预措施: PL225B (Drug)
结局指标
主要结局
Maximum tolerated dose
时间窗: End of Cycle 1 (i.e. 21 Days)
Subjects will receive study drug on a daily basis for twenty-one (21) days according to the dose and schedule specified for a particular cohort of therapy.Toxicity profile of the drug will be assessed during Cycle 1 of subject treatment in each cohort for determination of Maximum Tolerated Dose (MTD).
次要结局
- Activity of PL225B based on selected biomarkers(Until disease progression or unacceptable toxicity (expected to be 4-6 months))
- Objective response(Until disease progression or unacceptable toxicity (expected to be 4-6 months))
- Number of subject with adverse events(Until disease progression or unacceptable toxicity (expected to be 4-6 months))
- Pharmacokinetic profile(Cmax,Tmax and AUC)(Until disease progression or unacceptable toxicity (expected to be 4-6 months))
研究者
研究点 (5)
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