NCT02383368已完成1 期
An Open-Label, Dose-Escalation/Expansion Phase 1 Study of ASP4132 Given Orally to Patients With Advanced Refractory Solid Tumors and Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 5
- 主要终点
- Safety as assessed by electrocardiograms (ECG)
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of ASP4132 and to determine the maximum tolerated dose and recommended phase 2 dose of ASP4132. The study will also determine the pharmacokinetics (PK) of ASP4132 and evaluate the preliminary antitumor activity.
详细描述
The study consists of two parts and these will be conducted sequentially: Part 1 (dose escalation) and Part 2 (dose expansion). Subjects will participate in Part 1 or Part 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Subject has a life expectancy of more than 3 months
- •Subject agrees not to participate in another interventional study while on treatment.
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Female subject must be either:
- •Of non-child bearing potential:
- •post-menopausal (defined as at least 1 year without any menses) prior to Screening,
- •or, documented surgically sterile or status post hysterectomy
- •Or, if of childbearing potential,
- •agree not to try to become pregnant during the study and for 90 days after the final study drug administration;
- •if heterosexually active must use two forms of birth control
- •Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and continue throughout the study period and for 90 days after the final study drug administration.
- •Subject must have advanced and/or metastatic, histologically or cytologically documented cancer or lymphomas, for whom there is no available standard therapy shown to provide clinical benefit.
排除标准
- •Subject has absolute neutrophil count < 1000/μL, platelet count < 75,000/μL, and hemoglobin < 8 g/dL (< 5 mmol/L) at Screening
- •Subject has total serum bilirubin ≥1.5 times the upper limit of normal (ULN),serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) > 3 times ULN, or albumin ≤ 3.0 g/dL at Screening.
- •Subject has any abnormalities in serum sodium, potassium, chloride, calcium and magnesium levels ≥ Grade 2 at screening (CTCAE Version 4.03).
- •Subject has a known elevation in serum lactate at screening ˃ 2x institutional ULN
- •Subject has an estimated glomerular filtration rate (eGFr) of < 60ml/min as calculated by the modification of diet Renal disease (MDRD) Equation.
- •Subject with a QTcF of > 450 msec in male subjects and > 470 msec in female subjects on the screening 12 lead ECG.
- •Subject has Neuropathy ≥ Grade 2 at Screening.
- •Subject has Type 1 Diabetes Mellitus or Type 2 Diabetes Mellitus and currently being treated with insulin or sulfonylureas.
- •Subject has concomitant active second malignancies unless remission was achieved at least 3 years prior to study entry and subject is no longer on therapy for the malignancy.
- •Subject has a significant cardiovascular disease
- •Subject has a known history of acute or chronic hepatitis B (HBV), HIV or hepatitis C (HCV) infection.
- •Subject has serious/active bacterial, viral or fungal infection requiring systemic treatment.
- •Subject has significant gastrointestinal abnormalities, including ulcerative colitis, chronic diarrhea associated with intestinal malabsorption, Crohn's disease, and/or prior surgical procedures affecting absorption or requirement for intravenous (IV) alimentation.
- •Subject has active central nervous system (CNS) metastases not controlled by prior surgery or radiotherapy (subjects must be off steroids). Subjects with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by brain MRI/CT.
- •Subject has concurrent severe or uncontrolled medical disease or organ system dysfunction which, in the opinion of the Investigators, would limit life expectancy to < 3 months.
- •Subject has psychiatric disorder or altered mental status that would preclude an understanding of the informed consent process and/or completion of the necessary study procedures.
- •Subject has difficulty swallowing large pills.
- •Subject currently being treated with biguanides or other agents known to increase risk of lactic acidosis.
- •Subject has unavoidable concomitant treatment with any drug known for causing Torsades de Pointes.
- •Subject has had radiotherapy or surgery within the 4 weeks prior to treatment with ASP
- •Subject has not discontinued all previous systemic therapies for cancer including chemotherapy, immunotherapy, or biological therapies for at least 14 days prior to the initiation of ASP
- •Subject has not fully recovered from the acute toxicities (except alopecia) of any prior anti-cancer therapy.
- •Subject requiring concomitant use of strong CYP3A4 inhibitors or inducers.
研究组 & 干预措施
ASP4132 dose escalation
Experimental
Subjects will receive a single dose of the study drug on Day -4 (Single-Dose Period), followed by PK sampling prior to Multiple-Dose Period where they will receive the same dose as they received in the Single-Dose Period on one of four schedules:
Continuous - daily dosing for 28 days, Intermittent: Schedule A: 3 days on / 4 days off; Schedule B: 1 days on / 6 days off; Schedule C: 3 days on / 11 days off.
干预措施: ASP4132 (Drug)
ASP4132 dose expansion
Experimental
Subjects in Part 2 will be treated with ASP4132 at the MTD and dosing schedule identified from Part 1.
干预措施: ASP4132 (Drug)
结局指标
主要结局
Safety as assessed by electrocardiograms (ECG)
时间窗: up to 39 months
Safety as assessed by adverse events
时间窗: up to 39 months
Safety as assessed by clinical laboratory tests
时间窗: up to 39 months
Safety as assessed by vital signs
时间窗: up to 39 months
次要结局
- Objective response rate to ASP4132(Week 16)
- Duration of response to ASP4132(Week 16)
- Disease control rate to ASP4132(Week 16)
- Maximum concentration (Cmax) of ASP4132(up to 43 days)
- Time of the maximum concentration (Tmax) of ASP4132(up to 43 days)
- Area under the concentration-time curve from time of dosing to the last measurable concentration (AUClast) of ASP4132(up to 43 days)
- AUC from the time of dosing to 24 hours (AUC24) of ASP4132(up to 43 days)
- AUC from the time of dosing extrapolated to time infinity (AUCinf) of ASP4132(up to 43 days)
- Apparent terminal elimination half-life (T1/2) of ASP4132(up to 43 days)
- Accumulation ratio of ASP4132(up to 43 days)
- Apparent total systemic clearance after single or multiple extravascular dosing (CL/F) of ASP4132(up to 43 days)
- Apparent volume of distribution during the terminal elimination phase after single or multiple extravascular dosing (Vz/F) of ASP4132(up to 43 days)
- Progression-free survival(up to 39 months)
研究者
研究点 (5)
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