A Phase 1 Dose-escalation Study of Intermittent, Once Weekly, and Continuous Daily Oral OSI-027 Dosing in Patients With Advanced Solid Tumors or Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 128
- 试验地点
- 3
- 主要终点
- Maximum tolerated dose
研究概览
简要总结
The primary objective of this study is to determine the maximum tolerated dose (MTD) and to establish the recommended phase 2 dose of oral OSI-027 when administered via 3 schedules, namely, intermittent, weekly, and continuous in patients with advanced solid tumors or lymphoma, namely, intermittent, weekly, and continuous.
详细描述
The study will open with Schedule 1 (S1, intermittent) with initiation of Schedule 2 (S2, weekly) and Schedule 3 (S3, continuous), which may occur in parallel after observation of clinically significant related dose limiting toxicity (DLT) in the S1 schedule. Dosing will be initiated on Day 1 with intermittent weekly dosing continuing for 21 days (1 Treatment Period). Expansion of Dose Escalation Cohorts may occur for S1 and S2 at the recommended phase 2 dose level(s) and a Biomarker Expansion Cohort may be opened in S1 and/or S2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Histologically or cytologically documented malignancy (solid tumor or lymphoma)
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2
- •Predicted life expectancy of at least 3 months
- •Adequate hematopoietic and hepatic function, and normal renal function
- •Fasting glucose <7mmol/L at baseline
- •Left ventricular ejection fracture (LVEF) by Multiple gated acquisition scan (MUGA)≥ 60%
- •Practice effective contraceptive measures throughout study
- •Verbal and written informed consent
- •Prior therapy:
- •Chemotherapy, minimum of 3 weeks and recovered from any treatment-related toxicities (except for alopecia, and grade 1 neurotoxicity) prior to registration
- •Hormonal, discontinued prior to registration
- •Radiation, minimum of 21 days and recovered from toxic effects prior to registration
- •Surgery, provided wound healing has occurred
排除标准
- •History of significant cardiac disease unless well controlled
- •Discontinuation from prior therapy due to cardiac toxicity
- •Active or uncontrolled infections
- •Serious illness or medical condition that could interfere with study participation
- •History of any psychiatric condition that might impair understanding or compliance
- •Documented history of diabetes mellitus
- •Pregnant or breastfeeding females
- •Unstable symptomatic brain metastases, that require steroid or that have required radiation in the last 28 days
- •Chronic systemic steroid use for cancer related condition
- •History of allergic reactions
- •Patients with cataract who are expected to undergo surgery within 6 months of registration
- •Use of drugs causing QT interval prolongation within 14 days prior to dosing
- •Patients with clinically significant electrolyte imbalances
研究组 & 干预措施
Schedule 1
Once daily for 3 days every 7 days
干预措施: OSI-027 (Drug)
Schedule 2
Once weekly
干预措施: OSI-027 (Drug)
Schedule 3
Once daily
干预措施: OSI-027 (Drug)
结局指标
主要结局
Maximum tolerated dose
时间窗: 21 days
次要结局
- Safety profile of OSI-027(up to 5 years)
- Pharmacokinetic profile of OSI-027(up to 23 days)
- Preliminary pharmacodynamic relationship with OSI-027 systemic exposure(up to 23 days)
- Preliminary antitumor activity of OSI-027(up to 5 years)