A Phase 1/1b, Multicenter, Open-Label Study of Intravenous RXDX-107 in Adult Patients With Locally Advanced or Metastatic Solid Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 70
- 试验地点
- 3
- 主要终点
- Phase 1: Plasma clearance (CL)
研究概览
简要总结
This is an open-label, Phase I/Ib, dose escalation study of intravenous RXDX-107 administered to subjects with advanced solid tumors. The study is designed to explore the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary clinical activity of RXDX-107 and to define a recommended Phase 2 dose (RP2D)
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
- •Confirmed relapsed or refractory locally advanced or metastatic solid cancer for whom no standard therapy is considered appropriate, or for whom standard therapy is considered intolerable.
- •>18 years of age.
- •ECOG performance status of 0 or
- •Life expectancy of at least 3 months.
- •Received the last dose of previous treatment / therapy before Day 1 of cycle 1:
- •28 days for cytotoxic chemotherapy, immunotherapy, whole brain radiotherapy, anticonvulsive therapy, stereotactic radiosurgery and major surgery
- •42 days for nitrosureas, mitomycin C, and liposomal anthracycline
- •14 days for non-cytotoxic cancer therapies and radiotherapy
- •Recovered from all toxic effects (excluding alopecia) of any prior anti-cancer therapy to Grade ≤ 1 or to the baseline laboratory values.
- •Adequate organ function and baseline laboratory values
- •Women of childbearing potential must have a negative serum pregnancy
- •Phase 1b: Patient must have measurable disease
排除标准
- •Receiving other experimental therapy
- •Known symptomatic brain mets or leptomeningeal involvement
- •Myocardial infarction in the previous 12 weeks. Active ischemia or any other uncontrolled cardiac condition such as angina pectoris, significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, or CHF.
- •Another concurrent illness which would preclude study conduct and assessment, uncontrolled: medical condition, active infection, risk of bleeding, diabetes mellitus, or pulmonary disease, or alcoholic liver disease, or primary biliary cirrhosis.
- •Malignancy within 3 years or active disease requiring treatment other than the target cancer. The exceptions are prostate cancer (Gleason grade < 6 with normalized PSA levels), treated in situ cervical, breast carcinoma, squamous or basal cell skin cancer.
- •Any condition that may compromise the ability to give written informed consent or to comply with the study protocol.
研究组 & 干预措施
RXDX-107
干预措施: RXDX-107 (Drug)
结局指标
主要结局
Phase 1: Plasma clearance (CL)
时间窗: Approx. 1 year
Plasma concentrations obtained following the dose on Day 1 (and from the dose on Day 2 in patients receiving the Day 1 and Day 2 schedule)
Phase 1: Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
时间窗: Approx. 6 months
Phase 1: Safety profile of RXDX-107 as characterized by Adverse Events, ECG and laboratory abnormalities
时间窗: Approx. 1 year
AEs, ECG and Labs assessed according to NCI CTCAE V4.0
Phase 1b: Confirm RP2D
时间窗: Approx. 1 year
Number of participants with Treatment-related AEs, Labs changes from baseline, and QTc interval changes from baseline assessed according to NCI CTCAE V4.0, concomitant medication usage, including all supportive care provided, and preliminary anti-tumor activity per RECIST v1.1 as assessed by Investigator
Phase 1: Maximum observed plasma drug concentration (Cmax)
时间窗: Approx. 1 year
Plasma concentrations obtained following the dose on Day 1 (and from the dose on Day 2 in patients receiving the Day 1 and Day 2 schedule)
Phase 1: Time to Cmax, by inspection (tmax)
时间窗: Approx. 1 year
Plasma concentrations obtained following the dose on Day 1 (and from the dose on Day 2 in patients receiving the Day 1 and Day 2 schedule)
Phase 1: Apparent plasma terminal elimination rate constant (λz) and associated terminal half life (t½)
时间窗: Approx. 1 year
Plasma concentrations obtained following the dose on Day 1 (and from the dose on Day 2 in patients receiving the Day 1 and Day 2 schedule)
Phase 1: Area under the drug concentration by time curve (AUC)
时间窗: Approx. 1 year
From time 0 to the time of the last detectable plasma concentration (AUC0-t)
Phase 1: Volume of distribution (Vz)
时间窗: Approx. 1 year
Plasma concentrations obtained following the dose on Day 1 (and from the dose on Day 2 in patients receiving the Day 1 and Day 2 schedule)
次要结局
- Antitumor activity of RXDX-107 as measured by Objective Response Rate (ORR)(Approx. 1 year)