A Phase 1, Multicenter, Open-Label Study of Oral Entrectinib (RXDX-101) in Adult Patients With Locally Advanced or Metastatic Cancer Confirmed to be Positive for NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 10
- 主要终点
- Dose-Limiting Toxicity (DLT)
研究概览
简要总结
Entrectinib (RXDX-101) is an orally available inhibitor of the tyrosine kinases TrkA (coded by the gene NTRK1), TrkB (coded by the gene NTRK2), TrkC (coded by the gene NTRK3), ROS1 (coded by the gene ROS1), and ALK (coded by the gene ALK). Molecular alterations to one or more of these targets are present in several different tumor types, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), prostate cancer, papillary thyroid cancer, pancreatic cancer, and neuroblastoma. Patients with locally advanced or metastatic cancer with a detectable molecular alteration in targets of interest may be eligible for enrollment.
Phase 1 will assess safety and tolerability of entrectinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and efficacy will be assessed in the dose expansion portion of the study.
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
- •Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors that have a NTRK1, NTRK2, NTRK3, ROS1, or ALK molecular alteration.
- •Measurable disease according to RECIST version 1.
- •Prior cancer therapy is allowed, including crizotinib, ceritinib, and investigational drugs.
- •Prior radiotherapy is allowed
- •Patients with controlled asymptomatic central nervous system involvement are allowed.
- •Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤
- •Adult patients age 18 years or older.
- •Life expectancy of at least 3 months.
排除标准
- •Current participation in another therapeutic clinical trial.
- •Prior treatment with entrectinib.
- •History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds).
- •History of additional risk factors for torsade de pointes (e.g., family history of long QT syndrome).
- •Known active infections (bacterial, fungal, viral including HIV positivity).
- •Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
- •Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis.
- •Peripheral neuropathy ≥ Grade 2.
研究组 & 干预措施
Entrectinib (RXDX-101)
Oral entrectinib (RXDX-101)
干预措施: Entrectinib (Drug)
结局指标
主要结局
Dose-Limiting Toxicity (DLT)
时间窗: 28 days following first dose of entrectinib
Determine dose-limiting toxicities of entrectinib.
Recommended Phase 2 Dose (RP2D)
时间窗: Approx. 6 months
Determine RP2D of entrectinib.
Overall Response Rate (ORR) in Dose Expansion
时间窗: Approx. 2 months
Per RECIST v1.1 as assessed by Investigator.
Maximum Tolerated Dose (MTD)
时间窗: 28 days following first dose of entrectinib
Determine MTD of entrectinib
次要结局
- Plasma Concentrations of Entrectinib(Cycle 1 Days 1, 7, 14, 28)
- Disease Control(Approx. 2 years)
- Duration of Response(Approx. 2 years)
- Overall Survival (OS)(Approx. 2 years)
- Progression-Free Survival (PFS)(Approx. 2 years)