A Phase 2, Open-Label, Multi-Center Study of Amuvatinib in Combination With Platinum-Etoposide Chemotherapy in Small Cell Lung Cancer Subjects Who Have Not Responded to Standard Treatment or Relapsed After Standard Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 12
- 主要终点
- Overall objective response rate (CR or PR)
研究概览
简要总结
The purpose of the study is to evaluate the safety and potential benefit of combination amuvatinib with standard of care chemotherapy treatment (platinum and etoposide) in small cell lung cancer (SCLC) subjects.
详细描述
Amuvatinib is an oral multi-targeted tyrosine kinase inhibitor which inhibits the mutant forms of c-Kit and PDGFR alpha. It also disrupts DNA repair likely through suppression of Homologous Recombination protein Rad51. In a Phase 1b clinical study in combination with VP-16 and carboplatin, responses in SCLC were observed. In vitro and in vivo data demonstrated amuvatinib synergy with VP-16 thereby further supporting this combination for continued evaluation in clinical trials. Pharmacokinetic data from Phase 1 clinical trials suggest that co-administration of amuvatinib did not alter exposures of standard of care agents VP-16 or carboplatin as measured by overall exposure.
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
- •Male or female ≥ 18 of age at the time of consent and have histologically or cytologically confirmed SCLC
- •Measurable SCLC per RECIST guideline that meets one of the following:
- •Disease progression by RECIST at anytime during platinum-etoposide (PE) chemotherapy;
- •Relapse by RECIST within 90 days after completing PE chemotherapy;
- •Stable disease by RECIST as best response after at least two (2) ≥ 21-day cycles of PE chemotherapy. The assessment of stable disease should be made at least 2 weeks after the start of the second cycle
- •Subjects who received another second-line therapy are eligible if they still fulfill any one of the above three conditions, and all other eligibility criteria
- •Start treatment with the same last regimen (dose and schedule) of first-line PE chemotherapy that they progressed or relapsed on, including any dose reductions because of toxicity, prior to study entry
- •ECOG performance status 0 to 2
- •Adequate organ function
- •Subjects with screening 12-lead ECG with measurable QTc interval of < 450 msec. If QTc ≥ 450 msec, then confirm the reading by evaluating the mean QTc interval of triplicate ECGs.
- •Sign approved informed consent form
排除标准
- •Prior exposure to amuvatinib
- •No longer eligible for first-line PE chemotherapy due to toxicity and the Investigator believes that the risk of retreating with the same PE chemotherapy regimen would outweigh the benefit
- •Ongoing toxicity from prior treatment unless the toxicity has resolved, or in the opinion of the Investigator, is stable and does not compromise the safety of the subject
- •Mixed SCLC and non-small cell lung cancer, or large cell lung cancer
- •Untreated, unstable, or symptomatic brain metastasis
- •Hypersensitivity to amuvatinib, excipients of amuvatinib, or any agent given in association with this trial
- •A life-threatening illness, medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety or interfere with study outcomes
研究组 & 干预措施
Amuvatinib
Amuvatinib 300 mg PO TID + standard-of-care platinum-etoposide
干预措施: Amuvatinib (Drug)
结局指标
主要结局
Overall objective response rate (CR or PR)
时间窗: 3 months
次要结局
- Disease control rate(6 months)
- Safety and tolerability(6 months)
- Progression-free survival and overall survival(6 months)
- Duration of response(6 months)
- Amuvatinib and metabolites PK and other biomarkers(6 months)
- Amuvatinib PK interactions with platinum-etoposide chemotherapy(6 months)