Phase 1 Study of a Notch Inhibitor in Patients With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinically Significant Effects
研究概览
简要总结
The objective of this phase 1 study is to evaluate the safety and tolerability of Notch Inhibitor in participants with advanced cancer. This study includes dose escalation and dose confirmation components.
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
- •The participants must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have ceased to provide clinical benefit for their disease.
- •The participants must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced and/or metastatic.
- •Have adequate organ function including:
- •Hematologic: Absolute neutrophil count (ANC) ≥1.5 x 10⁹/liter (L), platelets ≥100 x 10⁹/L, and hemoglobin ≥8 grams/deciliter (g/dL).
- •Hepatic: Bilirubin ≤1.5 times upper limits of normal (ULN) and alanine aminotransferase (ALT) ≤3.0 times ULN.
- •Renal: Serum creatinine ≤1.5 times ULN.
- •Have a performance status less than or equal to 1 for Dose Escalation and less than or equal to 2 for Dose Confirmation on the Eastern Cooperative Oncology Group (ECOG) scale.
- •Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (treatment-related toxicity resolved to baseline) except for residual alopecia.
- •Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug.
- •Females with childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of study drug.
排除标准
- •Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively.
- •Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, inflammatory bowel disease or history of major surgical resection involving the stomach or small bowel).
- •Have malabsorptive syndromes, enteropathies, gastroenteritis (acute or chronic), or diarrhea (acute or chronic).
- •Females who are pregnant or lactating.
- •Have Central Nervous System (CNS) malignancy or metastasis.
- •Have an acute leukemia.
- •Have active bacterial, fungal and/or known viral infection.
研究组 & 干预措施
LY900009
Dose escalation phase: 2 milligrams (mg), 4 mg, 8 mg, 15 mg, 30 mg, 45 mg and 60mg LY900009 administered orally 3 times per week (Monday, Wednesday, Friday) for 4 weeks of a 28-day cycle.
Dose confirmation phase: 30 mg LY900009 administered orally 3 times per week (Monday, Wednesday, Friday) for 4 weeks of a 28-day cycle.
Participants experiencing clinical benefit may continue treatment unless discontinuation criteria are met.
干预措施: LY900009 - Dose Escalation Phase (Part A) (Drug)
LY900009
Dose escalation phase: 2 milligrams (mg), 4 mg, 8 mg, 15 mg, 30 mg, 45 mg and 60mg LY900009 administered orally 3 times per week (Monday, Wednesday, Friday) for 4 weeks of a 28-day cycle.
Dose confirmation phase: 30 mg LY900009 administered orally 3 times per week (Monday, Wednesday, Friday) for 4 weeks of a 28-day cycle.
Participants experiencing clinical benefit may continue treatment unless discontinuation criteria are met.
干预措施: LY900009 - Dose Confirmation Phase (Part B) (Drug)
结局指标
主要结局
Number of Participants With Clinically Significant Effects
时间窗: Baseline to study completion up to 18.7 weeks
Clinically significant effects are study drug related serious adverse events (SAEs) and study drug related treatment emergent adverse events (TEAEs). A summary of all SAEs and all other non-SAEs regardless of causality is located in the Reported Adverse Events module.
次要结局
- Pharmacokinetics: Maximum Concentration (Cmax) of LY900009(Day1: Pre-dose, 0.5 hours (hr), 1 hr, 3-4 hr, 6-8 hr and 24-30 hours post-dose)
- Recommended Dose Range for Phase 2 Studies(Predose up to 28 days in Cycle 1)
- Percentage of Participants With a Best Overall Response of Stable Disease or Better (Document the Antitumor Activity)(Baseline to measured progressive disease up to 15.1 weeks)
- Pharmacokinetics: Area Under the Concentration-time Curve of LY900009 From Time Zero to Infinity [AUC(0-infinity)](Day1: Pre-dose, 0.5 hours (hr), 1 hr, 3-4 hr, 6-8 hr and 24-30 hours post-dose)