A Phase 1 Dose-Escalation Study of LY2940680 in Patients With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 Dose: Maximum Tolerated Dose
研究概览
简要总结
The purpose of this study is to find a recommended dose level and schedule of dosing LY2940680 that can safely be taken by participants with advanced cancer. The study will also explore the changes in a cancer marker level in skin, hair follicles, buccal cells, and tumor cells. Finally, the study will help document any antitumor activity this drug may have.
详细描述
Participants may include those who have previously received treatment with another hedgehog smoothened (Hh/Smo) inhibitor (excluding LY2940680).
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
- •Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy.
- •Have the presence of measurable or nonmeasurable disease
- •Have adequate organ function, including:
- •Hematologic: Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, platelets greater than or equal to 100 x 109/L, and hemoglobin greater than or equal to 9 g/dL. Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin until 5 days after the erythrocyte transfusion.
- •Hepatic: Bilirubin less than or equal to 1.5 times upper limits of normal (ULN), ALT, and aspartate transferase (AST) less than or equal to 2.0 times ULN. If the liver has tumor involvement AST and ALT equaling less than or equal to 5 times ULN are acceptable.
- •Renal: Serum creatinine less than or equal to 1.5 times ULN.
- •Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- •Have discontinued previous treatments for cancer and recovered from the acute effects of therapy (for example, at least 42 days for mitomycin-C or nitrosoureas, 28 days for other chemotherapy and biologics. At the discretion of the investigator, hormone refractory prostate cancer patients who are stable on gonadotropin-releasing hormone (GnRH) agonist therapy and breast cancer patients who are stable on antiestrogen therapy (for example, an aromatase inhibitor) may continue treatment
排除标准
- •Have received treatment within 21 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication.
- •Have serious preexisting medical conditions
- •Have symptomatic central nervous system (CNS) malignancy (with the exception of medulloblastoma) or metastasis (screening not required). Patients with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 60 days.
- •Have known current hematologic malignancies or acute or chronic leukemia
- •Have a known active fungal, bacterial, and/or known viral infection including human immunodeficiency (HIV) or viral (A, B, or C) hepatitis (screening is not required)
- •Have a second primary malignancy that in the judgment of the investigator and sponsor may affect the interpretation of results
- •Have QTc interval of >500 msec on screening electrocardiogram
- •Patients who have previously received treatment with LY2940680
研究组 & 干预措施
Taladegib
Part A Cohort 1: 50 milligram (mg) taladegib administered orally QD on a 28-day cycle.
Part A Cohort 2: 100 mg taladegib administered orally QD on a 28-day cycle.
Part A Cohort 3: 200 mg taladegib administered orally QD on a 28-day cycle.
Part A Cohort 4: 400 mg taladegib administered orally QD on a 28-day cycle.
Part A Cohort 5: 600 mg taladegib administered orally QD on a 28-day cycle.
Part C: 400 mg taladegib administered orally QD. Participants with advanced solid tumors.
Part D: 400 mg taladegib administered orally QD. Participants with advanced basal cell carcinoma (BCC).
干预措施: Taladegib (Drug)
结局指标
主要结局
Recommended Phase 2 Dose: Maximum Tolerated Dose
时间窗: Time to First Dose to the End of Cycle 1 of Part A (Up To 28 Days)
Recommended Phase 2 dose was determined by maximum tolerated dose (MTD), which was determined by Dose-limiting toxicity (DLT). For the purpose of this study, the MTD was defined as the highest tested dose that had \<33% probability of causing a DLT in Cycle 1 of Part A.
次要结局
- PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556(Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h)
- PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556(Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h)
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞])(Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h)
- PK: Time of Maximal Concentration (Tmax)(Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h)
- PK: Maximum Observed Drug Concentration (Cmax)(Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h)
- Part C and D: Progression Free Survival (PFS)(Baseline to Progressive Disease or Death from Any Cause (Up To 32 Months))
- PK: Time of Maximal Concentration (Tmax) of LSN3185556(Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h)
- Number of Participants With Clinical Benefit Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR])(Baseline to Disease Progression or Death Due to Any Cause (Up To 32 Months))