A Phase 1 Study of an Oral p38 MAPK Inhibitor in Patients With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 89
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinically Significant Effects (Physical Assessments and Safety Lab Tests)
研究概览
简要总结
The objective of this study is to determine a safe dose of LY2228820 that may be given to participants with advanced cancer. Part A of this study will consist of dose escalation, and Part B will consist of dose confirmation.
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 (including lymphoma) that is advanced or metastatic disease for which no therapy of higher priority (approved therapies or therapies with published substantial evidence of effectiveness) is available, or for whom no standard therapy exists
- •Have the presence of measurable or nonmeasurable disease as defined by Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
- •Have adequate hematologic, renal, and hepatic organ function
- •Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
- •Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, or other investigational therapy for at least 14 days (42 days for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy
- •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 child bearing potential must have had a negative serum pregnancy test less than or equal to 7 days prior to the first dose of study drug
- •Have an estimated life expectancy of ≥ 12 weeks
- •Are able to swallow capsules and/or tablets
排除标准
- •Have received treatment within 14 days of the initial dose of study drug with a drug that has not received regulatory approval for any indication
- •Have a history of major surgical resection involving the stomach or small bowel, or have serious preexisting medical conditions (based on judgment of the investigator)
- •Have symptomatic central nervous system malignancy or metastasis (screening is not required)
- •Have a diagnosis of inflammatory bowel disease (Crohn's disease or ulcerative colitis)
- •Have an active hematologic malignancy other than lymphoma
- •Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb). Screening at baseline will not be required for enrollment
- •Concurrent administration of any immunosuppressive therapy
- •Females who are pregnant or lactating
- •Have received, within 7 days of the initial dose of study drug, either grapefruit juice or treatment with a drug that is a known inhibitor or inducer of Cytochrome P450 Enzyme 3A4 (CYP3A4). In addition, participants should not receive grapefruit juice or treatment with a CYP3A4 inhibitor or inducer during the study
研究组 & 干预措施
LY2228820
The study had 4 parts, dose-escalation (Part A), 2 dose-confirmation (Parts B and C), and a tumor-specific expansion for metastatic breast cancer (Part D).
Part A: Participants received escalating doses of 10, 20, 40, 65, 90, 120, 160, 200, 300, 420 and 560 milligrams (mg) of LY2228820 every 12 hours on Days 1 through 14 of a 28-day cycle.
Part B: Participants received 420 mg of LY2228820 every 12 hours Days 1 through 14 of a 28-day cycle. Participants received midazolam orally 2 days before the first dose and again after the morning dose of study drug on Day 8 during the first cycle of treatment.
Part C: Participants received 300 mg of LY2228820 every 12 hours Days 1 through 14 of a 28-day cycle.
Part D: Participants received 200 mg and 300 mg of LY2228820 in combination with tamoxifen.
干预措施: LY2228820 (Drug)
LY2228820
The study had 4 parts, dose-escalation (Part A), 2 dose-confirmation (Parts B and C), and a tumor-specific expansion for metastatic breast cancer (Part D).
Part A: Participants received escalating doses of 10, 20, 40, 65, 90, 120, 160, 200, 300, 420 and 560 milligrams (mg) of LY2228820 every 12 hours on Days 1 through 14 of a 28-day cycle.
Part B: Participants received 420 mg of LY2228820 every 12 hours Days 1 through 14 of a 28-day cycle. Participants received midazolam orally 2 days before the first dose and again after the morning dose of study drug on Day 8 during the first cycle of treatment.
Part C: Participants received 300 mg of LY2228820 every 12 hours Days 1 through 14 of a 28-day cycle.
Part D: Participants received 200 mg and 300 mg of LY2228820 in combination with tamoxifen.
干预措施: Midazolam (Drug)
LY2228820
The study had 4 parts, dose-escalation (Part A), 2 dose-confirmation (Parts B and C), and a tumor-specific expansion for metastatic breast cancer (Part D).
Part A: Participants received escalating doses of 10, 20, 40, 65, 90, 120, 160, 200, 300, 420 and 560 milligrams (mg) of LY2228820 every 12 hours on Days 1 through 14 of a 28-day cycle.
Part B: Participants received 420 mg of LY2228820 every 12 hours Days 1 through 14 of a 28-day cycle. Participants received midazolam orally 2 days before the first dose and again after the morning dose of study drug on Day 8 during the first cycle of treatment.
Part C: Participants received 300 mg of LY2228820 every 12 hours Days 1 through 14 of a 28-day cycle.
Part D: Participants received 200 mg and 300 mg of LY2228820 in combination with tamoxifen.
干预措施: Tamoxifen (Drug)
结局指标
主要结局
Number of Participants With Clinically Significant Effects (Physical Assessments and Safety Lab Tests)
时间窗: Baseline to study completion (Up to 41 months)
Data presented are the number of participants who experienced at least one treatment emergent adverse event (TEAE). A TEAE is defined as an event that first occurred or worsened after the administration of at least 1 dose of study drug, regardless of causality. A summary of serious AEs (SAEs) and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
次要结局
- Recommended Dose for Phase 2 Studies(Baseline to study completion (Up to 41 months))
- Percentage of Participants With Best Overall Response [Complete Response (CR)+Partial Response (PR)+Stable Disease (SD)](Baseline to study completion (Up to 41 months))
- PK: Area Under the Concentration-Time Curve From Time Zero to 8 Hours (AUC0-8) of LY2228820(Cycle 1, Days 1 and 14: predose, 0.5, 1, 2, 3, 4, 6 and 8 h postdose)
- PK: Maximum Plasma Concentration (Cmax) of LY2228820(Cycle 1, Days 1 and 14: predose, 0.5, 1, 2, 3, 4, 6 and 8 h postdose)
- Pharmacodynamics (PD): Number of Participants With Greater Than 50% Inhibition of p38 Mitogen-Activated Protein Kinase (MAPK) Activity on Day 1(Cycle 1 Day 1: predose, 1, 2, 4, and 6 h postdose)