A Phase 1 Study of LY2801653 in Patients With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 190
- 试验地点
- 7
- 主要终点
- Recommended dose for phase 2 studies: Maximum tolerated dose
研究概览
简要总结
Part A- The purpose of this study is to determine a safe dose of LY2801653 to be given to participants with advanced cancer and to determine any side effects that may be associated with LY2801653 in this participant population. Efficacy measures will be used to assess the activity of LY2801653.
Part B- The dose determined in Part A will be used along with efficacy measures to assess the activity of LY2801653 in participants with adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma (HNSCC), uveal melanoma with liver metastasis, and cholangiocarcinoma.
Part C - the objective of Part C is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with HNSCC when taken with standard doses of cetuximab Part D - the objective of Part D is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with cholangiocarcinoma when taken with a standard dose of cisplatin.
Part E - the objective of Part E is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with cholangiocarcinoma when taken with gemcitabine plus cisplatin.
Part F - the objective of Part F is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with gastric cancer when taken with ramucirumab.
详细描述
Parts C and D were added to the registration in November, 2013, per protocol amendment. Parts E and F were added to the registration in February, 2015, per protocol amendment.
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
- •Part A- Diagnosed with advanced and/or metastatic cancer during dose escalation
- •Part B- Diagnosed with adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver with metastasis, or cholangiocarcinoma
- •Part C - Diagnosed with head and neck squamous cell carcinoma and have received at least one prior platinum-based systemic therapy
- •Part D - Diagnosed with cholangiocarcinoma and have not received more than 1 prior systemic therapy
- •Part E - Diagnosed with cholangiocarcinoma, either intrahepatic or extrahepatic, that is unresectable, recurrent, or metastatic. Participants must not have received prior systemic front line therapy for metastatic or resectable disease (i.e. participants may have received adjuvant gemcitabine but have not yet received gemcitabine/cisplatin for recurrent metastatic disease). Participants must be, in the opinion of the investigator, an appropriate candidate for experimental therapy. Participants should be evaluated for the need to undergo biliary drainage by stent placement prior to study participation. Participants should have adequate biliary drainage with no unresolved biliary obstruction.
- •Part F - Histologically- or cytologically-confirmed gastric carcinoma, including gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma (participants with adenocarcinoma of the distal esophagus are eligible if the primary tumor involves the GEJ). Participants must be ramucirumab naïve. Participants must be, in the opinion of the investigator, an appropriate candidate for experimental therapy. human epidermal growth factor receptor 2 (HER2)/neu status should be documented, if known.
- •Must be at least 18 years of age
- •Adequate hematologic, renal, and liver functions
- •Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
- •Ability to swallow capsules, with the exception of head and neck squamous cell carcinoma participants who may have study drug crushed and administered through a feeding tube
排除标准
- •Have serious preexisting medical conditions that would preclude participation in the study
- •Have a chronic underlying infection
- •Have symptomatic central nervous system (CNS) malignancy or metastasis
- •Have current acute or chronic leukemia
- •Are pregnant or lactating
- •Have hepatocellular cancer, liver cirrhosis with a Child-Pugh stage of B or higher, or have received a liver transplant
- •Have a history of congestive heart failure with a New York Heart Association class greater than 2, unstable angina, recent myocardial infarction (within 6 months of study enrollment), transient ischemic attacks, stroke, or arterial or venous vascular disease
- •Have a QTc interval greater than 470 msec
- •For participants in Part B, C, D, E, and F, a tumor tissue sample is mandatory, when safe and feasible, for biomarker analysis
研究组 & 干预措施
LY2801653
This study consists of a dose escalation of LY2801653 (Part A) followed by dose confirmation cohorts in four tumor types (adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver metastasis, and cholangiocarcinoma) (Part B).
Part C consists of dose determination for LY2801653 in combination with cetuximab in participants with head and neck squamous cell carcinoma followed by an expansion cohort.
Part D consists of dose determination for LY2801653 in combination with cisplatin in participants with cholangiocarcinoma followed by an expansion cohort.
Part E consists of dose determination for LY2801653 in combination with gemcitabine and cisplatin.
Part F consists of dose determination for LY2801653 in combination with ramicirumab.
干预措施: LY2801653 (Drug)
LY2801653
This study consists of a dose escalation of LY2801653 (Part A) followed by dose confirmation cohorts in four tumor types (adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver metastasis, and cholangiocarcinoma) (Part B).
Part C consists of dose determination for LY2801653 in combination with cetuximab in participants with head and neck squamous cell carcinoma followed by an expansion cohort.
Part D consists of dose determination for LY2801653 in combination with cisplatin in participants with cholangiocarcinoma followed by an expansion cohort.
Part E consists of dose determination for LY2801653 in combination with gemcitabine and cisplatin.
Part F consists of dose determination for LY2801653 in combination with ramicirumab.
干预措施: Cetuximab (Drug)
LY2801653
This study consists of a dose escalation of LY2801653 (Part A) followed by dose confirmation cohorts in four tumor types (adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver metastasis, and cholangiocarcinoma) (Part B).
Part C consists of dose determination for LY2801653 in combination with cetuximab in participants with head and neck squamous cell carcinoma followed by an expansion cohort.
Part D consists of dose determination for LY2801653 in combination with cisplatin in participants with cholangiocarcinoma followed by an expansion cohort.
Part E consists of dose determination for LY2801653 in combination with gemcitabine and cisplatin.
Part F consists of dose determination for LY2801653 in combination with ramicirumab.
干预措施: Cisplatin (Drug)
LY2801653
This study consists of a dose escalation of LY2801653 (Part A) followed by dose confirmation cohorts in four tumor types (adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver metastasis, and cholangiocarcinoma) (Part B).
Part C consists of dose determination for LY2801653 in combination with cetuximab in participants with head and neck squamous cell carcinoma followed by an expansion cohort.
Part D consists of dose determination for LY2801653 in combination with cisplatin in participants with cholangiocarcinoma followed by an expansion cohort.
Part E consists of dose determination for LY2801653 in combination with gemcitabine and cisplatin.
Part F consists of dose determination for LY2801653 in combination with ramicirumab.
干预措施: Gemcitabine (Drug)
LY2801653
This study consists of a dose escalation of LY2801653 (Part A) followed by dose confirmation cohorts in four tumor types (adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver metastasis, and cholangiocarcinoma) (Part B).
Part C consists of dose determination for LY2801653 in combination with cetuximab in participants with head and neck squamous cell carcinoma followed by an expansion cohort.
Part D consists of dose determination for LY2801653 in combination with cisplatin in participants with cholangiocarcinoma followed by an expansion cohort.
Part E consists of dose determination for LY2801653 in combination with gemcitabine and cisplatin.
Part F consists of dose determination for LY2801653 in combination with ramicirumab.
干预措施: Ramucirumab (Drug)
结局指标
主要结局
Recommended dose for phase 2 studies: Maximum tolerated dose
时间窗: Baseline to study completion (estimated as 3 months)
次要结局
- Number of participants with tumor response(Part A: Baseline to study completion (estimated as 3 months))
- Progression free survival (PFS)(Parts B, C, D: Baseline to study completion (estimated as up to 6 months))
- Number of participants with clinically significant effects(Baseline to study completion (estimated as 3 months))
- Pharmacokinetics: Maximum plasma concentration (Cmax)(Cycle 1, Day 1; Cycle 2, Day 1)
- Clinical benefit rate (CBR)(Parts B, C, D: Baseline to study completion (estimated as 3 months))
- Duration of response(Parts B, C, D: Baseline to study completion (estimated as up to 6 months))
- Maximum tolerated dose (MTD) of LY2801653 in combination with cisplatin for phase 2 studies in cholangiocarcinoma(Baseline to study completion (estimated as 3 months))
- Pharmacokinetics: Area under the concentration/time curve (AUC)(Cycle 1, Day 1; Cycle 2, Day 1)
- Maximum tolerated dose (MTD) of LY2801653 in combination with cetuximab for phase 2 studies in HNSCC(Baseline to study completion (estimated as 3 months))
- Maximum tolerated dose (MTD) of LY2801653 in combination with ramucirumab for phase 2 studies in gastric carcinoma(Baseline to study completion (estimated as 3 months))
- Maximum tolerated dose (MTD) of LY2801653 in combination with gemcitabine plus cisplatin for phase 2 studies in cholangiocarcinoma(Baseline to study completion (estimated as 3 months))