A Phase 1/Randomized Phase 2 Study to Evaluate LY2603618 in Combination With Gemcitabine in Patients With Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 157
- 试验地点
- 1
- 主要终点
- Phase 1: Determine the Recommended Phase 2 Dose for LY2603618 When Administered After Gemcitabine
研究概览
简要总结
The purpose of the Phase 1 portion of this study was to determine the dose of LY2603618 that can be safely administered 24 hours after gemcitabine treatment. This dose was then used for the Phase 2 portion of the study. The Phase 2 portion of the study evaluated whether LY2603618, when administered 24 hours after gemcitabine therapy, was an effective treatment for participants with pancreatic cancer.
详细描述
Phase 1 included a dose escalation of LY2603618 doses from 70 milligrams/meter squared (mg/m^2) to 250 mg/m^2 divided into 5 cohorts. Each participant was assigned to a single cohort with no intra-participant dose escalation. Phase 1 also included an expansion cohort where participants received a flat dose of 200 or 230 mg LY2603618. Participants received gemcitabine on Days 1, 8, and 15, followed by LY2603618 on Days 2, 9, and 16 of each 28-day cycle. The purpose of the Phase 1 portion was to determine the maximum tolerated LY2603618 dose to be carried into the Phase 2 portion of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with cancer that is metastatic and/or advanced during Phase 1
- •Diagnosed with pancreatic cancer that is metastatic and not amenable to surgery
- •Must be at least 18 years of age
- •Adequate hematological, liver, and renal functions
- •Eastern Cooperative Oncology Group (ECOG) status of 0 to 2
排除标准
- •Known hypersensitivity to gemcitabine
- •Pregnant or lactating females or refusal to use medically approved contraceptive precautions
- •Had prior treatment with radiotherapy involving more than 25% of marrow producing area
- •Have received treatment in the last 30 days with a drug which has not received regulatory approval for any indication at the time of study entry
研究组 & 干预措施
LY2603618 + Gemcitabine
Participants participated in Phase 1 or 2.
LY2603618 (Phase 1): 70 to 250 milligrams/meter squared (mg/m^2) LY2603618 as a 1-hour continuous intravenous (IV) infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression (DP). Participants received LY2603618 as part of the dose escalation cohort (dose of 70, 105, 150, 200, or 250 mg/m^2) or the expansion cohort (flat dose of 200 mg or 230 mg).
LY2603618 (Phase 2): 230 mg LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until DP.
Gemcitabine (Phase 1 and 2): 1000 mg/m^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until DP. Participants received gemcitabine 24 hours prior to LY2603618 administration.
干预措施: LY2603618 (Drug)
LY2603618 + Gemcitabine
Participants participated in Phase 1 or 2.
LY2603618 (Phase 1): 70 to 250 milligrams/meter squared (mg/m^2) LY2603618 as a 1-hour continuous intravenous (IV) infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression (DP). Participants received LY2603618 as part of the dose escalation cohort (dose of 70, 105, 150, 200, or 250 mg/m^2) or the expansion cohort (flat dose of 200 mg or 230 mg).
LY2603618 (Phase 2): 230 mg LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until DP.
Gemcitabine (Phase 1 and 2): 1000 mg/m^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until DP. Participants received gemcitabine 24 hours prior to LY2603618 administration.
干预措施: Gemcitabine (Drug)
Gemcitabine
Participants participated in Phase 2 only.
Gemcitabine (Phase 2): 1000 mg/m^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Phase 1: Determine the Recommended Phase 2 Dose for LY2603618 When Administered After Gemcitabine
时间窗: Baseline through 18 months
The recommended Phase 2 dose for LY2603618 when administered approximately 24 hours after gemcitabine was based on the maximum tolerated dose and achievement of predefined LY2603618 plasma systemic exposures targets (area under the LY2603618 plasma concentration versus time curve from time zero to infinity \[AUC(0-inf)\] \>21,000 nanogram\*hour/milliliter \[ng\*h/mL\] and maximum LY2603618 plasma concentration \[Cmax\] \>2000 nanograms/milliliter \[ng/mL\]).
Phase 2: Overall Survival (OS)
时间窗: Phase 2: Baseline to date of death
Overall survival (OS) time is defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the cut-off date. OS was summarized using Kaplan-Meier estimates.
次要结局
- Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618(Phase 1: LY2603618 - Predose and 0, 1, 3, 6, 24, 48, and 72 hours after the end of infusion on C1 /D2, C1 /D16, and C2 /D2. Gemcitabine - Predose and 0, 10, 30, 60, and 120 minutes after the end of infusion on C1 /D1, C1 /D15, and C2 /D1.)
- Phase 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618(Phase 2: LY2603618 - Predose and 0, 1, 3, and 24 hours after the end of infusion on Days 2 and 16 of Cycle 1. Gemcitabine - Predose and 0, 10, 60, and 120 minutes after the end of infusion on Days 1 and 15 of Cycle 1.)
- Phase 2: Progression-free Survival (PFS)(Phase 2: Baseline to measured progressive disease or date of death from any cause)
- Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618(Phase 1: LY2603618 - Predose and 0, 1, 3, 6, 24, 48, and 72 hours after the end of infusion on C1 /D2, C1 /D16, and C2 /D2. Gemcitabine - Predose and 0, 10, 30, 60, and 120 minutes after the end of infusion on C1 /D1, C1 /D15, and C2 /D1.)
- Phase 2: Maximum Plasma Concentration (Cmax) of Gemcitabine, dFdU, and LY2603618(Phase 2: LY2603618 - Predose and 0, 1, 3, and 24 hours after the end of infusion on Days 2 and 16 of Cycle 1. Gemcitabine - Predose and 0, 10, 60, and 120 minutes after the end of infusion on Days 1 and 15 of Cycle 1.)
- Phase 2: Clinical Benefit Rate(Phase 2: Baseline to measured progressive disease or date of death from any cause)
- Phase 2: Duration of Response(Phase 2. Baseline to measured progressive disease or date of death from any cause)
- Phase 2: Electrocardiogram QTc Prolongation(Phase 2: Days 2 and 16 of Cycle 1)
- Phase 2: Overall Response Rate(Phase 2: Baseline to measured progressive disease or date of death from any cause)
- Phase 1: Electrocardiogram QTc Prolongation(Phase 1: Days 2 and 16 of Cycle 1)