A Phase 1b Study of LY573636-sodium in Combination With Alimta (Pemetrexed) in Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 Dose
研究概览
简要总结
The primary objective of this study is to determine the maximum tolerated dose (MTD) regimen for the combination therapy of LY573636 and pemetrexed that may be safely administered to patients with a solid tumor that is not amenable to curative therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •You must have a diagnosis of a solid tumor malignancy that is not amenable to curative therapy
- •You must have a serum albumin level greater than or equal to 3.0 grams per deciliter (g/dL) [30 grams per liter (g/L)]
- •You must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- •You must be reliable and willing to make yourself available for the duration of the study and are willing to follow study procedures
- •Patients with reproductive potential should use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drugs
- •Your test results assessing the function of your blood, kidneys, liver, and heart are satisfactory
- •You must be willing to take folic acid, Vitamin B12, or prophylactic steroids
- •You must able to interrupt the use of aspirin (other than an aspirin dose less than or equal to 1.3 grams per day) and/or other nonsteroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents, such as piroxicam)
- •You must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, hormone therapy, or other investigational therapy for at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) before study enrollment and recovered from the acute effects of therapy (except alopecia). Patients who have received whole-brain radiation must wait 90 days before starting study therapy.
- •You must sign an informed consent
排除标准
- •You cannot have received other investigational drugs within the last 30 days
- •You cannot have other on-going serious illnesses including active bacterial, fugal, or viral infections
- •You cannot require regular, periodic paracentesis or thoracentesis
- •You cannot have active brain metastasis
- •You cannot currently be receiving warfarin (Coumadin®) therapy
- •You cannot be pregnant or lactating
- •You cannot have received prior pemetrexed or LY573636
- •You cannot have a second primary malignancy that could affect interpretation of the study results
研究组 & 干预措施
Experimental: Pemetrexed followed by LY573636
Pemetrexed on Day 1 followed by LY573636 on Day 4
干预措施: LY573636 (Drug)
Experimental: Pemetrexed followed by LY573636
Pemetrexed on Day 1 followed by LY573636 on Day 4
干预措施: Pemetrexed (Drug)
Experimental: LY573636 followed by Pemetrexed
LY573636 on Day 1, pemetrexed on Day 4
干预措施: LY573636 (Drug)
Experimental: LY573636 followed by Pemetrexed
LY573636 on Day 1, pemetrexed on Day 4
干预措施: Pemetrexed (Drug)
Experimental: LY573636 and Pemetrexed on Day 1
LY573636 and Pemetrexed on Day 1
干预措施: LY573636 (Drug)
Experimental: LY573636 and Pemetrexed on Day 1
LY573636 and Pemetrexed on Day 1
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Recommended Phase 2 Dose
时间窗: Baseline to toxicity [up to end of Cycle 1 (cycle = 21 or 28 days)]
Based on maximum tolerated dose (MTD) in Cycle 1: highest dose where \<33% participants (pts) had dose-limiting toxicity (DLT). DLTs were adverse events (AE) possibly related to study drug or AEs that met any of National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTAE): Grade (G) 4 neutropenia lasting ≥5 days; G4 neutropenia with fever, G4 thrombocytopenia, G3 thrombocytopenia with bleeding, ≥G3 non-hematologic toxicity (except nausea/vomiting and diarrhea controlled by medication; electrolyte toxicity resolved with standard replacement treatment; alopecia; and elevated alanine aminotransferase or aspartate aminotransferase with preexisting hepatic metastasis, if agreed by investigator). Investigators, with sponsor, could declare a DLT if pt experienced increasing toxicity during treatment and it was clear that further treatment would expose pt to excessive risk. Enrollment was stopped during the dose-escalation phase, thus further dose-escalation was not explored.
次要结局
- Number of Participants With Clinically Significant Effects(Baseline to end of study (up to 1 year of treatment plus 30-day follow-up))
- Percentage of Participants With a Tumor Response(Baseline to progressive disease (up to 1 year of treatment plus 30-day follow-up))
- Pharmacokinetics, Concentration Maximum (Cmax) of LY573636(Cycles 1 and 2 on Day 4 (prior to and at the end of LY573636 infusion, 2 and 4 hours post LY573636 infusion), Day 8 (anytime), Day 15 (anytime))
- Pharmacokinetics, Area Under the Curve (AUC) of LY573636(Cycles 1 and 2 on Day 4 (prior to and at the end of LY573636 infusion, 2 and 4 hours post LY573636 infusion), Day 8 (anytime), Day 15 (anytime))