A Phase 1 Multicenter, Dose-escalation Study of LY573636-sodium in Combination With 1) Gemcitabine HCl or 2) Docetaxel or 3) Temozolomide or 4) Cisplatin, or 5) Erlotinib in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 234
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose-Limiting Toxicities Cycle 1
研究概览
简要总结
The purpose of this study is to determine a safe dose of LY573636 (tasisulam) when used in 5 separate combinations with an approved cancer medication for treating participants with advanced cancer. Data from this study will be reviewed for any side effects or anti-tumor activity that may be associated with the LY573636 combination treatments.
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
- •Participants who have histologically confirmed solid malignancy or lymphoma that is unresectable and/or metastatic for which monotherapy with gemcitabine HCl, docetaxel, temozolomide, cisplatin, or erlotinib would otherwise be appropriate
- •Must have tumor progression after receiving standard/approved chemotherapy or limited treatment options
- •Must have measurable or nonmeasurable disease
- •Have given written informed consent prior to any study-specific procedures
- •Must have adequate hepatic, hematologic and renal function
- •Must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy or other investigational therapy for at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy. Endocrine therapies for the treatment of prostate cancer may be continued, at the discretion of the investigator. Whole brain radiation must have been completed 90 days before starting study therapy. Participants without evidence of brain metastases who have received prophylactic whole brain irradiation as part of standard of care for small cell lung cancer may be included in the study with a shorter washout period pending approval by the Lilly physician.
- •Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug.
- •Females with child-bearing potential must have had a negative serum pregnancy test within 7 days prior to the first dose of study drug.
- •Must have a serum albumin level greater than or equal to 3.0 g/dL (30 g/L).
- •Must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
排除标准
- •Have received treatment within 30 days of the initial dose of study drug with a drug that has not received regulatory approval for any indication
- •Have serious preexisting medical conditions that in the opinion of the investigator would preclude participation in the study
- •Participants with active central nervous system or brain metastasis at the time of study entry. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before study entry to rule out brain metastasis. Participants with stable CNS metastasis not requiring steroids may be eligible.
- •Have a current hematologic malignancy (other than lymphoma)
- •Participants with serious concomitant disorders, including active bacterial, fungal, or viral infection, incompatible with the study)
- •Participants actively receiving warfarin (Coumadin®) therapy
- •Participants who have previously completed or withdrawn from any study investigating LY573636
- •Participants with a known hypersensitivity to one of the combination drugs cannot be enrolled to the treatment arm which includes that chemotherapeutic combination
- •Females who are pregnant or breast feeding
- •Have known positive test results of HIV, hepatitis B, or hepatitis C
- •Participants receiving amiodarone, quinidine, propofol, or clozapine.
- •Participants receiving treatment with strong or moderate inhibitors of CYP2C19, including proton-pump inhibitors (PPIs). Esomeprazole or pantoprazole are allowed if not administered 72 hours before or after LY573636 administration.
研究组 & 干预措施
Gemcitabine plus LY573636
干预措施: Gemcitabine (Drug)
Gemcitabine plus LY573636
干预措施: LY573636 (Drug)
Docetaxel plus LY573636
干预措施: Docetaxel (Drug)
Docetaxel plus LY573636
干预措施: LY573636 (Drug)
Temozolomide plus LY573636
干预措施: Temozolomide (Drug)
Temozolomide plus LY573636
干预措施: LY573636 (Drug)
Cisplatin plus LY573636
干预措施: Cisplatin (Drug)
Cisplatin plus LY573636
干预措施: LY573636 (Drug)
Erlotinib plus LY573636
干预措施: Erlotinib (Drug)
Erlotinib plus LY573636
干预措施: LY573636 (Drug)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicities Cycle 1
时间窗: Baseline to Cycle 1 (Up to Day 28)
A Dose-Limiting Toxicity (DLT) is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria: Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) Grade 4 neutropenia lasting more than 5 days. Grade 4 neutropenia with fever or Grade 4 thrombocytopenia, regardless of duration; Grade ≥3 thrombocytopenia with bleeding, regardless of duration; Grade ≥3 nonhematologic toxicity (excluding nausea/vomiting or diarrhea that can be controlled with medication, and alopecia). Grade 3 electrolyte toxicity (for example, hypokalemia, hypophosphatemia) will not be considered a DLT unless it is considered related to the study drug or combination and does not resolve with standard replacement treatments within 42 days after Cycle 1 Day 1. A summary of other nonserious AEs and all Serious Adverse Events (SAE), regardless of causality is located in the Reported Adverse Event section.
次要结局
- PK: Area Under the Curve Albumin (AUCalb)(Cycle 1: predose,0,30min,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.)
- Pharmacokinetic (PK): Concentration Maximum (Cmax)(Cycle 1: predose,0,30min,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.)
- Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response)(Baseline to Study Completion (Up to 2 years))
- Number of Participants With a Clinically Significant Effects(Baseline to Study Completion (Up to 2 years))