A Phase I, Dose-Escalation, Safety and Tolerability Study of COH29 in Patients With Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy Exists
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose of RNR inhibitor COH29, defined as the dose level with no more than 1 dose limiting toxicity (DLT) in the first 6 patients at a dose level below a dose level with DLT in 2 of 6 patients, graded according to CTCAE version 4.0
研究概览
简要总结
This phase I trial studies the side effects and best dose of RNR Inhibitor City of Hope 29 (COH29) in treating patients with solid tumors that are refractory to standard therapy or for which no standard therapy exists. COH29 may inhibit an enzyme called ribonucleotide reductase and may interfere with the ability of tumor cells to grow.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose of COH29 (ribonucleotide reductase [RNR] inhibitor COH29) and recommended dose for further phase II testing.
II. To determine the pharmacokinetics of COH29.
SECONDARY OBJECTIVES:
I. To characterize the safety and tolerability of COH29 by assessing toxicities per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
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
- •All patients must have the ability to understand and the willingness to sign a written informed consent
- •Life expectancy of greater than 3 months by physician assessment
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Patients must have histologically or cytologically confirmed (at original diagnosis or subsequent recurrence or progression) solid tumor that is metastatic, unresectable, progressive, or recurrent, and for which standard curative or palliative measures do not exist or are no longer effective
- •Patients must have measurable or evaluable disease
- •Patients must not have received prior chemotherapy or radiation for < 4 weeks prior to start of study treatment
- •Patients may be entered if they have received prior radiation therapy involving =< 30% of the bone marrow; any prior radiation therapy must have been administered >= 4 weeks prior to start of study treatment and the patient must be recovered from the acute toxic effects of the treatment prior to start of study treatment
- •Patients may be enrolled with a history of treated brain metastases that are clinically stable for >= 4 weeks prior to start of study treatment
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; women of child-bearing age will undergo urine pregnancy testing prior to study enrollment; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
- •Active breast-feeding is also not allowed on study enrollment
- •Leukocytes >= 3,000 cells/µL
- •Absolute neutrophil count >= 1,500 cells/µL
- •Platelets >= 100, 000 cells/µL
- •Total bilirubin =< 1.5 times the upper limit of normal (ULN)
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN; AST/ALT =< 5 x ULN if liver metastasis is present
- •Serum creatinine =< 1.5 mg/dL or a measured creatinine clearance >= 50 mL/min
- •Prothrombin time (PT)/international normalized ratio (INR)/ activated partial thromboplastin time (aPTT) =< 1.5 x ULN
- •Negative serum beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only)
排除标准
- •Patients may not be receiving any other investigational agents; use of over-the-counter herbal medications will also be excluded
- •Patients with uncontrolled undercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
- •Patients unable or unwilling to swallow pills
- •Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease or heart block, or uncontrolled congestive heart failure
- •Patients with a history of noninfectious pneumonitis will be excluded during the dose-escalation phase of the trial
- •Patients, who in the opinion of the investigator and another independent party, may not be able to adhere to the safety monitoring requirements of the study
研究组 & 干预措施
Treatment (RNR inhibitor COH29)
Patients receive RNR inhibitor COH29 PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (RNR inhibitor COH29)
Patients receive RNR inhibitor COH29 PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: RNR inhibitor COH29 (Drug)
Treatment (RNR inhibitor COH29)
Patients receive RNR inhibitor COH29 PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum tolerated dose of RNR inhibitor COH29, defined as the dose level with no more than 1 dose limiting toxicity (DLT) in the first 6 patients at a dose level below a dose level with DLT in 2 of 6 patients, graded according to CTCAE version 4.0
时间窗: Day 28
次要结局
- Changes in plasma biomarker expression levels(Baseline to up to 30 days after completion of study treatment)
- Pharmacokinetics of RNR inhibitor COH29(Pre-dose and 15 minutes, 30 minutes, 1, 2 , 3, 4, 6, 8, 24, and 168 hours post the day 1, course 1 dose)
- Toxicities according to the National Cancer Institute (NCI) CTCAE v 4.0(Up to 30 days after completion of study treatment)
- Response rate(Up to 30 days after completion of study treatment)
- RR protein levels as assessed by automated quantitative analysis (AQUA)(Baseline)