A Phase I Study to Assess the Safety, Pharmacokinetics, and Potential Effects of Amrubicin on the QT/QTc Interval in Cancer Patients With Advanced Solid Tumors.
研究概览
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
-
-
California
-
La Jolla、California、美国、92093
- University Of California San Diego
-
Santa Monica、California、美国、90403
- Sarcoma Oncology Center
-
-
Indiana
-
Indianapolis、Indiana、美国、46202
- Indiana University Cancer Pavilion
-
-
Kentucky
-
Louisville、Kentucky、美国、40202
- James Graham Brown Cancer Center
-
-
Maryland
-
Baltimore、Maryland、美国、21215
- Sinai Hospital of Baltimore- Alvin and Lois Lapidus Cancer Institute
-
-
New York
-
Bronx、New York、美国、10467
- Montefiore Medical Center
-
-
Texas
-
San Antonio、Texas、美国、78229
- UT Health Science Center at San Antonio- Cancer Therapy and Research Center
-
-
Utah
-
Salt Lake City、Utah、美国、84112
- Hunstman Cancer Institute
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
Patients meeting all of the following criteria will be considered for enrollment into the study:
- Males or females, aged 18-65 years;
- Histological or cytological diagnosis of solid malignancy for which no acceptable standard therapy exists or for which approved standard therapy has failed;
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
- Life expectancy greater than 3 months;
- Nonsmoker or not smoked or used tobacco products for at least 3 months before the screening visit and agree to abstain from smoking/using tobacco products throughout the formal study and until the End of Study visit;
- Capable of giving informed consent, has signed the informed consent form, and is willing to comply with scheduled visits, dose administration, and other study procedures;
- Women of childbearing potential may participate, providing they have a negative serum pregnancy test (β-HCG) at screening, and a negative urine pregnancy test prior to dosing on Day 1 of each cycle;
- Males and females of childbearing potential must agree to the use of at least 2 effective contraceptive methods until at least 28 days following the last dose of study drug;
- Serum potassium, magnesium and corrected calcium that is within institutional normal range at screening;
Adequate organ function including the following:
- Adequate bone marrow reserve: absolute neutrophil count (segmented and bands) (ANC) ≥1.5 x 109/L, platelet count ≥100 x 109/L, and hemoglobin ≥90 g/L,
- Hepatic: bilirubin ≤1.5 x the upper limit of normal (ULN), ALT and AST ≤2.0 x ULN,
- Renal: serum creatinine ≤1.5 x ULN or calculated creatinine clearance >80 mL/min.
Exclusion Criteria:
Patients meeting any of the following criteria will be excluded from the study:
- Hypersensitivity to amrubicin or related compounds;
- Radiotherapy with curative intent to a primary disease complex ≤ 28 days before first dose; cranial radiotherapy ≤ 21 days before first dose; radiotherapy to all other areas ≤ 7 days before first dose of amrubicin;
- History or presence of clinically significant abnormal 12-lead ECG or triplicate ECGs with a mean QT interval corrected for heart rate (HR) using Fridericia's method (QTcF) of >450 msec (males) or >470 msec (females), a PR interval >240 msec or a QRS interval >110 msec (within 3 months of screening visit);
- Left ventricular ejection fraction (LVEF) <50%;
- Recent history (within 3 months of screening visit) of pericarditis and pericardial effusion;
History within 6 months of the screening visit of one of the following:
- cardiac disease including congenital long-QT syndrome,
- angina, congestive heart failure,
- myocardial ischemia or infarction,
- myocarditis, chest pain or dyspnea on exertion of cardiac origin,,
- idiopathic or hypertrophic cardiomyopathy,
- sarcoidosis,
- syncope,
- epilepsy,
- or other clinically significant cardiac disease;
- Family history of long QT syndrome;
- Use of implantable pacemaker or implantable cardioverter defibrillator;
- Clinically significant bradycardia (<50 beats per minute);
- Systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg;
- Previous treatment with an investigational agent or any anticancer therapy within 4 weeks prior to the 'off-drug' visit;
- Previous treatment with anticancer therapy and has not fully recovered (Common Terminology Criteria Adverse Event [CTCAE] Grade 1, except alopecia) from the toxic effects of that treatment;
- Treatment with any medication known to produce QT prolongation enzyme-inducing anticonvulsants, non-prescription medications including topical medications, all vitamins, minerals, herbs or dietary supplements/remedies (e.g., Saint John's Wort or Milk Thistle) for at least 7 days before the start of the off-drug visit;
- Previous treatment with any anthracycline;
- Any condition that would put the patient at undue risk or discomfort as a result of adherence to study procedures;
- Women who are pregnant or nursing;
- Uncontrolled intercurrent illness such as myelosuppression, renal impairment, hepatic impairment, infection and uncontrolled diabetes;
- Symptomatic central nervous system metastases. Patients with asymptomatic brain metastases are allowed. The patient must be stable for ≥ 2 weeks after radiotherapy, if the patient is on corticosteroids, the dose of corticosteroids must have been stable for ≥ 2 weeks prior to the first dose of study treatment, or be in the process of being tapered;
- Suspected, diffuse idiopathic interstitial lung disease or pulmonary fibrosis not related to prior treatment;
- History of seropositive HIV or patients who are receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications;
- Positive urine drug screen for undeclared concomitant medications and/or illegal drug use at screening.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:Amrubicin 40mg/m^2
Amrubicin 40mg/m^2 given as a 5 minute IV infusion on Days 1, 2 & 3 of a 21 day cycle
|
40mg/m^2 5 minute IV infusion for 3 consecutive days (21 day cycle)
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
To characterize the pharmacokinetics of amrubicin and amrubicinol (metabolite) in plasma, whole blood, and urine in patients given amrubicin as 5 minute IV infusions at 40 mg/m2 for 3 consecutive days; data will be obtained from blood & urine samples
大体时间:Cycle 1: all primary outcome measures are collected during the first 21 days.
|
The duration of making measurements during the first cycle is 21 days. All data relating to the primary outcome measure is collected during this time. There is an optional Extension Phase during which subjects can continue to receive additional 21-day cycles of amrubicin unless there is evidence of tumor progression or unacceptable toxicity. The duration of measurements depends on how long the subject continues on treatment. |
Cycle 1: all primary outcome measures are collected during the first 21 days.
|
To evaluate the potential effects on the QT/QTc interval in cancer patients when treated with 5 minute IV infusions of amrubicin 40 mg/m2 daily for 3 consecutive days; data will be obtained by ECG extraction from continuous 12-lead Holter monitoring
大体时间:Cycle 1: all primary outcome measures are collected during the first 21 days.
|
The duration of making measurements during the first cycle is 21 days. All data relating to the primary outcome measure is collected during this time. There is an optional Extension Phase during which subjects can continue to receive additional 21-day cycles of amrubicin unless there is evidence of tumor progression or unacceptable toxicity. The duration of measurements depends on how long the subject continues on treatment. |
Cycle 1: all primary outcome measures are collected during the first 21 days.
|
To determine the safety and tolerability of 40 mg/m2 amrubicin given as 5 minute IV infusions for 3 consecutive days; information will be collected by adverse event monitoring and laboratory safety tests.
大体时间:Cycle 1: all primary outcome measures are collected during the first 21 days.
|
The duration of making measurements during the first cycle is 21 days. All data relating to the primary outcome measure is collected during this time. There is an optional Extension Phase during which subjects can continue to receive additional 21-day cycles of amrubicin unless there is evidence of tumor progression or unacceptable toxicity. The duration of measurements depends on how long the subject continues on treatment. |
Cycle 1: all primary outcome measures are collected during the first 21 days.
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
1. Explore the relationship between pharmacokinetics and QTc interval change. Information will be obtained by further analysis of the datasets obtained from the primary outcome measures
大体时间:Cycle 1: all primary outcome measures are collected during the first 21 days.
|
The duration of making measurements during the first cycle is 21 days. All data relating to the primary outcome measure is collected during this time. There is an optional Extension Phase during which subjects can continue to receive additional 21-day cycles of amrubicin unless there is evidence of tumor progression or unacceptable toxicity. The duration of measurements depends on how long the subject continues on treatment. |
Cycle 1: all primary outcome measures are collected during the first 21 days.
|
合作者和调查者
赞助
调查人员
- 研究主任:Markus Renschler, MD、Celgene Corporation
出版物和有用的链接
一般刊物
- Chen N, et al. Phase I study to assess pharmacokinetics (PK), QT/QTc effect, and safety of amrubicin in patients (pts) with advanced solid tumors. Presented at 2011 ASCO Annual Meeting, June 3-7, 2011, Chicaco, IL. Abstract No. 7073 N
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
晚期实体瘤的临床试验
-
Advanced Bionics完全的重度至重度听力损失 | 在 Advanced Bionics HiResolution™ 仿生耳系统的成人用户中美国
-
AstraZeneca招聘中Adv Solid Malig - H&N SCC、ATM Pro / Def NSCLC、胃癌、乳腺癌和卵巢癌西班牙, 美国, 比利时, 英国, 法国, 匈牙利, 加拿大, 大韩民国, 澳大利亚
-
QIAGEN Gaithersburg, Inc完全的呼吸道合胞病毒感染 | 甲型流感 | 鼻病毒 | 乙型流感 | QIAGEN ResPlex II Advanced Panel | 人类副流感病毒 1 引起的感染 | 副流感 2 型 | 3 型副流感 | 副流感 4 型 | 人类偏肺病毒 A/B | 柯萨奇病毒/埃可病毒 | B/C/E 型腺病毒 | 冠状病毒亚型 229E | 冠状病毒亚型 NL63 | 冠状病毒亚型 OC43 | 冠状病毒亚型 HKU1 | 人类博卡病毒 | Artus 流感 A/B RT-PCR 检测美国