Study to Assess Pharmacokinetics, Immunogenicity and Safety/Tolerability of Patritumab (U3-1287)
2014年5月13日 更新者:Daiichi Sankyo, Inc.
Phase 1, Open-label Study Assessing the Pharmacokinetics, Immunogenicity and Safety/Tolerability of Process 2 Patritumab in Patients With Advanced, Refractory Solid Tumors
The purpose of this study is to assess the PK, safety, and tolerability of patritumab produced by a new manufacturing process (denoted as "Process 2 patritumab").
The data from this study will allow Process 2 patritumab to be compared to Process 1 patritumab to allow for any dose adjustments, if needed, and to bridge data from studies previously conducted with Process 1 patritumab to studies to be conducted with Process 2 patritumab.
The hypothesis for this study is that the pharmacokinetics of Process 2 patritumab will be comparable to those of Process 1 patritumab.
研究概览
详细说明
Process 2 patritumab will be administered intravenously as a single, loading dose of 18 mg/kg over approximately 60 minutes at Cycle 1 Day 1 followed by 9 mg/kg administered every 21 days as a maintenance dose starting at Cycle 2 Day 1.
This study will be conducted in 2 phases: a main study and an extension phase.
The PK profile of Process 2 patritumab will be compared to historical data for Process 1 patritumab.
Specifically, the PK parameters (AUC0-21d and Cmax as primary endpoints) for Process 2 patritumab 18 mg/kg (loading dose) will be compared to the PK parameters of Process 1 patritumab 18 mg/kg.
Process 2 patritumab serum concentrations will be compared to Process 1 patritumab serum concentrations collected in the Phase 1 and Phase 2 studies by population PK methods and will be reported separately.
研究类型
介入性
注册 (实际的)
17
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
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Florida
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Tampa、Florida、美国、33612
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Oklahoma
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Oklahoma City、Oklahoma、美国、73104
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Texas
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San Antonio、Texas、美国、78229
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Must have a pathologically documented advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available, or for which the subject refuses standard therapy.
- Must have a tumor type that is known to express HER3. These tumors include breast, lung, prostate, ovarian, cervical, endometrial, gastric, pancreatic, bladder, head and neck, liver, colon, and esophageal cancer. Other tumors will be considered based on emerging HER3 expression data.
- Must be competent and able to comprehend, sign, and date an IRB-approved ICF (including HIPAA authorization, if applicable) before performance of any study-specific procedures or tests.
- Must have an ECOG performance status of ≤ 2
Women must be one of the following:
- Postmenopausal (having had no menstrual period for a minimum of 12 months) or surgically sterile, or
- If of childbearing potential, must have been willing to use maximally effective birth control during the period of therapy and use contraception for 6 months following the last investigational drug infusion and must have had a negative urine or serum pregnancy test upon entry into the study.
- Men must be surgically sterile or willing to use a double-barrier contraception method upon enrollment, during the course of the study, and for 6 months following the last investigational drug infusion.
Have hematological function, as follows:6. Men
- Absolute neutrophil count of ≥ 1.5 × 109/L
- Platelet count ≥ 100 × 109/L
- Hemoglobin ≥ 9 g/dL
Have renal function, as follows:
- Calculated creatinine clearance rate (CrCl) ≥ 60 mL/minute using the modified Cockcroft-Gault equation or serum creatinine ≤ 1.5 × ULN.
Have hepatic function, as follows:
- AST ≤ 2.5 × ULN (if liver metastases are present, < 5 × ULN)
- ALT ≤ 2.5 × ULN (if liver metastases are present, < 5 × ULN)
- Alkaline phosphatase ≤ 2.5 × ULN (if bone or liver metastases are present, < 5 × ULN)
- Bilirubin ≤ 1.5 × ULN
- Prothrombin time (PT) or partial thromboplastin time (PTT) ≤ 1.5 × ULN
Exclusion Criteria:
- Have a history of lymphoma, leukemia, or other hematopoietic malignancy.
- Have Have autologous or allogeneic stem cell transplant.
- Have any comorbid medical condition that would increase the risk of toxicity in the opinion of the investigator or sponsor.
- Have untreated or symptomatic brain metastasis.
- Have unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE Version 4.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia. Subjects with irreversible Grade 2 toxicity may be eligible as per discretion of the investigator and sponsor (e.g., Grade 2 chemotherapy-induced neuropathy).
- Have uncontrolled hypertension (diastolic blood pressure > 100 mmHg or systolic blood pressure > 140 mmHg). It is permissible for the subject to receive treatment with antihypertensive medication to maintain blood pressure within the required parameters.
- Have clinically significant ECG changes that obscure the ability to assess the RR, PR, QT, QT interval corrected for heart rate (QTc), and QRS interval. Subjects with left bundle branch block, atrial fibrillation and use of cardiac pacemaker specifically will be excluded.
- Have ascites or pleural effusion requiring chronic medical intervention.
- Have a history of bleeding diathesis.
- Have had a myocardial infarction within 1 year before enrollment, symptomatic CHF (New York Heart Association > Class II;), unstable angina, or unstable cardiac arrhythmia requiring medication.
- Use of amiodarone within 6 months prior to enrollment.
- Concurrent use of antiarrhythmic medications with the exception of beta blockers for treatment of hypertension.
- Subjects who are receiving drugs that may affect QTc (e.g., quinidine or moxifloxacin).
- QTc interval > 450 msec on the average of the triplicate readings by Friderica's formula on 2 successive screening measurements (second measurement is required if first measurement is > 450 msec).
- Have a LVEF < 50%.
- Have anthracycline exposure greater than 360 mg/m2.
- Have a history of chronic hepatitis or known active infection with hepatitis B virus or hepatitis C virus.
- Personal or family history of long-QT syndrome.
- Have known infection with or a history of testing positive for human immunodeficiency virus (HIV).
- Had treatment with anticancer therapy (6 weeks for nitrosoureas and mitomycin C chemotherapies and 2 weeks for small molecule tyrosine kinase inhibitors), antibody therapy, retinoid therapy, or hormonal therapy within 4 weeks before study Day 1. Prior and concurrent use of hormone replacement therapy or the use of gonadotropin releasing hormone modulators for prostate cancer is permitted.
- Had therapeutic or palliative radiation therapy within 4 weeks before enrollment (in addition, he/she must have had resolution of any significant AEs from radiation therapy at least 2 weeks before enrollment).
- Have concurrent or previous (within 1 week of study Day 1) anticoagulation therapy, except low-dose warfarin (≤ 2 mg/day) or low-dose, low-molecular weight heparin for prophylaxis against central venous catheter thrombosis or deep vein thrombosis.
- Have participated in clinical drug trials within 4 weeks before enrollment.
- Have had major surgery within 4 weeks before enrollment.
- Is currently participating in other investigational procedures.
- Has any disorder that compromised the ability of the subject to give written informed consent and/or comply with study procedures.
- Has known sensitivity to any of the products to be administered during dosing or known allergy to the excipients or investigational drugs.
- Has active infection within 2 weeks before enrollment unless there was a discussion with the sponsor and an agreement was reached that the recent infection would not affect the subject's participation in the study.
- Has previously received an anti-HER3 targeted antibody, including patritumab.
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
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 |
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实验性的:Process 2 patritumab
Process 2 patritumab 18 mg/kg (loading dose) on Day 1 of Cycle 1 followed by Process 2 patritumab 9 mg/kg (maintenance dose) once every 21 days starting on Day 1 of Cycle 2 through Cycle 5.
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其他名称:
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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 |
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AUC (0-21 day) of Patritumab
大体时间:5 Cycles, each of which lasts 21 Days
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AUC (0-21 day) of patritumab obtained after a single infusion of Process 2 patritumab 18 mg/kg (loading dose)
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5 Cycles, each of which lasts 21 Days
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Cmax of Patritumab
大体时间:5 Cycles, each of which lasts 21 Days
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Cmax of patritumab obtained after a single infusion of Process 2 patritumab 18 mg/kg (loading dose)
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5 Cycles, each of which lasts 21 Days
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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volume of distribution [Vz]
大体时间:5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters volume of distribution [Vz]
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5 Cycles, each of which lasts 21 Days
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Safety and Tolerability of Process 2 patritumab - (electrocardiograms [ECG)
大体时间:5 Cycles, each of which lasts 21 Days
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To assess the safety and tolerability of Process 2 patritumab (electrocardiograms [ECG)
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5 Cycles, each of which lasts 21 Days
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Antibody Formation
大体时间:5 Cycles, each of which lasts 21 Days
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To characterize the formation of antibodies to patritumab human antihuman antibodies (HAHA) after infusion of Process 2 patritumab
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5 Cycles, each of which lasts 21 Days
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Concentration patritumab at 504 hours
大体时间:5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameter concentration of patritumab at 504h [C504]
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5 Cycles, each of which lasts 21 Days
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AUC to infinity [AUC0-inf]
大体时间:5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters AUC to infinity [AUC0-inf]
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5 Cycles, each of which lasts 21 Days
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time to Cmax (Tmax)
大体时间:5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters time to Cmax (Tmax)
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5 Cycles, each of which lasts 21 Days
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concentration at the end of infusion (Ceoi)
大体时间:5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters concentration at the end of infusion (Ceoi)
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5 Cycles, each of which lasts 21 Days
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terminal elimination half-life (t 1/2)
大体时间:5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters terminal elimination half-life (t 1/2)
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5 Cycles, each of which lasts 21 Days
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clearance (CL)
大体时间:5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters clearance (CL)
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5 Cycles, each of which lasts 21 Days
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trough concentration (Ctrough)
大体时间:5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters trough concentration (Ctrough)
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5 Cycles, each of which lasts 21 Days
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echocardiograms/multi-gated acquisition [MUGA] scans of Process 2 patritumab
大体时间:5 Cycles, each of which lasts 21 Days
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To assess the safety and tolerability of Process 2 patritumab echocardiograms/multi-gated acquisition [MUGA] scans
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5 Cycles, each of which lasts 21 Days
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adverse events [AEs] of Process 2 patritumab
大体时间:5 Cycles, each of which lasts 21 Days
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To assess the safety and tolerability of Process 2 patritumab adverse events [AEs] of Process 2 patritumab
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5 Cycles, each of which lasts 21 Days
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2013年6月1日
初级完成 (实际的)
2013年10月1日
研究完成 (实际的)
2014年4月1日
研究注册日期
首次提交
2013年6月12日
首先提交符合 QC 标准的
2013年9月30日
首次发布 (估计)
2013年10月8日
研究记录更新
最后更新发布 (估计)
2014年5月14日
上次提交的符合 QC 标准的更新
2014年5月13日
最后验证
2014年5月1日
更多信息
与本研究相关的术语
关键字
其他研究编号
- U31287-A-U105
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.
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