Safety/Tolerability Study of AV-412 in Subjects With Refractory or Relapsed Solid Tumor Malignancies
A Phase 1, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of Daily Oral Administration of AV-412 in Patients With Refractory or Relapsed Solid Tumor Malignancies
研究概览
详细说明
Although progress has been made, patients with malignancies often either progress after the traditional approach of chemotherapy, surgery, or radiotherapy, or are not candidates for these approaches because of the advances stage of disease. Novel therapies that may offer greater potential than those currently available are urgently needed.
AV 412 is a potent inhibitor of human epidermal growth factor family receptor tyrosine kinases (TKIs) and represents a growing class of anti-cancer agents. The recent introduction of TKIs has opened the door to new approaches to cancer treatment in which the goals of therapy are to halt disease progression, ameliorate symptoms, and improve patient quality of life. AV412 may inhibit growth of solid tumors, with fewer and less debilitating side effects.
This study is designed to determine the safety, tolerability and maximum tolerated dose of daily oral administration of AV 412. Patients will be assigned to escalating drug dose cohorts to determine the optimal dose. Evaluations to determine tolerability include PK, PD, and the adverse events which occur during the course of study drug administration.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
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
Criteria for Inclusion:
- ≥ 18 year old males or females
- Documented measurable or evaluable solid tumor malignancy that is relapsed, refractory, locally advanced, or metastatic
Patients entered to MTD Cohort B must have:
- Histologically or cytologically confirmed NSCLC
- No prior therapy with erlotinib, gefitinib, or any other EGFR-kinase inhibitor
- Previously documented exon 19 deletion and/or exon 21 L858R mutations
- Measurable disease according to RECIST
- Disease that is currently refractory to, or not amenable to, standard therapy
- Disease that is currently not amenable to surgical intervention, due to either medical contraindications or nonresectability of the tumor
- Karnofsky performance status ≥ 70%, life expectancy ≥ 3 months
- No childbearing potential or use of effective contraception by all fertile male and female patients, during the study and for 3 months after the last dose of study drug
- Ability to give written informed consent
Criteria for Exclusion:
- Pregnant or lactating women
- Primary CNS malignancies; active CNS metastases
- Hematologic malignancies (includes: leukemia, any form; lymphoma; and multiple myeloma)
Active second malignancy or history of another malignancy within 2 years with the exception of:
- Treated, non-melanoma skin cancers
- Treated CIS of the breast or cervix
- Controlled, superficial bladder carcinoma
- T1a or b prostate carcinoma involving < 5% of resected tissue and PSA within normal limits (WNL)
Any of the following hematologic abnormalities:
- Hemoglobin ≤ 9.0 g/dL
- ANC < 1,500 per mm3
- Platelet count < 100,000 per mm3
Any of the following serum chemistry abnormalities:
- Total bilirubin > 1.5 × the ULN
- AST or ALT ≥ 3 × the ULN (≥ 5 × if due to hepatic involvement by tumor)
- Serum albumin < 2.5 g/dL
- Creatinine ≥ 1.5 × ULN (or calculated CLCR < 50 mL/min/1.73 m2)
Significant cardiovascular disease, including:
- CHF requiring therapy
- Ventricular arrhythmia requiring therapy
- Any conduction disturbance (including patients with QTc interval prolongation > 0.47 sec, history of a severe arrhythmia, or history of a familial arrhythmia [eg, WPW])
- Angina pectoris requiring therapy
- LVEF < 50% by MUGA or Echocardiogram
- Uncontrolled HTN
- MI within 6 months of study entry
- NYHA > Class I
Significant gastrointestinal abnormalities, including:
- Requirement for IV alimentation
- Prior surgical procedures affecting absorption
- Active peptic ulcer disease
- ≥Grade 2 diarrhea due to any etiology
Known history of significant ophthalmologic abnormalities, including:
- Severe dry-eye syndrome
- Keratoconjunctivitis sicca
- Sjogren's syndrome
- Severe exposure keratopathy
- Disorders increasing risk for epithelium-related complications
- Serious/active infection; infection requiring parenteral antibiotics
- Inadequate recovery from prior antineoplastic therapy
- Inadequate recovery from any prior surgical procedure; major surgical procedure within 2 weeks
- Life-threatening illness or organ system dysfunction compromising safety evaluation
- Psychiatric disorder, altered mental status precluding informed consent or necessary testing
- Inability to comply with protocol requirements
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 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:A
Daily oral administration of AV-412
|
Solid oral dosage; 4 dosage strengths; 25, 50, 100, or 200 mg per capsule Dosing Frequency: Once daily dosing for 4 weeks (4 weeks equals 1 cycle)
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
To evaluate the safety, tolerability, and dose-limiting toxicities (DLT), and determine the maximum tolerated dose (MTD) of AV-412 when administered once daily by the oral route for 4 weeks (4 weeks equals one dosing cycle)
大体时间:one year
|
one year
|
次要结果测量
结果测量 |
大体时间 |
---|---|
To characterize the pharmacokinetic (PK) profile of AV-412 in all patients. Extensive PK collection and assay to be performed in expanded MTD Cohorts
大体时间:18 months
|
18 months
|
Evaluate potential pharmacodynamic (PD) markers of AV-412 action, in expanded MTD Cohorts ONLY
大体时间:two years
|
two years
|
Preliminary evaluation of the antineoplastic activity of AV-412 (assessed by evidence and duration of disease stabilization or objective response, and time to disease progression)
大体时间:two years
|
two years
|
合作者和调查者
调查人员
- 首席研究员:Manuel Hidalgo, MD, PhD、Johns Hopkins University
- 首席研究员:Justina L Martinez, MD、Hospital Universitatrio Austral
- 首席研究员:Carmen S. Puparelli, MD、Instituto Médico Especializado Alexander Fleming
- 首席研究员:Belén R. Viquiera, M.D.、Centro Integral Oncológica Clara Campal
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
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 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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AV-412的临床试验
-
University Hospital, Gentofte, CopenhagenRigshospitalet, Denmark; Lund University Hospital未知
-
Columbia UniversityNational Institute of Neurological Disorders and Stroke (NINDS)完全的
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Northwestern UniversityNational Institute on Aging (NIA)招聘中
-
Vasomune Therapeutics, Inc.招聘中
-
Avid RadiopharmaceuticalsEli Lilly and Company完全的