Phase I Trial of Induction Dasatinib Therapy in Patients With Resectable Malignant Pleural Mesothelioma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Modulation of biomarker p-Src Tyr419 expression
研究概览
简要总结
The goal of this clinical research study is to learn how dasatinib affects biomarker levels in patients with malignant pleural mesothelioma that may be able to be removed by surgery. The safety and effectiveness of this drug will also be studied.
This research study is financially supported by the United States Department of Defense.
详细描述
The Study Drug Dasatinib is designed to decrease the activity of one or more proteins that are responsible for the uncontrolled growth of tumor cells. This may cause the tumor cells to die.
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take 2 dasatinib tablets by mouth 2 times a day for the 4 weeks before surgery (in the morning and 12 hours later). Dasatinib may be taken with or without food, but should be swallowed with at least 1 cup (8 ounces) of water. A light meal is not required, but may help you avoid getting a stomach ache when you take your dose. Tablets must be swallowed whole and may not be broken. If vomiting occurs within 30 minutes of swallowing the tablet(s), you can take another dose. If you miss a dose of dasatinib, take it as soon as you remember on the same day. If you miss taking your dose for 12 hours, take your regular dose the next scheduled day (do not take double your regular dose to make up for the missed dose). You will be given a "pill diary" to write down when you take the study drug. You will be shown how to fill it out and asked to bring the diary with you to each clinic visit.
Study Visits:
On Days 21 and 28, the following tests and procedures will be performed:
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
- •Patients with potentially resectable malignant pleural mesothelioma, IMIG stage I-III
- •Subject, age >/= 18 years
- •Any patient who is able to tolerate general anesthesia for the extended surgical staging and the definitive surgical resection.
- •No prior chemotherapy for mesothelioma within the last 3 years
- •No prior radiation to the area of primary disease. Radiation to chest wall port sites is acceptable.
- •No prior targeted biologic therapy (i.e. EGFR inhibitors, VEGF inhibitors) within the last 3 years
- •Adequate Organ Function: a) Total bilirubin < 2.0 times the institutional Upper Limit of Normal (ULN), b) Hepatic enzymes (AST, ALT ) </= 2.5 times the institutional ULN, c) Serum Na, K+, Mg2+, Phosphate and Ca2+>/= Lower Limit of Normal (LLN), d) Serum Creatinine < 1.5 time the institutional ULN, e) Hemoglobin, Neutrophil count, Platelets, PT, PTT all Grade 0-1
- •Ability to take oral medication (dasatinib must be swallowed whole)
- •Women of childbearing potential (WOCBP) must have: A negative serum or urine pregnancy test (sensitivity </= 25IU HCG/L) within 72 hours prior to the start of study drug administration
- •Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped
- •Signed written informed consent including HIPAA according to institutional guidelines
排除标准
- •Malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 3 years.
- •Prior therapies to be excluded: any prior chemotherapy or targeted biologic therapy for mesothelioma used within the last 3 years
- •Concurrent medical condition which may increase the risk of toxicity, including: a) Clinically-significant coagulation or platelet function disorder (e.g. known von Willebrand's disease) b) Any disease which requires persistent anticoagulation therapy (and the patient may not be taken off the anti-coagulation safely) with coumadin, factor Xa inhibitors, or heparin (low-molecular weight, standard)
- •Cardiac Symptoms, consider the following: a) Uncontrolled angina, congestive heart failure or MI within (6 months), b) Diagnosed congenital long QT syndrome:
- •Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes),
- •Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec),
- •Subjects with hypokalemia or hypomagnesemia if it cannot be corrected
- •History of significant bleeding disorder unrelated to cancer, including: a) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), b) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies), c) Ongoing or recent (</= 3 months) significant gastrointestinal bleeding
- •Concomitant Medications, consider the following prohibitions: a) Drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib): A) quinidine, procainamide, disopyramide, B) amiodarone, sotalol, ibutilide, dofetilide, C) erythromycin, clarithromycin, D) chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide E) cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine. F) moxifloxacin, levofloxacin
- •The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is not recommended.The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy.a)Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy,b)Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia,c)Patient may not be receiving any prohibited CYP3A4 inhibitors,d)Patient may not be receiving any alternative herbal remedies during the dasatinib treatment period
- •Women: a) are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or, b) have a positive pregnancy test at baseline, or c) are pregnant or breastfeeding, d) Sexually active women of childbearing potential (WOCBP) must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized.,
- •continued from exclusion #8-: e) Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy., f) All WOCBP MUST have a negative pregnancy test prior to first receiving dasatinib. If the pregnancy test is positive, the patient must not receive dasatinib and must not be enrolled in the study.
- •Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
研究组 & 干预措施
Dasatinib
Dasatinib = BMS-354825, Sprycel
干预措施: Dasatinib (Drug)
结局指标
主要结局
Modulation of biomarker p-Src Tyr419 expression
时间窗: Weekly during treatment followed by 5-6 core biopsies during surgery.
McNemar's test used to compare the p-Src Tyr 419 expression before and after dasatinib treatment. The magnitude of modulation tested and quantified via paired-t test and Wilcoxon signed-rank test. For continuous data, paired-t test used for testing the biomarker modulation pre- and post-treatment.
次要结局
- Progression-free Survival(3 Years, or until disease progression.)