BIBF 1120 and RAD001 in Solid Tumors - Phase I (BARIS)
2016年5月19日 更新者:Prof. Dr. Juergen Wolf、University of Cologne
BARIS - BIBF1120 and RAD001 in Solid Tumors. A Phase I Trial to Evaluate the Safety and Tolerability of Combined BIBF 1120 and RAD001 in Solid Tumors and to Determine the Maximum Tolerated Dose (MTD) of the Combination
BIBF1120 and RAD001 in solid tumors
研究概览
详细说明
A phase I trial to evaluate the safety and tolerability of combined BIBF 1120 and RAD001 in solid tumors and to determine the maximum tolerated dose (MTD) of the combination
研究类型
介入性
注册 (实际的)
18
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
-
-
NRW
-
Cologne、NRW、德国、50937
- University Hospital of Cologne
-
-
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:
- Histologically or cytologically proven solid tumor disease after failure of standard therapy regimen(s)
- Age > 18 years.
- ECOG performance status 0 to 1.
- Life expectancy of at least 12 weeks.
- Subjects with at least one measurable (CT or MRI) lesion.
Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days prior to screening:
- Hemoglobin > 9.0 g/dl
- Absolute neutrophil count (ANC) >1,500/mm3
- Platelet count ³ 100,000/μl
- Total bilirubin within normal limits
- ALT and AST < 1.5 x upper limit of normal ( or < 2.5 x upper limit of normal in patients with liver involvement)
- PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]
- Serum creatinine < 1.5 x upper limit of normal or creatinine clearance (CrCl) ≥ 50 ml/min calculated by either Cockcroft-Gault or by 24 hours urine collection
- More than 14 days since previous chemotherapy, radiotherapy and surgery
- Negative urine or serum HCG in women of childbearing potential
- Signed and dated informed consent before the start of specific protocol procedures
Exclusion Criteria:
- Limited number of prior lines of treatment (including surgery and radiotherapy, if part of the standard therapy of the respective tumor entity)
- Prior treatment with BIBF 1120 or any other VEGFR inhibitor (bevacizumab is allowed)
- Prior treatment with RAD001 or any other mTOR inhibitor
- Known hypersensitivity to the trial drugs, to their excipients or to contrast media
- Chemo-, hormono-, radio-(except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 2 weeks prior to treatment with the trial drugs
- Persistence of clinically relevant therapy related toxicity from previous chemo and/or radiotherapy
- Active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anticonvulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before trial drug administration) or leptomeningeal metastases (documented by lumbar puncture)
- History of cardiac disease: congestive heart failure >NYHA class 2; active coronary artery disease (CAD), (MI more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring antiarrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of BIBF1120 or RAD001 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- History of HIV infection or previously seropositive for the virus
- History of Hepatitis B or/and C or previously seropositive for the Hepatitis B or/and C virus
- Radiographic evidence of cavitary or necrotic tumors
- Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels
- Treatment with other investigational drugs or treatment in another clinical trial within the past 30 days before start of therapy or concomitantly with the trial
- Patients with seizure disorder requiring enzyme-inducing antiepileptics
- Therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous devise) or antiplatelet therapy (except for low-dose therapy with acetylsalicylic acid ≤325mg per day)
- Major injuries within the past 10 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period
- Evidence or history of bleeding diasthesis or thrombosis, and known inherited predisposition to bleeding or thrombosis
- Proteinuria CTC AE grade 2 or greater
- Active serious infections
- Patients undergoing renal dialysis
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry
- Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastrointestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study
- Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least three months after end of active therapy
- Pregnancy or breast feeding
- Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
- Active alcohol or drug abuse
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 |
---|---|
实验性的:BIBF 1120 + RAD001
|
Dose level 1: 1x 5mg Everolimus/d + 2x 150mg BIBF 1120/d.
Dose level 2: 1x 5mg Everolimus/d + 2x 200mg BIBF 1120/d.
Dose level 3: 1x 10mg Everolimus/d + 2x 200mg BIBF 1120/d
其他名称:
|
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 determine the maximum tolerated dose (MTD) of RAD001 in combination with BIBF 1120 (150mg bid or 200mg bid) (endpoint: dose-limiting toxicities)
大体时间:Every visit
|
Documentation an estimation of adverse events
|
Every visit
|
To evaluate the tolerability of BIBF1120 and RAD001 in combination (endpoints: assessment of adverse events (AEs) according to CTC-AE V4.0)
大体时间:Every visit during the study
|
Documentation an estimation of adverse events
|
Every visit during the study
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
To evaluate the clinical efficacy of the combination descriptively (endpoints: RR, progression free survival (PFS), overall survival (OS))
大体时间:Baseline and every six weeks during the study, after study every 6 months
|
CT will be done for evaluation of RR and PFS on day 57 and then every 6 weeks until progression. For overall survival a telephone call every six months after study is continuation will be done |
Baseline and every six weeks during the study, after study every 6 months
|
To analyze individual BIBF1120 pharmacokinetic (PK) parameters at steady-state (ss) of monotherapy and PK parameters of both BIBF1120 and RAD001 at ss of combination
大体时间:day 14, day 29
|
Blood collection for pharmacokinetic analysis
|
day 14, day 29
|
To assess changes in tumor vasculature a) early under BIBF1120 monotherapy, b) at ss of BIBF1120 monotherapy and c) at ss of combination therapy using dynamic contrast-enhanced MRI (DCE-MRI) (endpoints: IAUC, Ktrans, Kep, Ve)
大体时间:baseline, day 3, day 14, day 29
|
DCE MRI will be done
|
baseline, day 3, day 14, day 29
|
To correlate the clinical outcome with FGFR1-amplification status (endpoints: see above for clinical parameters)
大体时间:Screening
|
Documentation of histology
|
Screening
|
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。
调查人员
- 首席研究员:Juergen Wolf, Prof.、University Hospital of Cologne
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
2012年7月1日
初级完成 (实际的)
2014年10月1日
研究完成 (实际的)
2016年5月1日
研究注册日期
首次提交
2011年5月5日
首先提交符合 QC 标准的
2011年5月5日
首次发布 (估计)
2011年5月6日
研究记录更新
最后更新发布 (估计)
2016年5月20日
上次提交的符合 QC 标准的更新
2016年5月19日
最后验证
2016年5月1日
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.
实体瘤的临床试验
-
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
Everolimus + BIBF 1120的临床试验
-
Boehringer Ingelheim完全的
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)完全的复发性子宫体癌 | 子宫内膜透明细胞腺癌 | 子宫内膜浆液性腺癌 | 子宫内膜未分化癌 | 子宫内膜腺癌 | 子宫内膜移行细胞癌 | 子宫内膜粘液腺癌 | 子宫内膜鳞状细胞癌 | 恶性子宫体混合性上皮和间质肿瘤美国
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)完全的
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); Boehringer Ingelheim完全的
-
Boehringer Ingelheim完全的肺纤维化阿根廷, 澳大利亚, 比利时, 巴西, 保加利亚, 加拿大, 智利, 中国, 捷克共和国, 法国, 德国, 希腊, 匈牙利, 爱尔兰, 意大利, 大韩民国, 墨西哥, 荷兰, 葡萄牙, 俄罗斯联邦, 南非, 西班牙, 台湾, 火鸡, 英国
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); Boehringer Ingelheim; National Comprehensive Cancer Network完全的
-
University College, LondonBoehringer Ingelheim完全的