Phase II Study of Nilotinib Efficacy in Pigmented Villo-Nodular Synovitis/ Tenosynovial Giant Cell Tumour (PVNS/TGCT)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 15
- 主要终点
- the non progression rate after 12 weeks (3 months) of treatment, based on the response evaluated by CT scan or MRI according to RECIST criteria (RECIST version 1.1) and validated by a central review committee.
研究概览
简要总结
The purpose of this study is to explore the efficacy of nilotinib as a treatment of patients with progressive or relapsing pigmented villo-nodular synovitis / tenosynovial giant cell tumour (PVNS/TGCT) who cannot be treated by surgery.
The primary objective of the study will be to determine the efficacy of 12 weeks (3 months) of nilotinib treatment as measured by the non progression rate (Complete response + Partial Response + Stable disease according to Response Evaluation Criteria In Solid Tumours - RECIST version 1.1) in patients with progressive or relapsing PVNS/TGCT who cannot be treated by surgery.
this study is an international, multicentre, non-randomized, open-label phase II clinical trial with a Bayesian design.
A maximum sample size of 50 patients will be included in the study
详细描述
A key secondary objective of the study will be to determine the efficacy of 24 weeks (6 months) of nilotinib treatment as measured by the non progression rate (Complete response + Partial Response + Stable disease according to Response Evaluation Criteria In Solid Tumours - RECIST version 1.1) in patients with progressive or relapsing PVNS/TGCT who cannot be treated by surgery.
This key secondary objective was defined for the purpose of a further analysis (not described in this protocol) which will pool the data of the PVNS study with those of a similar concomitant study conducted in the US and Australia.
The other secondary objectives will be:
To evaluate the efficacy of nilotinib according to:
- The objective tumour response rate (Complete response + Partial Response according to RECIST version 1.1) after 12 weeks of treatment
- The duration of treatment response
- The best overall response obtained during the study
- The progression-free survival (PFS)
- The time to progression (TTP)
- The time to treatment failure (TTF)
- The proportion of patients with an operable tumour after nilotinib exposure according to investigator evaluation
- The description of concomitant treatments use
- The correlation between trough levels of nilotinib and objective tumour response To assess the safety of nilotinib for PVNS/TGCT patients
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
- •Age > 18 years
- •Histologically confirmed diagnosis of inoperable progressive or relapsing PVNS/TGCT OR resectable tumour requesting mutilating surgery
- •Demonstrated progressive disease in the last 12 months
- •At least one measurable site of disease on MRI/CT scan according to RECIST criteria (RECIST version 1.1) based on investigator's assessment
- •WHO Performance status of 0, 1 or 2
- •Adequate organ, electrolyte and marrow function, defined as the following: serum bilirubin > or =1.5 x ULN, ALT and AST < or = 2.5 x ULN, serum creatinine < or = 1.5 x ULN or creatinine clearance > or = 50 mL/min, absolute neutrophil count (ANC) > or = 1.5x109/L, platelets > or = 100x109/L, serum lipase < or =1.5 x ULN, magnesium ≥ lower limit of normal (LLN) and potassium ≥ LLN
- •Prior adequate physical examination including weight, height, ECOG PS and vital signs (systolic and diastolic blood pressure, heart rate after at least 5 minutes in supine position)
- •Signed written informed consent form
- •Covered by a medical insurance (in countries where applicable)
排除标准
- •Pregnant or lactating female or female of child-bearing potential not employing adequate contraception during the study and for up to three months following termination of the study
- •Known hypersensitivity to nilotinib or to any of the excipients, galactose intolerance, lactase deficiency or glucose-galactose malabsorption prior to enrollment
- •Acute or chronic uncontrolled liver disease, or severe renal disease
- •Impaired cardiac function, including:
- •LVEF<50% or below the institutional lower limit of the normal range (whichever is higher) as determined by echocardiogram or MUGA scan
- •History or signs of prior myocardial infarction
- •History of unstable angina
- •Congenital long QT prolongation
- •Personal history of unexplained syncope
- •QTc interval ≥ 450 msec on screening ECG
- •Other clinically significant heart disease (e.g. bradycardia, congestive heart failure or uncontrolled hypertension)
- •Patient with family history of long QT syndrome, of unexplained syncope or of unexplained sudden death
- •Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. uncontrolled diabetes, active or uncontrolled infection, history of pancreatitis
- •History of non-compliance to medical regimens
- •Concomitant treatment with medicinal products that induce CYP3A4 (e.g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or St. John's Wort), or that inhibit the CYP3A4 activity (e.g. ketoconazole, itraconazole, voriconazole, erythromycin, clarithromycin, telithromycin)
- •Concomitant treatment with warfarin
- •Concomitant treatment with anti-arrhythmic drug (e. g. amiodarone, sotalol, disopyramide, quinidine, procainamide) or medication that prolongs the QT interval (e.g. chloroquine, chlorpromazine, domperidone, droperidol, halofantrine, haloperidol, methadone, pentamidine, pimozide, thioridazine)
- •Prior treatment with imatinib except if no progression was demonstrated
研究组 & 干预措施
Nilotinib
干预措施: Tasigna (Drug)
结局指标
主要结局
the non progression rate after 12 weeks (3 months) of treatment, based on the response evaluated by CT scan or MRI according to RECIST criteria (RECIST version 1.1) and validated by a central review committee.
时间窗: after 12 weeks (3 months) of treatment
次要结局
- Proportion of patients with an operable tumour after nilotinib exposure according to investigator evaluation(at the end of the study (last visit))
- Concomitant treatment use during the study(during the study)
- Non progression rate after 24 weeks (6 months) of treatment, based on the response evaluated by CT scan or MRI according to RECIST criteria (RECIST version 1.1).(after 24 weeks (6 months) of treatment)
- Objective tumour response according to RECIST version 1.1 (CR and PR) after 12 weeks of treatment(after 12 weeks of treatment)
- Duration of response(during the study)
- Best overall response(during the study)
- Progression-free survival(during the study)
- Time to progression(during the study)
- Time to treatment failure(during the study)
- Non progression rate after 12 weeks of treatment, based on the response evaluated locally by the investigator in charge using CT scan or MRI and according to RECIST criteria (RECIST version 1.1)(after 12 weeks of treatment)
- Correlation between trough level of nilotinib at 6 weeks and 12 weeks and objective tumour response(at the end of the study)
- Safety evaluation will be based on overall safety profile characterized by type, frequency and severity (as graded using NCI-CTCAE V3.0) of adverse events.(at the end of the study)