Phase I Trial of Vandetanib Combined With 131I-mIBG to Treat Patients With Advanced Phaeochromocytoma and Paraganglioma (VIBRaNT)
A Phase I Trial of Vandetanib Combined With 131I-mIBG Radiotherapy in Patients With Neuroendocrine Tumours, Advanced Phaeochromocytoma and Paraganglioma
研究概览
详细说明
VIBRaNT is a registered phase I trial in patients with locally advanced or metastatic phaeochromocytoma or paraganglioma, not amenable to surgical resection.
Patients will receive vandetanib (an inhibitor of VEGF, EGFR and RET tyrosine kinase) in combination with standard radiation therapy Iodine-131 labelled Meta-iodobenzylguanidine (131I-mIBG).
Vandetanib and 131I-mIBG will be given in 12-weekly cycles: 131I-miBG will be given on day 1 of each cycle and vandetanib will started on day 1 of each cycle and continue to be taken once every day. The phase I trial aims to determine with recommended phase II dose of vandetanib (either 100, 200 or 300 mg once daily) - the dose of vandetanib that patients will receive will depend on the dose under investigation at the time of patient registration.
The vandetanib dose will be determined by the Modified Continual Reassessment Method (mCRM) - a toxicity model which described the probability of a toxicity occurring at each dose level, which is based on clinical judgement and any available toxicity data.
研究类型
阶段
- 阶段1
联系人和位置
学习地点
-
-
-
London、英国
- University College London Hospitals NHS Foundation Trust
-
London、英国
- Guy's and St Thomas' NHS Foundation Trust
-
London、英国
- The Christie NHS Foundation Trust
-
-
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
Inclusion Criteria:
- Histopathological/cytological diagnosis of advanced phaeo/PG defined as patients with local or metastatic disease not amenable to surgical resection, or R1 resection post original surgical debulking
- Positive 123I-mIBG diagnostic scan
- Stable blood pressure (<140/90mmHg), if appropriate, on anti-hypertensive therapy
- No previous systemic chemotherapy within 3 months prior to registration
- No previous mIBG therapy within 12 months prior to registration (previous cumulative activity must not exceed 15 GBq)
- Measurable disease (RECIST v1.1)
- WHO performance status 0 or 1
- Age ≥ 18
- Estimated life expectancy > 3 months.
- Adequate bone marrow function: Haemoglobin ≥ 100 g/L, White Blood Cell ≥ 3.0 x 10^9/L, Absolute neutrophil ≥ 1.5 x 10^9/L, Platelet ≥ 100 x 10^9/L
- Adequate liver function: Total bilirubin ≤1.5 x Upper Limit of Normal (ULN); ALT/AST and ALP≤ 2.5 x ULN or ≤ 5 x ULN if related to liver metastases
- Adequate renal function: Serum urea and creatinine < 1.5x ULN AND Calculated creatinine clearance (GFR) ≥50 mL/min. If the calculated GFR is below 50, isotope clearance test is required to confirm GFR ≥50 mL/min
- Electrolytes: Potassium ≥ 4.0 mmol/L and ≤ 5.5 mmol/L, Magnesium ≥ Lower Limit of Normal and ≤ 1.23 mmol/L, Corrected calcium within institution normal range
- Negative pregnancy test for women of child-bearing potential AND be using adequate barrier contraception, which must be continued for 12 months after completion of treatment (male patients must also agree to use barrier contraception during the trial and for 12 months after completion of treatment)
- Able to swallow oral medication
- Capable of giving written informed consent
Exclusion Criteria:
- Patients undergoing current treatment with curative intent
- Previous or current malignancies of other histological types within the last 5 years (exceptions listed in the trial protocol)
- Any prior exposure to VEGF, EGFR or RET inhibitors or history of hypersensitivity to vandetanib or any excipient agents
- Evidence of severe or uncontrolled systemic diseases or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial
- Evidence of active uncontrolled infection (patients on antibiotics are eligible)
- Chronic gastrointestinal disease (e.g. Inflammatory Bowel Disease) or significant bowel resection that would preclude adequate absorption
Cardiovascular exclusion criteria (complete list provided in the trial protocol):
- Significant cardiac event (myocardial infarction), New York Heart Association Class II or above, within 12 weeks before registration, or presence of cardiac disease that in the opinion of the investigator increased the risk of ventricular arrhythmia
- Prior or current cardiomyopathy
- Baseline LVEF < 40% as measured by ECHO/MUGA
- Atrial fibrillation with heart rate >100 bpm
- Unstable ischaemic heart disease (myocardial infarction within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly)
- History of arrhythmia that was symptomatic or required treatment
- QTcB prolongation >480 ms at baseline
- QT prolongation with other medications that required discontinuation of that medication
- Any psychiatric or other disorder likely to impact on informed consent or ability to manage isolation
- Major surgery within 28 days prior to registration
- Brain metastases or spinal cord compression, unless treated at least four weeks before the first dose and stable without steroid treatment for 10 days
- Any concomitant medications that may affect QTc, induce or inhibit CYP3A4 function (with the exception of somatostatin or somatostatin analogue) and/or prohibited medications
- Women who are pregnant or lactating
学习计划
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:Vandetanib + 131I-mIBG
Vandetanib (100, 200 or 300 mg once daily) in combination with 131I-mIBG radiation therapy (activity to be prescribed to deliver whole body absorbed dose of 0.5 Gy) on day 1 of each 12-weekly cycle. Patients will receive up to 4 cycles of vandetanib in combination with 131I-mIBG. |
100 mg, 200 mg or 300 mg taken once a day during each 12-weekly cycle
其他名称:
Activity will be prescribed to deliver whole body absorbed dose of 0.5 Gy (+/-10%)
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 |
---|---|---|
Occurrence of Dose Limiting Toxicity
大体时间:From start of cycle 1 to end of cycle 1 (each cycle = 12 weeks)
|
Detailed adverse event monitoring will be conducted according to CTCAE v4.03.
Dose Limiting Toxicity (DLT) is defined as any adverse event or laboratory abnormality detailed in the trial protocol, that is considered to be highly probable or probable trial treatment related and commencing anytime during the DLT evaluation period (from start of cycle 1 to cycle 1 week 12).
Adverse Events include: Haematological, Clinical Chemistry, Cardiovascular, Gastrointestinal, Skin.
|
From start of cycle 1 to end of cycle 1 (each cycle = 12 weeks)
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Objective response
大体时间:Determined using imaging scans performed at baseline (registration), then every 3 months after start of treatment until disease progression up to 3 years from date of registration
|
Response will be assessed according to RECIST v1.1.
Confirmation of complete or partial response is not required.
Stable disease will be considered the best response only is a second assessment has been carried out which confirmed stable disease at least 4 weeks after trial entry.
Assessment will be determined using CT scans and 123I-mIBG scans performed at baseline, then every 3 months after start of treatment until disease progression (up to 3 years from registration)
|
Determined using imaging scans performed at baseline (registration), then every 3 months after start of treatment until disease progression up to 3 years from date of registration
|
Occurrence and Severity of Adverse Events
大体时间:From date of registration until 30 days after completion of trial treatment (vandetanib and/or 131I-mIBG)
|
Will include all grade 1-5 adverse events.
|
From date of registration until 30 days after completion of trial treatment (vandetanib and/or 131I-mIBG)
|
Progression Free Survival
大体时间:From date of registration to date of documented disease progression or death from any cause, whichever comes first, assessed up to 3 years from date of registration
|
Progression-free survival will be calculated from the date of trial entry to the date of documented disease progression, or death from any cause.
Where progression is suspected and subsequently confirmed by scans, the date of documented suspected progression will be used.
|
From date of registration to date of documented disease progression or death from any cause, whichever comes first, assessed up to 3 years from date of registration
|
合作者和调查者
调查人员
- 首席研究员:Christina Thirlwell、University College London (UCL) Cancer Institute
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
与本研究相关的术语
关键字
其他研究编号
- UCL/12/0499
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.