An Experimental Pilot Study to Investigate Changes in Catecholamine Synthesis and Metabolism in Patients With Molecularly Profiled Phaeochromocytoma and Paraganglioma Taking Belzutifan
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Tyrosine measurements
研究概览
简要总结
To investigate the impact of a medication called Belzutifan on the production and subsequent metabolism of adrenaline and noradrenaline collectively termed 'catecholamines'. The study aims to identify changes in the production and metabolism of catecholamines by measuring the substance which starts the chain of catecholamine metabolism called tyrosine in patients before, during and after 5 days of taking Belzutifan 120mg daily.
详细描述
This is a single centre, single arm, pilot interventional study aimed at identifying alterations in catecholamine synthesis and metabolism in 12 patients taking Belzutifan 120mg daily for five days. As this is a pilot and experimental study of a rare disease, sample size was not calculated. A study recruitment target of 12 patients was established based on the annual incidence of patients with catecholamine secreting PPGL attending our national referral centre.
There is an estimated annual incidence of 100-150 patients across all of England and an annual incidence of 15-20 patients attending Cambridge University Hospital per year.
The study protocol is 14 days. All patients will be recruited by the PI after informed consent and review of the study inclusion and exclusion criteria.
Germline genetic results performed as part of routine clinical care will be recorded for all patients. For those patients with negative germline genetic test results, tumour sequencing of available tissue or tumour tissue later removed (after the end of the study protocol) during surgery will be performed to investigate for somatic variants (genetic changes unique to the tumour cells) in specific genes which may influence how Belzutifan impacts catecholamine synthesis and metabolism.
The study protocol is 14 days including five days of intervention with Belzutifan 120mg daily for all patients. Baseline plasma tyrosine and plasma metanephrines will be performed on all patients (day 0) and at several time points after starting Belzutifan 120mg daily to examine for alterations in catecholamine metabolism. Recruited patients will attend daily for seven days and again on day 10 and day 14 and will be reviewed by the PI.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients > 18 years
- •Patients must have a biochemically confirmed diagnosis of a phaeochromocytoma or paraganglioma using plasma metanephrines or 24- hour urinary metanephrines and plasma or urinary metanephrines should be at least 1.5 times the upper limit of the normal reference range.
- •Female patients of child-bearing potential must have a negative serum pregnancy test result within 3 days before first administration of study drug
- •Able to provide informed consent
排除标准
- •Has hypoxia, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
- •Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass graft surgery (CABG) ≤6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted.
- •Has a co-existing malignancy (in addition to PPGL)
- •Has a Hb < 100g/dL
- •Is on medications which may interfere with belzutifan pharmacokinetics and that cannot be stopped for the duration of the study and for 7 days after the study period (everolimus, omeprazole, esomeprazole, Fluconazole, fluoxetine, Voriconazole, Sirolimus)
- •Has a known diagnosis of HIV, hepatitis B or hepatitis C
研究组 & 干预措施
Intervention
For 14 day study protocol, including five days of intervention with Belzutifan
干预措施: Belzutifan (Drug)
结局指标
主要结局
Tyrosine measurements
时间窗: Baseline, day 5 and day 14
The quantitative change in the amino acid tyrosine from baseline to the end of the study intervention (day 5) and to the end of the study (day 14).
次要结局
- Plasma metanephrine measurements(Baseline, day 5 and day 15)
研究者
Ruth Casey
Principal Investigator
Cambridge University Hospitals NHS Foundation Trust