Pheochromocytoma and Paraganglioma (PPGL)Phase 2NCT07680205
An Experimental Study of Belzutifan Impact on Catecholamine Metabolism
A Phase 2 study testing Belzutifan in people with Pheochromocytoma and Paraganglioma (PPGL) and Pheochromocytoma Malignant, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Pheochromocytoma and Paraganglioma (PPGL), Pheochromocytoma Malignant, Pheochromocytoma, Metastatic
- What is being tested?
- Belzutifan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 27 Apr 2026to Dec 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Cambridge University Hospitals NHS Foundation Trust
Cambridge, Cambridgeshire, CB2 0QQ
About this study
Official title: An Experimental Pilot Study to Investigate Changes in Catecholamine Synthesis and Metabolism in Patients With Molecularly Profiled Phaeochromocytoma and Paraganglioma Taking Belzutifan
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.
Read the detailed description
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.
Plasma tyrosine and metanephrines will be performed using specific published research methods (liquid chromatography mass spectroscopy) and a percentage reduction in catecholamine metabolites and a percentage increase in tyrosine will be calculated for every patient at the end of the 14-day protocol.
Safety measures will include monitoring of full blood count, liver function tests and by measuring blood pressure and heart rate at baseline and at day 1-7, day 10 and day 14 in all patients recruited to the study.
Any changes in blood pressure during the study protocol will be reviewed by the PI and all changes to existing medications will be performed by the PI and recorded.
All recruited patients will be interviewed daily from day 0 to day 7 and again on day 10 and day 14 and all symptoms reported will be recorded by the PI.
- Conditions
- Pheochromocytoma and Paraganglioma (PPGL), Pheochromocytoma Malignant, Pheochromocytoma, Metastatic, Pheochromocytoma/Paraganglioma, Pheochromocytoma
- Being tested
- Belzutifan
- Keywords
- Belzutifan, catecholamine synthesis
- Medical subject headings
- Pheochromocytoma, Paraganglioma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelzutifanDrug
Belzutifan 120mg daily for 5 days
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | For 14 day study protocol, including five days of intervention with Belzutifan Receives: Drug: Belzutifan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tyrosine measurements
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).
Measured: Baseline, day 5 and day 14
Secondary outcomes (1)
Plasma metanephrine measurements
Quantitative changes in serial plasma metanephrines measured at baseline, at the end of the study intervention (day 5) and at the end of the study (day 14).
Measured: Baseline, day 5 and day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2026
- Study start27 Apr 2026
- Primary completionApr 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Pheochromocytoma and Paraganglioma (PPGL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-arm, pilot study with 12 patients
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Cambridge
- Responsible party
- Principal investigator, Ruth Casey, Cambridge University Hospitals NHS Foundation Trust
- Investigators
- Ruth T Casey, MD PhD, Principal investigator, Cambridge University Hospital and University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07680205
- Sponsor's protocol ID
- A097464
- Other IDs
- REC reference: 25/PR/1644
- Status last verified
- Jun 2026
- First submitted
- 23 Jun 2026
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, Naruse M, Pacak K, Young WF Jr; Endocrine Society. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Jun;99(6):1915-42. doi: 10.1210/jc.2014-1498.
PubMed 24893135Tufton N, Gunganah K, Hussain S, Druce M, Carpenter R, Ashby M, Drake WM, Akker SA. Alpha blockade-not to be underdone. Clin Endocrinol (Oxf). 2017 Feb;86(2):306-308. doi: 10.1111/cen.13262. Epub 2016 Nov 21. No abstract available.
PubMed 27761935Buffet A, Burnichon N, Favier J, Gimenez-Roqueplo AP. An overview of 20 years of genetic studies in pheochromocytoma and paraganglioma. Best Pract Res Clin Endocrinol Metab. 2020 Mar;34(2):101416. doi: 10.1016/j.beem.2020.101416. Epub 2020 Mar 10.
PubMed 32295730Winzeler B, Tufton N, S Lim E, Challis BG, Park SM, Izatt L, Carroll PV, Velusamy A, Hulse T, Whitelaw BC, Martin E, Rodger F, Maranian M, Clark GR, A Akker S, Maher ER, Casey RT. Investigating the role of somatic sequencing platforms for phaeochromocytoma and paraganglioma in a large UK cohort. Clin Endocrinol (Oxf). 2022 Oct;97(4):448-459. doi: 10.1111/cen.14639. Epub 2021 Dec 6.
PubMed 34870338Winzeler B, Challis BG, Casey RT. Precision Medicine in Phaeochromocytoma and Paraganglioma. J Pers Med. 2021 Nov 22;11(11):1239. doi: 10.3390/jpm11111239.
PubMed 34834591Nazari MA, Hasan R, Haigney M, Maghsoudi A, Lenders JWM, Carey RM, Pacak K. Catecholamine-induced hypertensive crises: current insights and management. Lancet Diabetes Endocrinol. 2023 Dec;11(12):942-954. doi: 10.1016/S2213-8587(23)00256-5. Epub 2023 Nov 6.
PubMed 37944546Gruber LM, Jasim S, Ducharme-Smith A, Weingarten T, Young WF, Bancos I. The Role for Metyrosine in the Treatment of Patients With Pheochromocytoma and Paraganglioma. J Clin Endocrinol Metab. 2021 May 13;106(6):e2393-e2401. doi: 10.1210/clinem/dgab130.
PubMed 33693908Casey RT, Challis BG, Pitfield D, Mahroof RM, Jamieson N, Bhagra CJ, Vuylsteke A, Pettit SJ, Chatterjee KC. Management of an acute catecholamine-induced cardiomyopathy and circulatory collapse: a multidisciplinary approach. Endocrinol Diabetes Metab Case Rep. 2017 Nov 9;2017:17-0122. doi: 10.1530/EDM-17-0122. eCollection 2017.
PubMed 29147570Alkaissi H, Nazari MA, Hadrava Vanova K, Uher O, Gordon CM, Talvacchio S, Diachenko N, Mukvich O, Wang H, Glod J, Zhuang Z, Pacak K. Rapid Cardiovascular Response to Belzutifan in HIF2A-Mediated Paraganglioma. N Engl J Med. 2024 Oct 24;391(16):1552-1555. doi: 10.1056/NEJMc2409427. No abstract available.
PubMed 39442048