An Experimental Study of Belzutifan Impact on Catecholamine Metabolism

NCT07680205 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: A097464REC reference: 25/PR/1644
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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 catecholamine metabolism called tyrosine in patients before, during and after 5 days of taking Belzutifan 120mg daily.

Conditions

Pheochromocytoma and Paraganglioma (PPGL); Pheochromocytoma Malignant; Pheochromocytoma, Metastatic; Pheochromocytoma/Paraganglioma; Pheochromocytoma

Keywords

Belzutifan; catecholamine synthesis

Outcome Measures

Primary Outcomes (1)

• 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).

  Baseline, day 5 and day 14

Secondary Outcomes (1)

• Plasma metanephrine measurements

  Baseline, day 5 and day 15

Study Arms (1)

Intervention

EXPERIMENTAL

For 14 day study protocol, including five days of intervention with Belzutifan

Drug: Belzutifan

Interventions

Belzutifan DRUG

Belzutifan 120mg daily for 5 days

Intervention

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• University of Cambridge: collaborator

Study Sites (1)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

RECRUITING

Related Publications (9)

• 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.

  PMID: 24893135 BACKGROUND

• Tufton 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.

  PMID: 27761935 BACKGROUND

• Buffet 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.

  PMID: 32295730 BACKGROUND

• Winzeler 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.

  PMID: 34870338 BACKGROUND

• Winzeler B, Challis BG, Casey RT. Precision Medicine in Phaeochromocytoma and Paraganglioma. J Pers Med. 2021 Nov 22;11(11):1239. doi: 10.3390/jpm11111239.

  PMID: 34834591 BACKGROUND

• Nazari 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.

  PMID: 37944546 BACKGROUND

• Gruber 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.

  PMID: 33693908 BACKGROUND

• Casey 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.

  PMID: 29147570 BACKGROUND

• Alkaissi 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.

  PMID: 39442048 BACKGROUND

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma; Neoplasm Metastasis

Interventions

belzutifan

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ruth T Casey, MD PhD

  Cambridge University Hospital and University of Cambridge

  PRINCIPAL INVESTIGATOR

Central Study Contacts

August Palma Senior Research Nurse - Endocrinology

CONTACT

01223 217 848; august.palma@nhs.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Single-arm, pilot study with 12 patients

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: July 2, 2026
• Study Start: April 27, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 2, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)