Clinical trial · Interventional
Real-World Effectiveness and Pharmacogenetics of Belzutifan in VHL Syndrome: The BELIEVE-VHL Trial
The BELIEVE-VHL Trial: A Real-world Longitudinal Study on Belzutifan's Effectiveness, Pharmacogenetics, and Pharmacoeconomics in Von Hippel-Lindau (VHL) Syndrome Using the HIF2α Inhibitor Belzutifan
NCT07167329CI-TRIAL-00094969BELIEVE-VHLrecruitingPhase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
The BELIEVE-VHL Trial is a prospective real-life study designed to evaluate the therapeutic effects, benefits, and adverse effects of belzutifan, as well as the timing of treatment response and disease progression in patients with von Hippel-Lindau (VHL) syndrome.
Conditions
Conditions (8)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Endolymphatic Sac Tumor | Endolymphatic Sac Tumor | ONTOLOGY_EXACT | 0.98 |
| Hemangioblastoma (HB) of the Central Nervous System (CNS) | — | UNRESOLVED | — |
| Pheochromocytoma/Paraganglioma | — | UNRESOLVED | — |
| PNET | Primitive Neuroectodermal Tumor | ALIAS | 0.90 |
| Retinal Angiomatous Proliferation | — | UNRESOLVED | — |
| Von Hippel Lindau | — | UNRESOLVED | — |
| Von Hippel Lindau-Deficient Clear Cell Renal Cell Carcinoma | — | UNRESOLVED | — |
| Von Hippel Lindau Disease | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Belzutifan | Drug | Belzutifan | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Oral Belzutifan (WELIREG™)
- description
- Patients with von Hippel-Lindau Syndrome presenting with lesions or neoplasms requiring treatment with oral Belzutifan (WELIREG™)
- interventionNames
- Drug: Belzutifan
Primary outcomes (1)
- measure
- Objective Tumor Response per RECIST 1.1
- timeFrame
- From enrollment and initiation of treatment until the earliest of either documented disease progression or death from any cause, with follow-up of up to 104 weeks.
- description
- Evaluation of target lesion size according to RECIST 1.1 criteria at baseline, weeks 12, 24, 52, and annually, up to 104 weeks. Imaging modalities will include MRI for solid tumors, 68Ga-DOTATATE PET for pancreatic neuroendocrine tumors (PNET), and retinal fluorescein angiography (FA) for retinal lesions. Unit of Measure: Percentage of participants with objective response.
Secondary outcomes (7)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 14 Years
Show eligibility criteria text
Inclusion Criteria: * Age ≥ 14 years. * Clinical or genetic confirmation of von Hippel-Lindau (VHL) syndrome. * Presence of measurable or progressive VHL-associated tumors, as defined by RECIST 1.1 or disease-specific imaging criteria. * ECOG performance status of 0-2. * Adequate bone marrow, hepatic, and renal function as defined by laboratory reference values. * Ability to swallow oral medication. * Provision of written informed consent prior to enrollment. Exclusion Criteria: * Age \< 14 years. * Absence of a confirmed diagnosis of von Hippel-Lindau (VHL) syndrome. * Presence of an active malignancy outside the VHL tumor spectrum within the past 3 years, except for adequately treated basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or other malignancies considered cured for \>2 years. * Known hypersensitivity or allergic reaction to belzutifan or any excipient in the formulation. * History of severe or uncontrolled cardiovascular disease, including but not limited to unstable angina, myocardial infarction within the past 6 months, congestive heart failure requiring treatment, or uncontrolled hypertension. * Active infectious diseases, including HIV, hepatitis B, or hepatitis C. * Immunosuppressed status, whether due to underlying disease or ongoing therapy. * History of significant bleeding disorders, including bleeding diathesis, thrombocytopenia, or coagulopathy. * Radiotherapy administered within 4 weeks prior to study enrollment. * Major surgical procedure, including for VHL-related tumors, within 4 weeks prior to study enrollment, or immediate need for surgical intervention for tumor management. * Malabsorption secondary to prior gastrointestinal surgery or active gastrointestinal disease. * Current use of concomitant medications known to interact with belzutifan and significantly alter its bioavailability. * Anticipated low adherence to or planned interruption of belzutifan therapy.
References
Publications (16)
- BACKGROUNDElse T, Jonasch E, Iliopoulos O, Beckermann KE, Narayan V, Maughan BL, Oudard S, Maranchie JK, Iversen AB, Goldberg CM, Fu W, Perini RF, Liu Y, Linehan WM, Srinivasan R. Belzutifan for von Hippel-Lindau Disease: Pancreatic Lesion Population of the Phase 2 LITESPARK-004 Study. Clin Cancer Res. 2024 May 1;30(9):1750-1757. doi: 10.1158/1078-0432.CCR-23-2592. PMID 38393723
- BACKGROUNDEriksson M, Lindstrom B. Validity of Antonovsky's sense of coherence scale: a systematic review. J Epidemiol Community Health. 2005 Jun;59(6):460-6. doi: 10.1136/jech.2003.018085. PMID 15911640
- BACKGROUNDBagattini AM, Camey SA, Miguel SR, Andrade MV, de Souza Noronha KVM, de C Teixeira MA, Lima AF, Santos M, Polanczyk CA, Cruz LN. Electronic Version of the EQ-5D Quality-of-Life Questionnaire: Adaptation to a Brazilian Population Sample. Value Health Reg Issues. 2018 Dec;17:88-93. doi: 10.1016/j.vhri.2017.11.002. Epub 2018 May 11. PMID 29754016
- BACKGROUNDJonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R; MK-6482-004 Investigators. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med. 2021 Nov 25;385(22):2036-2046. doi: 10.1056/NEJMoa2103425. PMID 34818478
- BACKGROUNDChoueiri TK, Bauer TM, Papadopoulos KP, Plimack ER, Merchan JR, McDermott DF, Michaelson MD, Appleman LJ, Thamake S, Perini RF, Zojwalla NJ, Jonasch E. Inhibition of hypoxia-inducible factor-2alpha in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med. 2021 May;27(5):802-805. doi: 10.1038/s41591-021-01324-7. Epub 2021 Apr 22. PMID 33888901
- BACKGROUNDVarshney N, Kebede AA, Owusu-Dapaah H, Lather J, Kaushik M, Bhullar JS. A Review of Von Hippel-Lindau Syndrome. J Kidney Cancer VHL. 2017 Aug 2;4(3):20-29. doi: 10.15586/jkcvhl.2017.88. eCollection 2017.