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Von Hippel LindauPhase 2BELIEVE-VHLNCT07167329

Real-World Effectiveness and Pharmacogenetics of Belzutifan in VHL Syndrome: The BELIEVE-VHL Trial

A Phase 2 study testing Belzutifan in people with Von Hippel Lindau and Von Hippel Lindau Disease, run by José Claudio Casali da Rocha at 1 site in Brazil.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 14 years and older
What is being tested?
Belzutifan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteBrazil
Study dates
1 Jan 2024to 1 Jan 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 14 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

José Claudio Casali da Rocha, Head of Oncogenetics contact

+55 41 98505 8585

casali.rocha@accamargo.org.br

José Reinaldo De Oliveira Junior contact

+55 31 99549 3678

j.junior@accamargo.org.br

Brazil1 site, 1 recruiting

  • AC Camargo Cancer Center

    São Paulo, São Paulo, 01509900

    Giovana Tardin Torrezan, Research Coordinator, +55 11 2189 5020 ext. 5020, cep_accamargo@accamargo.org.br

    Sandra Almeida, Administrative CEP, +55 11 2189 5020 ext. 5020, cep_accamargo@accamargo.org.br

    Recruiting

Other trials in Brazil

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVE:

To evaluate the therapeutic effects, benefits, and adverse effects associated with belzutifan treatment, as well as the timing of treatment response and/or disease progression.

SECONDARY OBJECTIVES

  1. To evaluate the association of host intrinsic factors with toxicity and treatment response in a Brazilian cohort of patients with von Hippel-Lindau syndrome treated with belzutifan.
  2. To assess hemoglobin and erythropoietin levels during the first six months of treatment, and to document the need for subcutaneous erythropoietin supplementation in patients who develop grade 2-3 anemia, fatigue, or hypoxia.
  3. To evaluate the potential impact of erythropoietin supplementation on tumor growth during belzutifan treatment.
  4. To assess health-related quality of life and patient perceptions regarding VHL syndrome using validated questionnaires and instruments.
  5. To conduct a pharmacoeconomic analysis in the cohort of patients with access to belzutifan, assessing its impact on healthcare costs compared to the natural history of the disease.
Being tested
Belzutifan
Keywords
Belzutifan, von Hippel-Lindau, Renal Cell Clear Carcinoma, Hemangioblastoma of Central Nervous System, Pharmacogenetics
Medical subject headings
von Hippel-Lindau Disease, Hemangioblastoma, Neuroectodermal Tumors, Primitive, Pheochromocytoma, Paraganglioma, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BelzutifanDrug

    Patients with Von Hippel-Lindau Syndrome presenting with lesions or neoplasms requiring treatment with oral Belzutifan.

Study groups in NCT07167329
Study groupRoleWhat they receive
Oral Belzutifan (WELIREG™)ExperimentalPatients with von Hippel-Lindau Syndrome presenting with lesions or neoplasms requiring treatment with oral Belzutifan (WELIREG™)
Receives: Drug: Belzutifan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Tumor Response per RECIST 1.1

    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.

    Measured: 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.

Secondary outcomes (7)

  1. Incidence of Anemia (per CTCAE v5.0)

    Number of participants developing grade ≥2 anemia during treatment with belzutifan, evaluated according to CTCAE version 5.0.

    Correlate hematologic outcomes with tumor response (RECIST 1.1) and lesion dynamics to identify potential predictive biomarkers.

    Unit of Measure: Percentage of participants.

    Measured: Baseline to 104 weeks

  2. Mean Hemoglobin Level Over Time

    Longitudinal change in hemoglobin levels (g/dL) at months 1, 3, 6, 12, and annually thereafter.

    Unit of Measure: g/dL.

    Measured: Baseline to 104 weeks.

  3. Erythropoietin Levels Over Time

    Longitudinal change in endogenous erythropoietin levels (mIU/mL) at months 1, 3, 6, 12, and annually thereafter.

    Unit of Measure: mIU/mL.

    Measured: Time Frame: Baseline to 104 weeks

  4. Requirement for Erythropoietin Supplementation

    Proportion of participants requiring subcutaneous erythropoietin supplementation for symptomatic or grade ≥3 anemia, including dose, frequency, and duration.

    Unit of Measure: Percentage of participants.

    Measured: Baseline to 104 weeks

  5. Blood Transfusion Requirement

    Number of participants requiring at least one blood transfusion during treatment with belzutifan.

    Unit of Measure: Percentage of participants.

    Measured: Baseline to 104 weeks

  6. Patient-Reported Quality of Life (EORTC QLQ-C30)

    Change in health-related quality of life scores measured by the EORTC QLQ-C30: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, version 3.0, at baseline, months 1, 3, 6, 12, and annually thereafter.

    It consists of 28 items evaluating symptom burden and functional status, each scored on a 4-point Likert scale (1 = "Not at all," 2 = "A little," 3 = "Quite a bit," 4 = "Very much"). In addition, two items assess overall health and overall quality of life, each rated on a 7-point scale (1 = "Very poor" to 7 = "Excellent") All treatment modifications-including interruptions, dose reductions, or discontinuations-will be recorded throughout the study.

    Unit of Measure: Score from 0 to 100 (higher score indicates better quality of life).

    Measured: Baseline to 24 months

  7. Pharmacoeconomic Evaluation of Belzutifan Therapy in Individuals with von Hippel-Lindau Syndrome

    The pharmacoeconomic analysis will be conducted in the same cohort of participants treated with belzutifan. Retrospective data on direct medical costs, expressed in Brazilian Reais (R$), will be collected, including expenses related to medications, surgical procedures, and hospital admissions. Indirect costs, particularly those related to productivity losses, will also be assessed and quantified as a percentage reduction compared with healthy employees or as hours/days lost due to illness or treatment-related absenteeism during the preceding five years. All cost data will be analyzed on a per-patient-per-month (PPPM) basis, stratified by defined time intervals. Cost-effectiveness will be evaluated by comparing healthcare costs before and after belzutifan initiation, accounting for changes in procedure frequency and overall resource utilization. Unit of Measure: Brazilian Reais (R$) per PPPM.

    Measured: Retrospective analysis of the 5 years prior to belzutifan initiation and prospective follow-up for up to 2 years after treatment initiation.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Sep 2025
  2. Study start1 Jan 2024
  3. Primary completion1 Feb 2026 (estimated)
  4. Study completion1 Jan 2030 (estimated)

Resources

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
The BELIEVE-VHL Trial is a prospective cohort study designed to evaluate the effectiveness and adverse effects of belzutifan in 100 patients with von Hippel-Lindau syndrome enrolled in a single intervention arm. The trial is structured as a basket trial, including all VHL-associated tumors, in patients aged 14 years or older and at any disease stage. The intervention consists of oral administration of belzutifan (Welireg) 120 mg once daily in patients with clinically or genetically confirmed VHL who are symptomatic or present with progressive tumors.
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07167329
Sponsor's protocol ID
ACCamargoCC
Acronym
BELIEVE-VHL
Status last verified
Sep 2025
First submitted
25 Jan 2025
Last updated
11 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The investigators plan to share anonymized clinical and laboratorial data, outcomes, side effects, pharmacogenomic information, and their correlation with treatment. This will enable collaboration with other researchers to combine findings and enhance statistical power.

Publications

  • Else 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.

    PubMed 38393723

  • Eriksson 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.

    PubMed 15911640

  • Bagattini 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.

    PubMed 29754016

  • Jonasch 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.

    PubMed 34818478

  • Choueiri 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.

    PubMed 33888901

  • Varshney 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.

    PubMed 28785532

  • Priesemann M, Davies KM, Perry LA, Drake WM, Chew SL, Monson JP, Savage MO, Johnston LB. Benefits of screening in von Hippel-Lindau disease--comparison of morbidity associated with initial tumours in affected parents and children. Horm Res. 2006;66(1):1-5. doi: 10.1159/000093008. Epub 2006 Apr 27.

    PubMed 16651847

  • Daniels AB, Tirosh A, Huntoon K, Mehta GU, Spiess PE, Friedman DL, Waguespack SG, Kilkelly JE, Rednam S, Pruthi S, Jonasch EA, Baum L, Chahoud J; International VHL Surveillance Guidelines Consortium. Guidelines for surveillance of patients with von Hippel-Lindau disease: Consensus statement of the International VHL Surveillance Guidelines Consortium and VHL Alliance. Cancer. 2023 Oct 1;129(19):2927-2940. doi: 10.1002/cncr.34896. Epub 2023 Jun 19. No abstract available.

    PubMed 37337409

  • Krauss T, Ferrara AM, Links TP, Wellner U, Bancos I, Kvachenyuk A, Villar Gomez de Las Heras K, Yukina MY, Petrov R, Bullivant G, von Duecker L, Jadhav S, Ploeckinger U, Welin S, Schalin-Jantti C, Gimm O, Pfeifer M, Ngeow J, Hasse-Lazar K, Sanso G, Qi X, Ugurlu MU, Diaz RE, Wohllk N, Peczkowska M, Aberle J, Lourenco DM Jr, Pereira MAA, Fragoso MCBV, Hoff AO, Almeida MQ, Violante AHD, Quidute ARP, Zhang Z, Recasens M, Diaz LR, Kunavisarut T, Wannachalee T, Sirinvaravong S, Jonasch E, Grozinsky-Glasberg S, Fraenkel M, Beltsevich D, Egorov VI, Bausch D, Schott M, Tiling N, Pennelli G, Zschiedrich S, Darr R, Ruf J, Denecke T, Link KH, Zovato S, von Dobschuetz E, Yaremchuk S, Amthauer H, Makay O, Patocs A, Walz MK, Huber TB, Seufert J, Hellman P, Kim RH, Kuchinskaya E, Schiavi F, Malinoc A, Reisch N, Jarzab B, Barontini M, Januszewicz A, Shah N, Young WF Jr, Opocher G, Eng C, Neumann HPH, Bausch B. Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors. Endocr Relat Cancer. 2018 Sep;25(9):783-793. doi: 10.1530/ERC-18-0100. Epub 2018 May 10.

    PubMed 29748190

  • Dallagnol TN, Da Cas E, Junior OR, Casali-da-Rocha JC. Comprehensive characterization and building of National Registry of von Hippel-Lindau disease in Brazil. Mol Genet Genomic Med. 2023 Apr;11(4):e2136. doi: 10.1002/mgg3.2136. Epub 2023 Jan 10.

    PubMed 36625343

  • Gomy I, Molfetta GA, de Andrade Barreto E, Ferreira CA, Zanette DL, Casali-da-Rocha JC, Silva WA Jr. Clinical and molecular characterization of Brazilian families with von Hippel-Lindau disease: a need for delineating genotype-phenotype correlation. Fam Cancer. 2010 Dec;9(4):635-42. doi: 10.1007/s10689-010-9357-2.

    PubMed 20567917

  • Maher ER, Yates JR, Harries R, Benjamin C, Harris R, Moore AT, Ferguson-Smith MA. Clinical features and natural history of von Hippel-Lindau disease. Q J Med. 1990 Nov;77(283):1151-63. doi: 10.1093/qjmed/77.2.1151.

    PubMed 2274658

  • Kim WY, Kaelin WG. Role of VHL gene mutation in human cancer. J Clin Oncol. 2004 Dec 15;22(24):4991-5004. doi: 10.1200/JCO.2004.05.061.

    PubMed 15611513

  • Rocha JC, Silva RL, Mendonca BB, Marui S, Simpson AJ, Camargo AA. High frequency of novel germline mutations in the VHL gene in the heterogeneous population of Brazil. J Med Genet. 2003 Mar;40(3):e31. doi: 10.1136/jmg.40.3.e31. No abstract available.

    PubMed 12624160

  • Choyke PL, Glenn GM, Walther MM, Patronas NJ, Linehan WM, Zbar B. von Hippel-Lindau disease: genetic, clinical, and imaging features. Radiology. 1995 Mar;194(3):629-42. doi: 10.1148/radiology.194.3.7862955.

    PubMed 7862955

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Belzutifan in people with Von Hippel Lindau and Von Hippel Lindau Disease, run by José Claudio Casali da Rocha at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact José Claudio Casali da Rocha, Head of Oncogenetics (+55 41 98505 8585, casali.rocha@accamargo.org.br), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Tumor Response per RECIST 1.1 (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07167329, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2025.

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