Real-world belzutifan outcomes and pharmacogenetics in von Hippel-Lindau syndrome

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

This study will test belzutifan in people aged 14 and older with VHL syndrome to see how well it controls VHL-associated tumors, what side effects occur, and how genetic factors affect response.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 14 Years and up
• Sex: All
• Sponsor: AC Camargo Cancer Center (Academic / other)
• Locations: 1 site (São Paulo, São Paulo)
• Trial ID: NCT07167329 on ClinicalTrials.gov

What this trial studies

This is a prospective, real-world Phase 2 interventional study of oral belzutifan at AC Camargo Cancer Center in São Paulo enrolling patients with clinical or genetic confirmation of von Hippel-Lindau syndrome and measurable or progressive VHL-associated tumors. Participants will receive belzutifan with systematic monitoring of tumor response timing, disease progression, and adverse events using RECIST 1.1 and disease-specific imaging criteria. The protocol includes pharmacogenetic testing to link host intrinsic factors with toxicity and treatment response, serial hemoglobin and erythropoietin measurements with prespecified management of anemia, and evaluation of whether erythropoietin supplementation affects tumor growth. Secondary outcomes include health-related quality of life measures and a pharmacoeconomic analysis comparing treated patients to the natural history of VHL disease in the cohort.

Who should consider this trial

Good fit: Ideal candidates are people aged 14 or older with a clinical or genetic diagnosis of VHL syndrome, measurable or progressive VHL-associated tumors, ECOG performance status 0–2, adequate organ function, and the ability to take oral medication and attend visits at the study center.

Not a fit: Patients without confirmed VHL, younger than 14, with recent active non-VHL malignancy, severe uncontrolled cardiovascular disease, or a known allergy to belzutifan are unlikely to benefit or be eligible for this protocol.

Why it matters

Potential benefit: If successful, the study could support belzutifan as an effective oral option for controlling VHL-related tumors and provide genetic and clinical markers to guide safer, more personalized use.

How similar studies have performed: Belzutifan (a HIF-2α inhibitor) has shown tumor responses in prior clinical trials and received approvals for VHL-associated RCC, but prospective real-world and pharmacogenetic data remain limited.

Eligibility criteria

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.

Where this trial is running

São Paulo, São Paulo

• AC Camargo Cancer Center — São Paulo, São Paulo, Brazil (Recruiting)

Study contacts

• Study coordinator: José Claudio Casali da Rocha, Head of Oncogenetics

Conditions Von Hippel Lindau; Von Hippel Lindau Disease; Von Hippel Lindau-Deficient Clear Cell Renal Cell Carcinoma; Hemangioblastoma of the Central Nervous System; PNET; Retinal Angiomatous Proliferation; Pheochromocytoma/Paraganglioma; Endolymphatic Sac Tumor