Overview
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.
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
- 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.
- 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.
- To evaluate the potential impact of erythropoietin supplementation on tumor growth during belzutifan treatment.
- To assess health-related quality of life and patient perceptions regarding VHL syndrome using validated questionnaires and instruments.
- 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.
Eligibility
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.