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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Objective Tumor Response per RECIST 1.1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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.
研究组 & 干预措施
Oral Belzutifan (WELIREG™)
Patients with von Hippel-Lindau Syndrome presenting with lesions or neoplasms requiring treatment with oral Belzutifan (WELIREG™)
干预措施: Belzutifan (Drug)
结局指标
主要结局
Objective Tumor Response per RECIST 1.1
时间窗: 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.
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.
次要结局
- Incidence of Anemia (per CTCAE v5.0)(Baseline to 104 weeks)
- Mean Hemoglobin Level Over Time(Baseline to 104 weeks.)
- Patient-Reported Quality of Life (EORTC QLQ-C30)(Baseline to 24 months)
- Erythropoietin Levels Over Time(Time Frame: Baseline to 104 weeks)
- Requirement for Erythropoietin Supplementation(Baseline to 104 weeks)
- Blood Transfusion Requirement(Baseline to 104 weeks)
- Pharmacoeconomic Evaluation of Belzutifan Therapy in Individuals with von Hippel-Lindau Syndrome(Retrospective analysis of the 5 years prior to belzutifan initiation and prospective follow-up for up to 2 years after treatment initiation.)
研究者
José Claudio Casali da Rocha
Head of Department of Oncogenetics
AC Camargo Cancer Center