Visualizing Vascular Endothelial Growth Factor (VEGF) Producing Lesions in Von Hippel-Lindau Disease - Full Text View

Purpose

Von Hippel Lindau disease (VHLD) is an inherited syndrome characterized by vascular malformations, kidney cancer, adrenal gland and pancreas tumors. The VHL protein is not functional in the different disease associated lesions which results in production of high amounts of vascular endothelial growth factor (VEGF). Currently there are no clinical, radiographic or molecular markers that can predict the natural history of a given lesion. With 89Zr-bevacizumab positron emission tomography (PET) scanning, VEGF can be visualized and quantified.

The investigators hypothesize that 89Zr-bevacizumab PET imaging is a useful tool to predict the behaviour of disease associated lesions in patients with VHLD.

Adult patients with VHLD who have had routine magnetic resonance imaging (MRI) scans of central nervous system (CNS) and abdomen will undergo a 89Zr-bevacizumab PET scan. MRI will be repeated within 12 months.

Condition	Intervention
Von Hippel-Lindau Disease Hemangioblastoma Renal Cell Carcinoma Pheochromocytoma Pancreatic Neuroendocrine Tumor	Other: 89Zr bevacizumab PET scan


Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective
Official Title:	Visualizing VEGF Producing Lesions in Von Hippel-Lindau Disease

Resource links provided by NLM:

Genetics Home Reference related topics: hereditary paraganglioma-pheochromocytoma nonsyndromic paraganglioma von Hippel-Lindau syndrome

MedlinePlus related topics: Nuclear Scans Von Hippel-Lindau Disease

Drug Information available for: Bevacizumab

Genetic and Rare Diseases Information Center resources: Kidney Cancer Renal Cancer Carcinoid Tumor Pancreatic Neuroendocrine Tumor Von Hippel-Lindau Disease Pheochromocytoma Hemangioblastoma Capillary Hemangioblastoma Neuroepithelioma Paragangliomas 1 Carotid Body Tumor Pancreatic Cancer

U.S. FDA Resources

Further study details as provided by University Medical Center Groningen:

Primary Outcome Measures:

Detection rate of VHL associated lesions with 89Zr-bevacizumab PET scans in patients with VHLD [ Time Frame: An 89Zr-bevacizumab PET scan will be performed within 6 weeks after routine MRI CNS investigation, MRI will be repeated within 12 months. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progressive lesions within 12 months, defined as new lesions or lesions that show an increase in size of at least 5% of the longest diameter on MRI, or lesions that become symptomatic [ Time Frame: The baseline MRI scan will be compared with a follow-up MRI scan within 12 months ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Blood samples will be taken at day 1 and at the day of the MRI scan for analysis of VEGF pathway related biomarkers (such as plasma VEGF, PDGF, placental growth factor (PlGF), soluble VEGF receptors) and endothelial activation markers (such as Von Willebrand Factor (VWF), plasminogen activator inhibitor type 1 antigen (PAI-1), tissue-type plasminogen activator antigen (t-PA) and circulating endothelial cells (CECs)). DNA analysis for evaluation of polymorphisms in genes involved in angiogenesis is optional. In available biopsy or resection specimens, additional molecular staining of VEGF pathway related proteins will be performed (such as VEGF, VEGF receptors, HIF).


Enrollment:	22
Study Start Date:	September 2009
Study Completion Date:	November 2012
Primary Completion Date:	November 2012 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Von Hippel Lindau Adult patients with Von Hippel-Lindau disease	Other: 89Zr bevacizumab PET scan Patients will be injected intravenously with 37 MBq, protein dose 5 mg 89Zr-bevacizumab at day 0. PET scans will be done at day 4. Other Name: VEGF imaging

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Patients will be selected from a tertiary referral center for Von Hippel-Lindau disease.

Criteria

Inclusion Criteria:

clinically or genetically proven VHLD
at least 1 measurable, VHL associated lesion in the CNS
routine MRI of the CNS ≤ 6 weeks before inclusion
routine CT or MRI of upper abdomen ≤ 3 months before inclusion or planned ≤ 3 months after 89Zr-bevacizumab PET scan
age ≥ 18 years
written informed consent must be given according to good clinical practice (GCP), and local regulations

Exclusion Criteria:

pregnancy
any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol, those conditions should be discussed with the patient before registration in the trial

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00970970

Locations


Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9700 RB

Sponsors and Collaborators

University Medical Center Groningen

VHL Family Alliance

Investigators


Principal Investigator:	Sjoukje Oosting, MD	University Medical Center Groningen

More Information


Responsible Party:	S.F. Oosting, prinicipal investigator, University Medical Centre Groningen
ClinicalTrials.gov Identifier:	NCT00970970 History of Changes
Other Study ID Numbers:	METc2009.119
Study First Received:	September 2, 2009
Last Updated:	November 5, 2012
Health Authority:	Netherlands: Medical Ethics Review Committee (METC) Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Center Groningen:


Vascular endothelial growth factor von Hippel Lindau disease molecular imaging biomarker

Additional relevant MeSH terms:


Von Hippel-Lindau Disease Carcinoma, Renal Cell Neuroendocrine Tumors Carcinoid Tumor Pheochromocytoma Adenoma, Islet Cell Hemangioblastoma Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms	Neoplasms by Site Kidney Diseases Urologic Diseases Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Paraganglioma Adenoma Pancreatic Neoplasms Digestive System Neoplasms Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Neurocutaneous Syndromes

ClinicalTrials.gov processed this record on September 23, 2016

Visualizing Vascular Endothelial Growth Factor (VEGF) Producing Lesions in Von Hippel-Lindau Disease (VHLimage)