A Phase 2 Study of ZD6474 (Vandetanib) in Patients With Von Hippel Lindau Disease and Renal Tumors
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Overall Response Rate.
Study Overview
Brief Summary
This study will examine the effectiveness of an investigational drug called ZD6474 (also known as vandetanib or ZACTIMA). Vandetanib is an experimental drug that is designed to prevent the growth and development of new blood vessels on tumors and to prevent the direct growth of cancer cells. It has been tested in a number of clinical trials on adults with cancer, but the United States (U.S.) Food and Drug Administration has not specifically approved it as a cancer treatment. The purpose of this investigational study is to better understand how vandetanib affects humans who have kidney cancer related to von Hippel-Lindau (VHL) disease, and to develop tests that may improve researchers understanding of kidney cancer and its effects.
Volunteers must be at least 18 years old and must have been diagnosed with kidney cancer related to VHL. Candidates must have a life expectancy greater than three months and must have at least one measurable renal tumor for study purposes. Candidates may not be receiving any other investigational agents or have been treated with an investigational drug within the past four weeks. Candidates who have had surgery, chemotherapy, or radiotherapy within the past four weeks will be excluded from the study. Candidates will be screened with a physical examination and medical history.
During the study, participants will receive an oral dose of vandetanib once a day for 28 days (a treatment period known as a cycle). Participants will need to return to the National Institutes of Health every two weeks on the same day of the week as the first dose of vandetanib for a series of tests and procedures, including blood and urine tests and an electrocardiogram. Every 12 weeks, computerized tomography (CT) or magnetic resonance imaging (MRI) scans will be done to assess the size of participants tumors. Participants whose tumors do not grow and who do not have unacceptable side effects may continue to receive vandetanib to maintain the current condition, until researchers conclude the study....
Detailed Description
Background:
Von Hippel Lindau disease is a hereditary cancer syndrome in which affected individuals are at risk for developing tumors in a number of organs, including the kidneys, brain, spine, adrenal glands, eyes and pancreas.
The molecular hallmark of VHL is inactivation of the VHL gene which leads to accumulation of proteins targeted for degradation through the ubiquitin pathway, which includes a group of transcriptionally active proteins called the hypoxia inducible factors (HIF), whose alpha subunits undergo degradation in a VHL-dependent fashion. Accumulation of HIFs results in overexpression of several genes including vascular endothelial growth factor (VEGF), glucose transporter 1 (GLUT-1), transforming growth factor (TGF)-alpha, platelet- derived growth factor (PDGF), and erythropoietin, which are believed to play a role in tumorigenesis, tumor progression and metastasis.
ZD6474 is an orally administered receptor tyrosine kinase inhibitor with activity against the Kinase insert domain-containing receptor/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) and the epidermal growth factor receptor (EGFR). Kinase insert domain receptor (KDR)/vascular growth factor receptor 2 (VEGFR2) is an endothelial cell receptor for vascular endothelial growth factor (VEGF) and plays a crucial role in mediating tumor angiogenesis, while epidermal growth factor receptor (EGFR) (a receptor for TGF-alpha and epidermal growth factor (EGF) is believed to mediate tumor growth and proliferation.
Objective:
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 100 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Vandetanib in Participants with Kidney Cancer
300 mg/day (starting dose) oral dose of vandetanib once a day for 28 days
Intervention: ZACTIMA (Vandetanib) (ZD6474) (Drug)
Outcomes
Primary Outcomes
Overall Response Rate.
Time Frame: Baseline and every 3 cycles, up to 2 years
Overall response rate is defined as the percentage of participants with either a partial or complete response occurring at any time after initiation of therapy. Response is determined by the Response Evaluation Criteria in Solid Tumors (RECIST). Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Complete response (CR) is a disappearance of all target lesions. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (progressive disease), taking as reference the smallest sum LD since the treatment started.
Secondary Outcomes
- Response in Pancreatic Tumors/Cysts Associated With Von Hippel Lindau (VHL)(Baseline and every 3 cycles while on study, up to 2 years.)
- Time To Progression (TTP)(Baseline and every 3 cycles while on study, up to 2 years.)
- Progression Free Survival (PFS)(Baseline and every 3 cycles while on study, up to 2 years.)
- Effect of Vandetanib (ZD6474) on Endothelial Progenitor Cells(Pre treatment, 4 hours after first treatment, and after one cycle of treatment (one cycle = 28 days))
- Effect of Vandetanib (ZD6474) on Circulating Endothelial Cells (CEC)(Pre treatment, 4 hours after first treatment, and after one cycle of treatment (one cycle = 28 days))
- Number of Participants With Adverse Events(72 months and 14 days)
- Response in Central Nervous System (CNS) Hemangioblastomas Associated With Von Hippel Lindau (VHL)(Baseline and every 3 cycles while on study, up to 2 years.)
- Response in Pheochromocytomas Associated With Von Hippel Lindau (VHL)(Baseline and every 3 cycles while on study, up to 2 years.)
Investigators
W. Marston Linehan, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)