Ignite Creation Date:
2024-05-05 @ 11:36 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00088374
Status:
COMPLETED
Last Update Posted:
2012-07-27
First Post:
2004-07-23
Brief Title:
17AAG to Treat Kidney Tumors in Von Hippel-Lindau Disease
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase II Study of 17-Allylamino-17-Demethoxygeldanamycin in Patients With Von Hippel Lindau Disease and Renal Tumors
Status:
COMPLETED
Status Verified Date:
2012-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine whether the drug 17AAG 17-allylamino 17-demethoxygeldanamycin can shrink kidney tumors in patients with Von Hippel-Lindau disease VHL a rare inherited syndrome in which patients develop tumors in certain parts of the body 17AAG contributes to the destruction of proteins in cells that may play in role in causing cancer and spurring tumor growth The study will also look at the effect of 17AAG on other tumors patients may have that are caused by VHL on the amount of blood vessels in the tumors on the biologic activity of the tumor and on cells circulating in the bloodstream as well as the safety of the drug and its impact on the kidney tumor in patients whose tumors is removed
Patients 18 years of age and older with von Hippel-Lindau disease who have at least one kidney tumor large enough to pose a risk of metastasis spread of cancer to other parts of the body may be eligible for this study Candidates are screened with a medical history and physical examination computed tomography CT scan brain magnetic resonance imaging MRI see below and blood and urine tests Additional tests including a 24-hour urine collection ultrasound of the testicles in men hearing test eye exam and MRI of the spine may be done if recent test results are not available
Participants undergo the following tests and procedures
MRI This test uses a strong magnetic field and radio waves to show structural and chemical changes in tissue During the scan the patient lies on a table in a narrow cylinder containing a magnetic field wearing earplugs to muffle loud noises that occur with electrical switching of the magnetic fields A catheter plastic tube is inserted into the patients arm to administer a contrast dye that enhances the images
17AAG treatment Patients receive 17AAG infusions into a vein once a week for 3 weeks out of every 4 for 3 months The infusions last up to 1 to 2 hours
Repeat testing After 3 months patients have repeat MRI scans to measure changes in tumor activity blood flow and number of blood vessels in the tumor since the pretreatment scans They may have additional tests including a CT scan eye exam and other tests to evaluate the effect of 17AAG on the tumors
Patients 18 years of age and older with von Hippel-Lindau disease who have at least one kidney tumor large enough to pose a risk of metastasis spread of cancer to other parts of the body may be eligible for this study Candidates are screened with a medical history and physical examination computed tomography CT scan brain magnetic resonance imaging MRI see below and blood and urine tests Additional tests including a 24-hour urine collection ultrasound of the testicles in men hearing test eye exam and MRI of the spine may be done if recent test results are not available
Participants undergo the following tests and procedures
MRI This test uses a strong magnetic field and radio waves to show structural and chemical changes in tissue During the scan the patient lies on a table in a narrow cylinder containing a magnetic field wearing earplugs to muffle loud noises that occur with electrical switching of the magnetic fields A catheter plastic tube is inserted into the patients arm to administer a contrast dye that enhances the images
17AAG treatment Patients receive 17AAG infusions into a vein once a week for 3 weeks out of every 4 for 3 months The infusions last up to 1 to 2 hours
Repeat testing After 3 months patients have repeat MRI scans to measure changes in tumor activity blood flow and number of blood vessels in the tumor since the pretreatment scans They may have additional tests including a CT scan eye exam and other tests to evaluate the effect of 17AAG on the tumors
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 brain spine adrenal glands eyes and pancreas
The molecular hallmark of VHL is inactivation of the VHL gene which leads to accumulation of the hypoxia inducible factors HIF this in turn results in overexpression of several genes including vascular endothelial growth factor VEGF glucose transporter 1 GLUT-1 transforming growth factor alpha TGF-α platelet-derived growth factor PDGF and erythropoietin which play an important role in tumorigenesis tumor growth and metastasis
17-allylamino-17-demethoxygeldanamycin 17AAG is an inhibitor of the cellular chaperone heat shock protein 90 Hsp90 and its interaction with Hsp90 leads to destabilization and degradation of several proteins that depend on Hsp90 for their stability
The alpha subunit of HIF1 is one such Hsp90 client protein and is susceptible to VHL independent 17AAG-induced degradation
Objectives
To evaluate the efficacy of 17 AAG administered as a single agent in von Hippel Lindau patients with renal tumors The primary endpoint of the trial is response of renal tumors following 3 cycles of therapy
To study the safety and tolerability of 17 AAG To evaluate PD modulation of hsp90 and to explore the utility dynamic contrast enhanced MRI in evaluation of blood flow and metabolic changes in renal tumors before and during therapy
Eligibility
Adults with clinical diagnosis of von Hippel Lindau disease Presence of one or more localized renal tumors for which surgical resection would be considered the standard approach
Design
Patients will receive 17 AAG as an intravenous infusion at a dose of 300mgm2 on days 1 8 and 15 of 28 day cycles
The study will follow a two-stage MinMax phase II design and will accrue a maximum of 26 patients
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 brain spine adrenal glands eyes and pancreas
The molecular hallmark of VHL is inactivation of the VHL gene which leads to accumulation of the hypoxia inducible factors HIF this in turn results in overexpression of several genes including vascular endothelial growth factor VEGF glucose transporter 1 GLUT-1 transforming growth factor alpha TGF-α platelet-derived growth factor PDGF and erythropoietin which play an important role in tumorigenesis tumor growth and metastasis
17-allylamino-17-demethoxygeldanamycin 17AAG is an inhibitor of the cellular chaperone heat shock protein 90 Hsp90 and its interaction with Hsp90 leads to destabilization and degradation of several proteins that depend on Hsp90 for their stability
The alpha subunit of HIF1 is one such Hsp90 client protein and is susceptible to VHL independent 17AAG-induced degradation
Objectives
To evaluate the efficacy of 17 AAG administered as a single agent in von Hippel Lindau patients with renal tumors The primary endpoint of the trial is response of renal tumors following 3 cycles of therapy
To study the safety and tolerability of 17 AAG To evaluate PD modulation of hsp90 and to explore the utility dynamic contrast enhanced MRI in evaluation of blood flow and metabolic changes in renal tumors before and during therapy
Eligibility
Adults with clinical diagnosis of von Hippel Lindau disease Presence of one or more localized renal tumors for which surgical resection would be considered the standard approach
Design
Patients will receive 17 AAG as an intravenous infusion at a dose of 300mgm2 on days 1 8 and 15 of 28 day cycles
The study will follow a two-stage MinMax phase II design and will accrue a maximum of 26 patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 040238 | OTHER | Clinical Center CC National Institutes of HEalth NIH | None |
| 04-C-0238 | OTHER | None | None |