17AAG to Treat Kidney Tumors in Von Hippel-Lindau Disease
A Phase II Study of 17-Allylamino-17-Demethoxygeldanamycin in Patients With Von Hippel Lindau Disease and Renal Tumors
2 other identifiers
interventional
9
1 country
1
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 tumor(s) 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 patient's 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jul 2004
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2004
CompletedFirst Submitted
Initial submission to the registry
July 23, 2004
CompletedFirst Posted
Study publicly available on registry
July 26, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2009
CompletedResults Posted
Study results publicly available
September 29, 2011
CompletedJuly 27, 2012
July 1, 2012
4.5 years
July 23, 2004
May 24, 2011
July 23, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants With a Renal Tumor Response
Response is defined as the number of patients who experience a disease response (complete response (CR) or partial response (PR) of renal tumors)per RECIST criteria. CR is the disappearance of all target lesions. PR is at least a 20% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. See the protocol Link module for the full criteria if desired.
12 weeks
Secondary Outcomes (5)
Number of Participants With a Non-renal Tumor Response
Baseline and 12 weeks
The Number of Participants With Adverse Events
1 yr, 364 days
The Number of Participants With HIF, HSP90, and HSP70 Modulation in Resected Tumor Tissue and/or Peripheral Blood Lymphocytes
Baseline and 12 weeks
Number of Patients in Whom Renal Tumors Could be Identified by Positron Emission Tomography (PET)Based on Fludeoxyglucose 18F (18FDG) Uptake
Baseline and at 12 weeks
Number of Participants With Flow Dynamics Measured by DCE MRI Within the Renal and Non-renal Tumor
Baseline and during therapy (12 weeks)
Study Arms (1)
Von Hippel-Lindau (VHL) associated renal tumors
EXPERIMENTALInterventions
17 allylamino-17-demethoxygeldanamycin (17 AAG) given intravenously at a dose of 300 mg/m2 on days 1,8 and 15 of 28 day cycles.
18FDG PET performed at baseline and 12 weeks after treatment. At each timepoint participants can receive 250mCi 0-15 water and 15 mCi F18-FDG.
\[15-0\] H20 performed at baseline and 12 weeks after treatment. At each time point participants can receive 250mCi 0-15 water and 15 mCi F18-FDG. The water scans were done as several intravenous injections for several scans but not over a total of 250 mCi.
17AAG is formulated with this diluent. Supplied in a 50 mL flint vial containing 48 mL of 2% egg phospholipids, and 5% dextrose in Water for Injection, USP. Patients with a history of serious allergic reactions to eggs should not receive this agent.
Eligibility Criteria
You may qualify if:
- 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.
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of 17 AAG in patients less than 18 years of age, children are excluded from this study.
- Life expectancy less than 3 months.
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-2.
- Patients must have normal organ and marrow function as defined below: white blood cells (WBC)count greater than or equal to 3,000/microliter, absolute neutrophil count greater than or equal to 1,500/microliter, platelet count greater than or equal to 100,000/microliter, Hgb greater than 10Gm/dl, serum creatinine less than or equal to 1.0 upper limit of normal (ULN) or measured 24 hour creatinine clearance greater than 60 ml/min,aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 1.0 times the ULN, total bilirubin less than or equal to ULN(less than 3 times the normal limit (NL) in patients with Gilbert's disease).
- Negative hepatitis B surface antigen (HbsAg), human immunodeficiency virus type 1 (HIV-1) and nonreactive hepatitis C virus (HCV).
- No history of serious intercurrent illness.
- At least four weeks from completion of any surgical or investigational therapy for von Hippel Lindau disease.
- Willingness to undergo resection of renal tumor at the time point defined in the protocol.
- All men and women of childbearing potential must use effective contraception as determined by the principal investigator or protocol chair.
- Ability to understand and the willingness to sign a written informed consent document.
You may not qualify if:
- Prior or concomitant non-von Hippel Lindau associated malignancy with the exception of adequately treated basal or squamous cell carcinoma of the skin or any other malignancy from which the patient has remained disease free for more than five years.
- Any renal tumor greater than 4cm in size.
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (to grade 1 or less toxicity according to Common Terminology Criteria for Adverse Events version 3.0 (CTCAE 3.0) due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- Patients with known metastatic renal cell cancer.
- Patients with a history of serious allergy to eggs.
- Concomitant therapy with cytochrome P450 3A4 (CYP3A4) potent inhibitors.
- Patients who are on CYP3A4 substrates and inducers qualify for enrollment for this study.
- Pregnant women are excluded from this study because 17 AAG has the potential for teratogenic or abortifacient effects, and no data regarding its safety in pregnant women is available. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 17 AAG, breastfeeding should be discontinued if the mother is treated with 17 AAG.
- Human immunodeficiency virus (HIV)-positive patients are excluded from the study because of unknown but potential pharmacokinetic interactions of anti-retroviral drugs with 17 AAG.
- Use of any medications that prolong or may prolong corrected QT interval (QTc).
- Patients who have significant cardiac disease including heart failure that meets New York Heart Association (NYHA)class III and IV definitions, uncontrolled dysrhythmias requiring anti-arhythmic drugs, or patients with active ischemic heart disease including myocardial infarction and poorly controlled angina within 12 months of study entry.
- Patients who have a history of serious ventricular arrhythmia (ventricular tachycardia (VT) or ventricular fibrillation (VF),greater than or equal to 3 beats in a row), QTc greater than or equal to 450msec for men and 470msec for women, or left ventricular ejection fraction (LVEF) below lower limit of normal by multi gated acquisition scan(MUGA).
- Patients with a history of prior chest radiation or radiation that potentially included the heart in the treatment field.
- Patients with congenital long Q wave, T wave (QT) syndrome.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Cancer Institute, National Institutes of Health
Bethesda, Maryland, 20892, United States
Related Publications (3)
Linehan WM, Lerman MI, Zbar B. Identification of the von Hippel-Lindau (VHL) gene. Its role in renal cancer. JAMA. 1995 Feb 15;273(7):564-70. No abstract available.
PMID: 7837390BACKGROUNDClifford SC, Maher ER. Von Hippel-Lindau disease: clinical and molecular perspectives. Adv Cancer Res. 2001;82:85-105. doi: 10.1016/s0065-230x(01)82003-0.
PMID: 11447766BACKGROUNDMaher ER, Kaelin WG Jr. von Hippel-Lindau disease. Medicine (Baltimore). 1997 Nov;76(6):381-91. doi: 10.1097/00005792-199711000-00001.
PMID: 9413424BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Study did not meet accrual.
Results Point of Contact
- Title
- William M. Linehan, M.D.
- Organization
- National Cancer Institute, National Institutes of Health
Study Officials
- PRINCIPAL INVESTIGATOR
William M Linehan, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
Study Record Dates
First Submitted
July 23, 2004
First Posted
July 26, 2004
Study Start
July 1, 2004
Primary Completion
January 1, 2009
Study Completion
January 1, 2009
Last Updated
July 27, 2012
Results First Posted
September 29, 2011
Record last verified: 2012-07