This study is NOT currently recruiting participants.
Number
04-C-0238
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Children;Fetuses;Pregnant Women
Keywords
Kidney Cancer; VHL; 17AAG; Chemotherapy
Recruitment Keyword(s)
Von Hippel Lindau Disease; VHL; Renal Tumor
Condition(s)
VHL pancreatic neuroendocrine tumors; VHL; VHL retinal angiomas; VHL hemangioblastomas; VHL endolymphatic sac tumors
Investigational Drug(s)
17 allylamino-17-demethoxygeldanamycin (17-AAG)
Investigational Device(s)
None
Intervention(s)
Drug: 17 allylamino-17-demethoxygeldanamycin (17-AAG)
Supporting Site
National Cancer Institute
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 the 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 pre-treatment scans. They may have additional tests, including a CT scan, eye exam, and other tests to evaluate the effect of 17AAG on the tumors.
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INCLUSION CRITERIA: Patients must satisfy all the following inclusion criteria to be eligible for study enrollment. 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 ECOG 0-2. Patients must have normal organ and marrow function as defined below: 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 ULN or measured 24 hr. creatinine clearance greater than 60 ml/min, AST and ALT less than 1.0 times the ULN, total bilirubin less than or equal to ULN (less than 3 times the NL in patients with Gilbert s disease). Negative HbsAg, HIV-1 and nonreactive HCV. No history of serious intercurrent medical illness. At least four weeks from completion of any other 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 or investigator or protocol chair. Ability to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: 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 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 CYP3A4 potent inhibitors. Patients who are on CYP3Aa4 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. 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 QTc. Patients who have significant cardiac disease including Heart failure that meets New York Heart Association (NYHA) class III and IV definitions, uncontrolled dysrhythmias, dysrhythmias requiring anti-arrhythmic 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 (VT or VF, greater than or equal to 3 beats in a row), QTc greater than or equal to 450msec for men and 470 msec for women, or LVEF below lower limit of normal by MUGA. Patients with a history of prior chest radiation or radiation that potentially included the heart in the treatment field. Patients with congenital long QT syndrome. Patients with left bundle branch block. Patients with symptomatic pulmonary disease requiring medication, including the following: dyspnea, dyspnea on exertion, paroxysmal nocturnal dyspnea, oxygen requirement and significant pulmonary disease, including chronic obstructive/restrictive pulmonary disease, patients meeting Medicare criteria for home oxygen. DLCO less than or equal to 80%. Patients with a prior history of cardiac or pulmonary toxicity after receiving anthracyclines, such as doxorubicin, daunorubicin, mitoxantrone, bleomycin, or BCNU. Patients with greater than or equal to grade 2 baseline pulmonary or cardiac symptoms.
Patients must satisfy all the following inclusion criteria to be eligible for study enrollment.
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 ECOG 0-2.
Patients must have normal organ and marrow function as defined below: 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 ULN or measured 24 hr. creatinine clearance greater than 60 ml/min, AST and ALT less than 1.0 times the ULN, total bilirubin less than or equal to ULN (less than 3 times the NL in patients with Gilbert s disease).
Negative HbsAg, HIV-1 and nonreactive HCV.
No history of serious intercurrent medical illness.
At least four weeks from completion of any other 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 or investigator or protocol chair.
Ability to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
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 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 CYP3A4 potent inhibitors. Patients who are on CYP3Aa4 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.
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 QTc.
Patients who have significant cardiac disease including
Heart failure that meets New York Heart Association (NYHA) class III and IV definitions, uncontrolled dysrhythmias, dysrhythmias requiring anti-arrhythmic 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 (VT or VF, greater than or equal to 3 beats in a row), QTc greater than or equal to 450msec for men and 470 msec for women, or LVEF below lower limit of normal by MUGA.
Patients with a history of prior chest radiation or radiation that potentially included the heart in the treatment field.
Patients with congenital long QT syndrome.
Patients with left bundle branch block.
Patients with symptomatic pulmonary disease requiring medication, including the following: dyspnea, dyspnea on exertion, paroxysmal nocturnal dyspnea, oxygen requirement and significant pulmonary disease, including chronic obstructive/restrictive pulmonary disease, patients meeting Medicare criteria for home oxygen.
DLCO less than or equal to 80%.
Patients with a prior history of cardiac or pulmonary toxicity after receiving anthracyclines, such as doxorubicin, daunorubicin, mitoxantrone, bleomycin, or BCNU.
Patients with greater than or equal to grade 2 baseline pulmonary or cardiac symptoms.
Principal Investigator
Referral Contact
For more information: