NIH Clinical Research Studies

Protocol Number: 04-C-0238

Active Accrual, Protocols Recruiting New Patients

Title:
A Phase 2 Study of 17-Allylamino-17-Demethoxygeldanamycin in Patients with Von Hippel Lindau Disease and Renal Tumors
Number:
04-C-0238
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 a 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 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.

- Positron emission tomography (PET): Two types of PET scans may be done. One determines tumor activity by measuring the amount of sugar (glucose) the tumor absorbs, and the other measures tumor blood flow. For both studies, catheters are placed in a vein in each arm, one for giving a radioactive substance (a radiation-labeled sugar molecule for the tumor activity test and radiation-labeled water for the blood flow test), and the other for taking blood samples. The patient lies in the doughnut shaped scanner while images are obtained of various parts of the body where tumors are located.

- 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 and PET 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.

- Research blood draws: Blood samples are collected four times during the first week of treatment and then before each dose of 17AAG to determine the effects of the drug on blood counts, liver function, and other body functions, and to monitor safety.

Patients whose tumors shrink with 17AAG treatment may continue to receive the drug for another 12 weeks, followed by repeat MRI and PET scans. Those whose tumors do not shrunk or grow after 12 weeks on the study are asked to undergo surgery to remove the kidney tumors to reduce the chance of tumor spread.

Sponsoring Institute:
National Cancer Institute (NCI)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): None

Eligibility Criteria:
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.

Life expectancy greater 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/uL,

absolute neutrophil count greater than or equal to 1,500/micro L,

platelet count greater than or equal to 100,000/mirco L,

Hgb greater than10Gm/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 x ULN,

total bilirubin less than or equal to ULN (less than 3 x 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 (with the exception of 18-FDG and 15-H2O for PET imaging).

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 CYP3A4 substrates and inducers qualify for enrollment for this study.

Pregnant women are excluded from this study.

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.

Special Instructions: Currently Not Provided
Keywords:
Kidney Cancer
VHL
17 AAG
Chemotherapy
Recruitment Keywords:
Von Hippel Lindau Disease
VHL
Renal Tumor
Conditions:
Hippel-Lindau Disease
Kidney Cancer
Investigational Drug(s):
17 allylamino-17-demethoxygeldanamycin
18 FDG
[15-O] H2O
EPL diluent
Investigational Device(s):
None

Contacts:
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:
Linehan WM, et al. Identification of the von Hippel-Lindau (VHL) gene. Its role in renal cancer. JAMA. 1995 Feb 15;273(7):564-70. Review. No abstract available. PMID: 7837390

Clifford SC, Maher ER. Von Hippel-Lindau disease: clinical and molecular perspectives. Adv Cancer Res. 2001;82:85-105. Review. PMID: 11447766

Maher ER, Kaelin WG Jr. von Hippel-Lindau disease. Medicine (Baltimore). 1997 Nov;76(6):381-91. Review. PMID: 9413424

Active Accrual, Protocols Recruiting New Patients

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