RATIONALE: Chemotherapy drugs such as 17-N-allylamino-17-demethoxygeldanamycin work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of 17-N-allylamino-17-demethoxygeldanamycin in treating patients who have von Hippel-Lindau disease and kidney cancer.

Condition	Treatment or Intervention	Phase
stage I renal cell cancer von Hippel-Lindau Syndrome	Drug: 17-N-allylamino-17-demethoxygeldanamycin  Procedure: chemotherapy	Phase II

OBJECTIVES: Primary

• Determine the activity of 17-N-allylamino-17-demethoxygeldanamycin against renal tumors in patients with von Hippel-Lindau disease.

Secondary

• Determine the safety and tolerability of this drug in these patients.
• Determine the effect of this drug on non-renal tumors (e.g., pancreatic tumors, pheochromocytoma, retinal angiomas, or CNS hemangioblastomas) associated with von Hippel-Lindau disease.
• Determine the effect of this drug on renal tumor vascular density, vascular flow, and permeability by dynamic contrast-enhanced MRI in these patients.

OUTLINE: Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 28 days for 3 courses in the absence of unacceptable toxicity. Patients are evaluated for response after the third course. Patients with progressive or stable disease or whose renal tumor(s) is ≥ 3 cm undergo surgical resection of their tumor(s) off study. Patients with complete or partial response and whose renal tumor(s) is < 3 cm receive 3 additional courses of 17-AAG as above in the absence of unacceptable toxicity.

PROJECTED ACCRUAL: A total of 16-25 patients will be accrued for this study within 2-3 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Clinical diagnosis of von Hippel-Lindau (VHL) disease
• One or more localized renal tumors
• Candidate for surgical resection as standard therapy
• Tumor no larger than 4 cm
• No known metastatic renal cell cancer

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin > 10 g/dL

Hepatic

• AST and ALT normal
• Bilirubin normal (< 3 times upper limit of normal for patients with Gilbert's disease)
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative

Renal

• Creatinine normal OR
• Creatinine clearance > 60 mL/min

Other

• No history of serious allergy to eggs
• No non-VHL-associated malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer
• No other serious medical illness
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered

Surgery

• At least 4 weeks since prior surgery for VHL disease

Other

• At least 4 weeks since prior investigational therapy for VHL disease
• No other concurrent investigational therapy
• No concurrent CYP3A4 inhibitors, including any of the following:
• Clotrimazole
• Ketoconazole
• Troleandomycin
• Cyclosporine
• Itraconazole
• Erythromycin
• Clarithromycin
• Nefazodone
• Grapefruit juice
• HIV protease inhibitors (e.g., indinavir, nelfinavir, ritonavir, or saquinavir)
• No other concurrent anticancer agents or therapies

Maryland
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting

Study chairs or principal investigators

Ramaprasad Srinivasan, MD,  Study Chair,  NCI - Urologic Oncology Branch   

Study ID Numbers:  CDR0000378309; NCI-04-C-0238; NCI-6399
Record last reviewed:  September 2004
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00089375
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-29