Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Von Hippel-Lindau Disease and Kidney Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	NCI-04-C-0238 6399, NCI-6399, NCT00089375

Special Category: NCI Web site featured trial

Objectives

Primary

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

Secondary

1. Determine the safety and tolerability of this drug in these patients.
2. 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.
3. Determine the effect of this drug on renal tumor vascular density, vascular flow, and permeability by dynamic contrast-enhanced MRI or CT scans in these patients.

Entry 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

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
• No prior chest radiation or radiotherapy that may have included the heart in the field

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 concurrent medications that prolong or may prolong QTc
• No other concurrent anticancer agents or therapies

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• 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

Cardiovascular

• Baseline cardiac symptoms < grade 2
• No significant cardiac disease within the past 12 months including any of the following:
  • New York Heart Association class III or IV heart failure
  • Uncontrolled dysrhythmias requiring medication
  • Active ischemic heart disease (e.g., myocardial infarction and poorly controlled angina)
• No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation, ≥ 3 beats in a row)
• No congenital long QT syndrome
• No left bundle branch block
• No QTc ≥ 450 msec for men and 470 msec for women
• No abnormal LVEF by MUGA
• No history of cardiac toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)

Pulmonary

• Baseline pulmonary symptoms < grade 2
• DLCO > 80%
• No symptomatic pulmonary disease requiring medication including any of the following:
  • Dyspnea
  • Dyspnea on exertion
  • Paroxysmal nocturnal dyspnea
  • Oxygen requirement and significant pulmonary disease (i.e., chronic obstructive or restrictive pulmonary disease)
  • Home oxygen use that meets Medicare criteria
• No history of pulmonary toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)

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

Expected Enrollment

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

Outcomes

Response of renal tumors after 3 courses of study therapy

Effect of 17-N-allylamino-17-demethoxygeldanamycin (17AAG) on nonrenal tumors

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Ramaprasad Srinivasan, MD, Protocol chair		Ph: 301-496-4916

Related Information

Featured trial article
Web site for additional information

Registry Information
Official Title		A Phase II Study Of 17-Allylamino-17-Demethoxygeldanamycin In Patients With Von Hippel Lindau Disease And Renal Tumors
Trial Start Date		2004-07-22
Trial Completion Date		2009-01-26
Registered in ClinicalTrials.gov		NCT00089375
Date Submitted to PDQ		2004-07-08
Information Last Verified		2009-01-18

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