RATIONALE: Drugs used in chemotherapy, such as 17-AAG, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well 17-AAG works in treating patients with metastatic prostate cancer that did not respond to previous hormone therapy.

Condition	Intervention	Phase
recurrent prostate cancer adenocarcinoma of the prostate stage IV prostate cancer	Drug: 17-N-allylamino-17-demethoxygeldanamycin  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the prostate-specific antigen (PSA) response in patients with hormone-refractory metastatic prostate cancer treated with 17-N-allylamino-17-demethoxygeldanamycin (17-AAG).

Secondary

• Determine the overall survival and disease-free survival rate in patients treated with this drug.
• Determine the safety profile of this drug in these patients.
• Determine the duration of PSA response and PSA control in patients treated with this drug.
• Determine the partial and complete response rates in patients with measurable disease treated with this drug.
• Correlate changes in expression levels of interleukin-6, maspin, and NF-kappaB in serum and tissue with cancer and treatment-related outcomes in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) receive 2 additional courses of treatment beyond documentation of CR.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 16-28 patients will be accrued for this study within 20 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate
• Metastatic disease
• Measurable or evaluable disease
• Prostate-specific antigen (PSA) ≥ 5 ng/mL OR new areas of bony metastases on bone scan are required for patients with no measurable disease
• Objective disease progression OR rising PSA despite receiving androgen deprivation therapy and undergoing antiandrogen withdrawal
• Patients with a rising PSA must have 2 successive elevations (measured ≥ 1 week apart)
• Must be castrate (testosterone < 50 ng/mL)
• Luteinizing hormone-releasing hormone agonist therapy must be continued during study participation to maintain castrate levels of testosterone
• Must have received 1 prior chemotherapy regimen for metastatic disease
• No known brain metastases requiring active therapy
• Previously treated asymptomatic brain metastases allowed

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8.0 g/dL

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT and/or SGPT ≤ 2.5 times ULN AND alkaline phosphatase normal OR
• Alkaline phosphatase ≤ 4 times ULN AND SGOT and/or SGPT normal

Renal

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

Cardiovascular

• None of the following conditions within the past 6 months:
• Myocardial infarction
• Severe/unstable angina
• Symptomatic congestive heart failure
• Cerebrovascular accident or transient ischemic attack
• Deep venous thrombosis or other clinically significant thromboembolic event allowed within the past 6 months provided patient is clinically stable on anticoagulation therapy

Pulmonary

• Pulmonary embolus allowed within the past 6 months provided patient is clinically stable on anticoagulation therapy

Other

• Fertile patients must use effective contraception
• Willing and able to provide blood samples
• No serious allergy (i.e., hypotension, dyspnea, anaphylaxis, or edema) to eggs
• No other concurrent malignancy or history of a curatively treated malignancy with a survival prognosis of < 5 years
• No known HIV positivity
• No active infection
• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• See Disease Characteristics
• At least 4 weeks since prior flutamide (6 weeks for bicalutamide or nilutamide)

Radiotherapy

• At least 28 days since prior radiotherapy

Surgery

• More than 6 months since prior coronary or peripheral artery bypass grafting

Other

• More than 28 days since prior investigational agents for prostate cancer
• No concurrent agents that interact with cytochrome P450 3A4
• No concurrent warfarin for anticoagulation
• Concurrent low molecular weight heparin injection allowed
• No other concurrent antineoplastic agents
• Concurrent zoledronate for bone metastases or hypercalcemia allowed

Please refer to this study by ClinicalTrials.gov identifier  NCT00118092

Arizona
      Mayo Clinic Scottsdale, Scottsdale,  Arizona,  85259,  United States; Recruiting
District of Columbia
      Howard University Cancer Center at Howard University Hospital, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Missouri
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-0001,  United States; Recruiting

Study chairs or principal investigators

Elisabeth I. Heath, MD,  Study Chair,  Barbara Ann Karmanos Cancer Institute   

Study ID Numbers:  CDR0000433492; MAYO-MC0453; NCI-6651; NCT00118092
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 8, 2005
ClinicalTrials.gov Identifier:  NCT00118092
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-07-26