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

Alternate Title

17-AAG in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Previous Hormone Therapy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	MAYO-MC0453 NCI-6651, 6651, NCT00118092

Objectives

Primary

1. 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

1. Determine the overall survival and disease-free survival rate in patients treated with this drug.
2. Determine the safety profile of this drug in these patients.
3. Determine the duration of PSA response and PSA control in patients treated with this drug.
4. Determine the partial and complete response rates in patients with measurable disease treated with this drug.
5. 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.

Entry 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

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
• No prior radiotherapy field that included the heart (e.g., mantle)

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 concurrent medications that would prolong QTc
• No other concurrent antineoplastic agents
• Concurrent zoledronate for bone metastases or hypercalcemia allowed

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

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

• QTc < 450 msec for male patients
• LVEF > 40% by MUGA
• EF normal by MUGA if prior anthracycline therapy
• No congenital long QT syndrome
• No left bundle branch block
• Deep venous thrombosis or other clinically significant thromboembolic event within the past 6 months allowed provided patient is clinically stable on anticoagulation therapy
• No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• No myocardial infarction within the past year
• No cerebrovascular accident or transient ischemic attack within the past 6 months
• No New York Heart Association class III or IV congestive heart failure
• No poorly controlled angina
• No uncontrolled dysrhythmia or dysrhythmias requiring medication
• No active ischemic heart disease within the past 12 months
• No other significant cardiac disease

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

Expected Enrollment

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

Outcomes

Prostate-specific antigen (PSA) level response from baseline measured ≤ 7 days prior to study and then 4-6 weeks

Overall survival from time of registration to time of death
Disease-free survival from time of registration to documentation of disease progression
Safety profile as measured by occurrence of toxicity from registration until within 30 days of completion of treatment
Duration of PSA response and PSA control as measured by PSA level from time of documented PSA response or control until response changes
Partial and complete response rates as measured by RECIST every 8 weeks
Correlation of changes in expression levels of interleukin-6 (IL-6), maspin and NF-kappaB in serum and tissue at baseline, day 15, and at time of treatment failure
Correlation of biomarkers with cancer and treatment-related outcomes by expression levels of IL-6, maspin, and NF-kappaB in serum and tissue at baseline, day 15, and at time of treatment failure

Outline

This is a multicenter study.

Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 2-6 hours 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.

Heath EI, Hillman DW, Vaishampayan U, et al.: A phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer. Clin Cancer Res 14 (23): 7940-6, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Elisabeth Heath, MD, Protocol chair		Ph: 313-576-8715; 800-527-6266 Email: heathe@karmanos.org

Registry Information
Official Title		A Phase II Trial of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) In Patients With Hormone-Refractory Metastatic Prostate Cancer
Trial Start Date		2005-08-31
Trial Completion Date		2008-12-01
Registered in ClinicalTrials.gov		NCT00118092
Date Submitted to PDQ		2005-05-12
Information Last Verified		2006-08-15
NCI Grant/Contract Number		CM17104, CA15083

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