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

Condition(s) targeted: Prostate Cancer

Intervention: tanespimycin (Drug); chemotherapy (Procedure)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Mayo Clinic

Official(s) and/or principal investigator(s):
Elisabeth I. Heath, MD, Study Chair, Affiliation: Barbara Ann Karmanos Cancer Institute

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.

Official title: A Phase II Trial of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) In Patients With Hormone-Refractory Metastatic Prostate Cancer

Study design: Treatment, Open Label

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

Secondary outcome:

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

Detailed description: 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 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.

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

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

- 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

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

Mayo Clinic Scottsdale, Scottsdale, Arizona 85259, United States

Howard University Cancer Center at Howard University Hospital, Washington, District of Columbia 20060, United States

Mayo Clinic - Jacksonville, Jacksonville, Florida 32224, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States

Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis, Missouri 63110, United States

University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792-6164, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: August 2005
Last updated: December 25, 2007