A Phase II Trial of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Patients With Hormone-Refractory Metastatic Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- tanespimycin
- Conditions
- Adenocarcinoma of the Prostate
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- PSA Response as Defined by the Recommendations of the Prostate-Specific Antigen Working Group
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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. 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.
Detailed Description
PRIMARY OBJECTIVES: I. 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 OBJECTIVES: I. Determine the overall survival and disease-free survival rate in patients treated with this drug. II. Determine the safety profile of this drug in these patients. III. Determine the duration of PSA response and PSA control in patients treated with this drug. IV. Determine the partial and complete response rates in patients with measurable disease treated with this drug. V. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (tanespimycin)
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.
Intervention: tanespimycin
Treatment (tanespimycin)
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.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
PSA Response as Defined by the Recommendations of the Prostate-Specific Antigen Working Group
Time Frame: Up to 1 year
Normalization: PSA ≤4.0 ng/ml. This must be confirmed by a second PSA value measured when patient returns in 4-6 weeks. This qualifies as a CR response. \> \> 50% decline: A 50% decline in PSA value from baseline which must be confirmed by a second PSA value measured when patient returns in 4-6 weeks later. This qualifies as a PR response.\> \> Progression: A 25% or greater increase over baseline and an increase in the PSA level by at least 5 ng/mL, which is confirmed by a second value obtained approximately one week later. In addition, radiographic scans are required to confirm that a disease progression is by PSA only.
Secondary Outcomes
- Proportion of Overall Responses(Up to 3 years)
- Disease-free Survival(From registration to documentation of disease progression, assessed up to 3 years)
- Overall Survival(From registration to death due to any cause, assessed up to 3 years)
- Duration of PSA Response and PSA Control(From PSA response to time of progression, assessed up to 1 year)