Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage IV Prostate Cancer
Conditions
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.
Interventions
DRUGtanespimycin
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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 * Previously treated asymptomatic brain metastases allowed * Performance status - ECOG 0-2 * At least 12 weeks * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 8.0 g/dL * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * SGOT and/or SGPT ≤ 2.5 times ULN AND alkaline phosphatase normal * Alkaline phosphatase ≤ 4 times ULN AND SGOT and/or SGPT normal * Creatinine clearance ≥ 60 mL/min * Creatinine normal * 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 embolus allowed within the past 6 months provided patient is clinically stable on anticoagulation therapy * 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 * At least 4 weeks since prior flutamide (6 weeks for bicalutamide or nilutamide) * At least 28 days since prior radiotherapy * No prior radiotherapy field that included the heart (e.g., mantle) * More than 6 months since prior coronary or peripheral artery bypass grafting * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PSA Response as Defined by the Recommendations of the Prostate-Specific Antigen Working Group | 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
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Overall Responses | Up to 3 years | Confirmed response rate was defined using Response Evaluation Criteria In Solid Tumors (RECIST). A confirmed response is defined as a complete response (CR) or partial response (PR) observed on subsequent scans at least 4 weeks apart. Confirmed response rate was estimated by the number of successes divided by the total number of evaluable patients. Complete Response (CR) is defined as the disappearance of all target lesions. Partial Response (PR) is defined as a 30% decrease in sum of longest diameter of target lesions. The proportion of confirmed responses will be estimated by the number of patients with confirmed responses divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. |
| Overall Survival | From registration to death due to any cause, assessed up to 3 years | Overall survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. |
| Disease-free Survival | From registration to documentation of disease progression, assessed up to 3 years | Disease-free survival time is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had progressed at the time of their death. In patients who have achieved a PSA response, we will assess the time to PSA progression. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression on day 1 post-registration. The distribution of disease-free survival time will be estimated using the method of Kaplan-Meier. |
| Duration of PSA Response and PSA Control | From PSA response to time of progression, assessed up to 1 year | The distribution of this response duration will be estimated using the method of Kaplan-Meier. In patients whose PSA has declined from baseline by at least 30 %, duration of PSA response will be defined as the time from PSA response to time of progression. If a patient goes on to alternate therapy, they will be censored at the date they end treatment on this study. Duration of PSA Control is defined as the time from the date of the first 30% decline in PSA until an inflection point is identified. Inflection point is defined as the time to first consistent PSA increase, the point at which PSA began what becomes a continuous increase \> (retrospectively identified). The inflection point is the point at which disease control could assume to be lost. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Tanespimycin) Patients receive 300 mg/m\^2 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. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Tanespimycin) |
|---|---|
| Age, Continuous | 68 years |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 17 |
| serious Total, serious adverse events | 2 / 17 |
Outcome results
Primary
PSA Response as Defined by the Recommendations of the Prostate-Specific Antigen Working Group
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.
Time frame: Up to 1 year
Population: All 15 eligible patients that started treatment were evaluated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Tanespimycin) | PSA Response as Defined by the Recommendations of the Prostate-Specific Antigen Working Group | 0 participants |
Secondary
Disease-free Survival
Disease-free survival time is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had progressed at the time of their death. In patients who have achieved a PSA response, we will assess the time to PSA progression. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression on day 1 post-registration. The distribution of disease-free survival time will be estimated using the method of Kaplan-Meier.
Time frame: From registration to documentation of disease progression, assessed up to 3 years
Population: All 15 eligible patients that started treatment were evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Tanespimycin) | Disease-free Survival | 1.8 months |
Secondary
Duration of PSA Response and PSA Control
The distribution of this response duration will be estimated using the method of Kaplan-Meier. In patients whose PSA has declined from baseline by at least 30 %, duration of PSA response will be defined as the time from PSA response to time of progression. If a patient goes on to alternate therapy, they will be censored at the date they end treatment on this study. Duration of PSA Control is defined as the time from the date of the first 30% decline in PSA until an inflection point is identified. Inflection point is defined as the time to first consistent PSA increase, the point at which PSA began what becomes a continuous increase \> (retrospectively identified). The inflection point is the point at which disease control could assume to be lost.
Time frame: From PSA response to time of progression, assessed up to 1 year
Population: No participants with PSA response or PSA control.
Secondary
Overall Survival
Overall survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time frame: From registration to death due to any cause, assessed up to 3 years
Population: All 15 eligible patients that started treatment were evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Tanespimycin) | Overall Survival | 9.4 months |
Secondary
Proportion of Overall Responses
Confirmed response rate was defined using Response Evaluation Criteria In Solid Tumors (RECIST). A confirmed response is defined as a complete response (CR) or partial response (PR) observed on subsequent scans at least 4 weeks apart. Confirmed response rate was estimated by the number of successes divided by the total number of evaluable patients. Complete Response (CR) is defined as the disappearance of all target lesions. Partial Response (PR) is defined as a 30% decrease in sum of longest diameter of target lesions. The proportion of confirmed responses will be estimated by the number of patients with confirmed responses divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Time frame: Up to 3 years
Population: All 15 eligible patients that started treatment were evaluated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Tanespimycin) | Proportion of Overall Responses | 0 percentage of responses |