Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage IV Prostate Cancer
Conditions
Brief summary
Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop tumor cells from dividing so they stop growing or die. This phase II trial is studying how well ixabepilone works in treating patients with metastatic prostate cancer that has not responded to previous hormone therapy.
Detailed description
PRIMARY OBJECTIVE: I. To determine the effect on percent with a 50% decrease in PSA response in patients with metastatic prostate cancer who have progressed on androgen ablation therapy and are classified into 1 of 3 separate categories: 1. Never received prior chemotherapy/cytotoxic therapy 2. Received prior taxane-based regimen 3. Received 2 prior cytotoxic chemotherapy regimens (including, but not limited to, prior taxane and anthracyclines) SECONDARY OBJECTIVES: I. Determine measurable disease response in patients with measurable disease treated with this drug and overall response rate. II. Determine the toxic effects of this drug in these patients. III. Determine the duration of PSA and measurable disease response in patients treated with this drug. IV. Determine the expression of p53, multidrug resistance protein, and Bcl-2 by immunohistochemistry in the primary tumors of patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (none vs 1 prior taxane-containing regimen vs 2 prior cytotoxic regimens). Patients receive ixabepilone IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 3 years.
Interventions
DRUGixabepilone
Given IV
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 * Evidence of disease progression (e.g., new lesions on bone scan or new/enlarging lesions on CT scan) OR rising prostate-specific antigen (PSA) within the past 4 weeks * Radiologic evidence of hydronephrosis alone is not considered evidence of metastatic disease (e.g., increasing PSA) * Patients with bone metastases only (i.e., lacking soft tissue disease) must have a PSA level \>= 10 ng/mL within the past week * Patients with stable disease and rising PSA must show 2 consecutive rises in PSA measurements taken at least 2 weeks apart * Most recent PSA level must be obtained within the past 4 weeks * Disease progression after prior anti-androgen withdrawal must be confirmed by a rising PSA after the 4-6 week washout period (e.g., PSA level higher than the last PSA obtained while on anti-androgen therapy) * Failed prior bilateral orchiectomy or other primary hormonal therapy * Patients who have not undergone bilateral orchiectomy must continue on luteinizing hormone-releasing hormone (LHRH) agonist therapy (e.g., leuprolide or goserelin) or LHRH antagonist (e.g., abarelix) during study treatment AND must have a serum testosterone level =\< 50 ng/dL within the past 4 weeks to confirm androgen suppression * ECOG 0-2 * Granulocyte count \>= 1,500/mm\^3 * Platelet count \>= 100,000/mm\^3 * WBC \>= 4,000/mm\^3 * SGPT =\< 2 times upper limit of normal * Bilirubin =\< 1.5 mg/dL * INR normal * Creatinine =\< 1.5 mg/dL * Creatinine clearance \>= 50 mL/min * No New York Heart Association class III-IV heart disease * No myocardial infarction within the past 6 months * No active angina pectoris * No evidence of ventricular dysrhythmias or other unstable arrhythmia * Rate-controlled atrial fibrillation allowed provided the patient is asymptomatic * No other malignancy within the past 5 years except curatively treated nonmelanoma skin cancer * No serious medical illness or active infection that would preclude study participation * No concurrent prophylactic filgrastim (G-CSF) * No more than 2 prior cytotoxic chemotherapy regimens for hormone-refractory disease * At least 4 weeks since prior chemotherapy with a taxane-based regimen, mixantrone, or another cytotoxic chemotherapy regimen provided there is evidence of progressive disease * At least 4 weeks since prior flutamide AND continued evidence of progressive disease * At least 6 weeks since prior bicalutamide or nilutamide AND continued evidence of progressive disease * At least 4 weeks since prior estrogen or estrogen-like agents (e.g., PC-SPES, saw palmetto, or other herbal products which may contain phytoestrogens) * At least 4 weeks since prior hormonal therapy, including megestrol, finasteride, ketoconazole, or systemic corticosteroids * No concurrent estrogen or estrogen-like agents (e.g., PC-SPES, saw palmetto, or other herbal products which may contain phytoestrogens) * More than 4 weeks since prior radiotherapy * No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium * No other prior radioisotope * No concurrent radiotherapy for pain control * No more than 1 prior experimental (non-cytotoxic) therapy AND evidence of progressive disease * At least 4 weeks since prior experimental therapy * Concurrent bisphosphonates (e.g., pamidronate or zoledronate) allowed provided treatment was initiated at least 4 weeks ago and there is evidence of progressive disease * No other concurrent investigational agents * No concurrent therapeutic warfarin * Concurrent prophylactic or therapeutic doses of low molecular weight heparin allowed provided criterion for INR is met * No carcinomatous meningitis or brain metastases * Fertile patients must use effective contraception * No peripheral neuropathy \> grade 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With PSA Response | Every 4 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry | PSA response is defined as a decline from baseline value by \>=50%, or normalization of PSA (PSA \< 0.2 ng/lm), confirmed by a second measurement \>= 4 weeks later. The proportion of patients with PSA response was reported separately for 3 strata. Additional patients accrued to this study were not included in this analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Measurable Disease Response (Best Overall Response) | Every 8 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry | Only patients with measurable disease were included in this analysis. The proportion of patients with measurable disease response (based on RECIST: Response Evaluation Criteria in Solid Tumors) was reported separately for 3 strata. Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR |
| Duration of PSA Response | Every 4 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry | Duration of PSA response was defined as the time from the date of onset of PSA response until the date the criteria were met for PSA progression. Only patients with a PSA response were included in this analysis. The results were reported separately for 3 strata. |
| Duration of Measurable Disease Response | Every 8 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry | Duration of measurable disease response was defined as the time from the date when measurement criteria were met for complete or partial response, whichever status was recorded first, until the first date that recurrent or progressive disease was objectively documented based on RECIST (Response Evaluation Criteria in Solid Tumors). Only patients with measurable disease response were included in this analysis. |
Countries
United States
Participant flow
Recruitment details
The study was activated on September 16, 2004 and terminated on February 4, 2009 after reaching its accrual goal. A total of 124 patients were recruited from ECOG member institutions.
Participants by arm
| Arm | Count |
|---|---|
| Ixabepilone - no Prior Chemo All patients on this study received the same treatment but were categorized into 3 strata, including the no prior chemo stratum, the prior taxane stratum, and two prior chemo stratum. Only eligible and treated patients are included in the analysis. | 35 |
| Ixabepilone - Prior Taxane All patients on this study received the same treatment but were categorized into 3 strata, including the no prior chemo stratum, the prior taxane stratum, and two prior chemo stratum. Only eligible and treated patients are included in the analysis. | 42 |
| Ixabepilone - Two Prior Chemo All patients on this study received the same treatment but were categorized into 3 strata, including the no prior chemo stratum, the prior taxane stratum, and two prior chemo stratum. Only eligible and treated patients are included in the analysis. | 32 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 18 | 17 | 13 |
| Overall Study | Death | 2 | 1 | 0 |
| Overall Study | Disease progression | 9 | 19 | 12 |
| Overall Study | Extradural disease | 0 | 0 | 1 |
| Overall Study | Ineligible | 4 | 7 | 4 |
| Overall Study | Physician Decision | 1 | 1 | 1 |
| Overall Study | Response achieved | 0 | 1 | 0 |
| Overall Study | Symptomatic deterioration | 1 | 1 | 3 |
| Overall Study | Use of coumadin | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 2 |
Baseline characteristics
| Characteristic | Ixabepilone - no Prior Chemo | Ixabepilone - Prior Taxane | Ixabepilone - Two Prior Chemo | Total |
|---|---|---|---|---|
| Age, Continuous | 72 years | 69 years | 67.5 years | 70 years |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 35 Participants | 42 Participants | 32 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 122 / 123 |
| serious Total, serious adverse events | 90 / 123 |
Outcome results
Primary
Proportion of Patients With PSA Response
PSA response is defined as a decline from baseline value by \>=50%, or normalization of PSA (PSA \< 0.2 ng/lm), confirmed by a second measurement \>= 4 weeks later. The proportion of patients with PSA response was reported separately for 3 strata. Additional patients accrued to this study were not included in this analysis.
Time frame: Every 4 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry
Population: If the regimen demonstrated a PSA response rate specified in the protocol, additional patients would be entered so the total number of eligible patients with measurable disease in each stratum is 25. But the PSA response rate was only calculated among the first cohort of patients, not including the additional patients with measurable disease.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixabepilone - no Prior Chemo | Proportion of Patients With PSA Response | 0.33 Proportion of participants |
| Ixabepilone - Prior Taxane | Proportion of Patients With PSA Response | 0.24 Proportion of participants |
| Ixabepilone - Two Prior Chemo | Proportion of Patients With PSA Response | 0.18 Proportion of participants |
Secondary
Duration of Measurable Disease Response
Duration of measurable disease response was defined as the time from the date when measurement criteria were met for complete or partial response, whichever status was recorded first, until the first date that recurrent or progressive disease was objectively documented based on RECIST (Response Evaluation Criteria in Solid Tumors). Only patients with measurable disease response were included in this analysis.
Time frame: Every 8 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry
Population: Only patients with measurable disease response were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone - no Prior Chemo | Duration of Measurable Disease Response | 5.1 Months |
| Ixabepilone - Prior Taxane | Duration of Measurable Disease Response | 3.7 Months |
Secondary
Duration of PSA Response
Duration of PSA response was defined as the time from the date of onset of PSA response until the date the criteria were met for PSA progression. Only patients with a PSA response were included in this analysis. The results were reported separately for 3 strata.
Time frame: Every 4 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry
Population: If the regimen demonstrated a PSA response rate specified in the protocol, additional patients would be entered so the total number of eligible patients with measurable disease in each stratum is 25. But the PSA response related analysis was only done among the first cohort of patients, not including the additional patients with measurable disease.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone - no Prior Chemo | Duration of PSA Response | 6.0 Months |
| Ixabepilone - Prior Taxane | Duration of PSA Response | 7.6 Months |
| Ixabepilone - Two Prior Chemo | Duration of PSA Response | NA Months |
Secondary
Proportion of Patients With Measurable Disease Response (Best Overall Response)
Only patients with measurable disease were included in this analysis. The proportion of patients with measurable disease response (based on RECIST: Response Evaluation Criteria in Solid Tumors) was reported separately for 3 strata. Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR
Time frame: Every 8 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry
Population: Only patients with measurable disease were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixabepilone - no Prior Chemo | Proportion of Patients With Measurable Disease Response (Best Overall Response) | 0.23 proportion of participants |
| Ixabepilone - Prior Taxane | Proportion of Patients With Measurable Disease Response (Best Overall Response) | 0.08 proportion of participants |
| Ixabepilone - Two Prior Chemo | Proportion of Patients With Measurable Disease Response (Best Overall Response) | 0 proportion of participants |