GM-CSF for Maintenance of Prostate Cancer for Patients Responding to Taxotere

Study Overview
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Brief Summary
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This trial is designed to investigate the efficacy and safety of GM-CSF used as a maintenance program in patients with androgen-independent prostate cancer (AIPC) who have achieved a maximal response on a taxotere or other chemotherapy schedule.

Detailed Description
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Patients will be treated on this single arm, open label trial until primary end point is met, patient's withdrawal, or investigator's discretion. After achieving a maximal response on taxotere or other chemo schedule they were eligible to enroll in this trial and begin treatment with maintenance GMCSF for 2 weeks followed by 2 weeks of rest. Once progression was documented the patients were taken off study.

Official Title
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A Phase II Pilot Study Investigating the Efficacy and Activity of Single Agent GM-CSF (Leukine) Maintenance Approach in Androgen-independent Prostate Cancer (AIPC) Patients Responding to Taxotere Chemotherapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: GM CSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men >18 years of age. No upper age limit Written informed consent approved by institutional review board should be explained to and signed by patient Documentation of histologically confirmed adenocarcinoma of the prostate. Gleason score of any sum is allowed on this study. Metastatic disease as evidenced by visceral involvement, bone disease, or PSA elevation. Patients should meet the criteria of androgen independent prostate cancer (AIPC). Patients would fulfill these criteria if they continue to progress despite complete androgen blockade (surgical or medical castration with anti-androgen) and despite an anti-androgen withdrawal trial. Failing anti-androgen withdrawal is defined as no decline by 25% or more 3-weeks after stopping anti-androgens. Progression on hormonal therapy is defined as ANY of the following: PSA: 2 consecutive rising PSA values, at least 14-days apart, each being > 5 ng/ml For patients with visceral measurable disease, progression is defined as an increase by 50% or more in the size of measurable areas, or any development of new lesions. For patients with bone-only disease, progression is defined as the appearance of 2 or more new areas of abnormal uptake on a bone scan, when compared to prior imaging studies. Changes in the uptake of already existing lesions will NOT be used to define progressive disease. For patients with bone AND visceral disease, fulfilling any of the criteria in 5.2 or 5.3 is sufficient to define progression. Castration levels of testosterone (< 50 ng/dl) achieved via medical or surgical castration. Patients should continue on LHRH agonists throughout if this is the method used to achieve castration. Life expectancy of at least 6 months Adequate hematologic, renal, and liver function as evidenced by the following: WBC > 2000, ANC > 1000, Platelet count > 100,000, HgB > 9.0 g/dl, Creatinine < 2, Total bilirubin < 2x upper limit of normal, AST and ALT < 3 x upper limit of normal ECOG performance status of 0 or 1. The use of intravenous polyphosphates for bone metastases is allowed. upon completion of the taxotere portion of study, patient can be enrolled & receive GM-CSF if ANY of the following criteria is met: Patients received total of 8 cycles of taxotere & have no signs of disease progression Patients achieved their maximal response despite receiving < than 8 cycles of taxotere. Maximum response is defined as a drop in measures of PSA by 10% or less on 2 consecutive measurements. Patients who have completed their chemotherapy < than 12 weeks prior to opening this trial & still have stable disease without progression (by PSA and radiographically) will be eligible to receive maintenance GM-CSF Exclusion Criteria: presence of brain metastases Known HIV+ status ECOG performance status of 2 or higher Use of investigational agents within 4 weeks of starting Patients with prior exposure to more than one chemotherapy program Patients who have received one chemotherapy schedule can be enrolled on study and receive GM-CSF (the maintenance arm) if their last chemotherapy was taxotere, given within the past 12 weeks, and they have demonstrated NO evidence of progression radiographically and biochemically. Prior exposure to steroids is NOT an exclusion criteria. Patients with other active malignancies (excluding non-melanoma skin cancers)are excluded. Prior malignancies are not exclusion criteria as long as last treatment for such malignancies was over 5 years prior to enrollment. Treatment with investigational products are NOT an exclusion criteria, if therapy was last received over 4 weeks prior to enrollment. Any medical intervention or other condition which, in the opinion of the principle investigator, could compromise adherence with study requirements.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GM-CSF<br>Once patients have finished receiving the chemotherapy and no signs of disease progression they may receive GM-CSF as outlined in the protocol | Drug: GM CSF<br>* 250 ug/m2 daily for 2 weeks followed by 2 weeks of rest<br>* Other names: Leukine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression (TTP) | The primary end point of this study is to evaluate time to disease progression (TTP). TTP is defined as the time from starting taxotere until there is evidence of progressive disease (PD) as defined below (radiographically and/or biochemically). PD was defined as more than 20% in the sum of longest diameter of measurable lesions compared to baseline, and/or evidence of new lesions on imaging studies. Median TTP from GM-CSF administration and Median TTP from start of chemotherapy is being reported | up to 21 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (PSA) | Biochemical PR (Partial Response) was defined as a PSA that decreases by 50% and maintains by at least 3 weeks by confirmatory measurement. Biochemical SD (stable disease) was defined as a PSA that was increased by less than 25% or decreased by less than 50% Biochemical PD (progressive disease) was defined as an increase of at least 25% confirmed 3 weeks after. | up to 21 months | 
| Response Rate (Radiographic) | PR was defined as more than 30% decrease in the sum of the longest diameter of measurable lesions compared to baseline. SD was defined when lesions did not meet criteria for PR or PD. PD was defined as more than 20% increase in the sum of the longest diameter of measurable lesions compared to baseline, and/or evidence of new lesions at imaging studies. The appearance of 2 or more new boney lesions on bone scan development of cord compression, and pathologic fractures constituted PD. | up to 21 months | 
| Median Overall Survival (OS) |  | up to 44 months | 
| Median Number of GM-CSF Cycles |  | up to 12 months |