Phase II GM-CSF Plus Mitoxantrone in Hormone Refractory Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of the combination of mitoxantrone and granulocyte-macrophage colony stimulating factor (GM-CSF) on progression-free survival (PFS) and overall survival (OS), in patients with hormone-refractory prostate cancer.

Detailed Description
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This trial evaluates if the addition of GM-CSF to standard-of-care therapy after 1st-line docetaxel improves tumor control and survival. Because the 2 drugs have completely different mechanisms of action as well as non-overlapping metabolism, clinically significant drug-drug interactions are not anticipated, and therefore both drugs will be given at standard (approved) doses.

Official Title
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Phase II Study of Granulocyte-Macrophage Colony Stimulating Factor Plus Mitoxantrone for the Treatment of Hormone Refractory Prostate Cancer

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: Mitoxantrone
* Drug: GM-CSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Age ≥ 18 years Histologically-confirmed adenocarcinoma of the prostate Hormone-refractory prostate cancer Failed 1st-line docetaxel-containing regimen No prior immunotherapy including: Vaccines GM-CSF Minimum prostate-specific antigen (PSA) > 5 mg/dL and rising according to the PSA Consensus Criteria Karnofsky Performance Status (KPS) > 60% Eastern Cooperative Oncology Group (ECOG) Performance Status < 3 Life expectancy > 6 months Exclusion Criteria: Concomitant hormonal therapy other than luteinizing hormone-releasing hormone (LHRH) agonist Use of herbal products known to decrease PSA levels Use of supplements or complementary medicines, except for: Conventional multivitamin supplements Selenium Lycopene Soy supplements Vitamin E Initiation of bisphosphonates within one month prior to enrollment or throughout the study Any prior radiopharmaceuticals (strontium, samarium) within 8 weeks prior to enrollment Major surgery or radiation therapy completed < 4 weeks prior to enrollment Any concomitant second malignancy other than non-melanoma skin cancer Any concomitant serious infection Any nonmalignant medical illness Absolute neutrophil count (ANC) < 1,500/µL Platelet count < 100,000 µL Hemoglobin < 8 mg/dL Total bilirubin greater than 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN if no demonstrable liver metastases, or greater than 5.0 x ULN in presence of liver metastases Ejection fraction < 50% as measured by echocardiogram (ECHO) or multigated acquisition (MUGA) scan Noncompliance with study procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

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 Plus Mitoxantrone<br>GM-CSF at 250 micrograms/ m² / day subcutaneously 3 x week for 3 weeks. Participants will also receive mitoxantrone 14 mg/m² on Day 1 of each cycle. Each cycle of therapy consists 21 days. | Drug: Mitoxantrone<br>* Mitoxantrone is an anti-cancer chemotherapy drug that is classified as an antitumor antibiotic.<br>* Other names: Novantrone;Drug: GM-CSF<br>* GM-CSF is a biologic response modifier, classified as a colony stimulating factor.<br>* Other names: Granulocyte-Macrophage Colony Stimulating Factor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Assessed as the time from the 1st dose of study drug to death or disease progression (increase >25% over baseline PSA on 2 consecutive measurements 2 weeks apart, need for palliative therapy, formation/progression of new bone lesions, or decline of >20% KPS) | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With > 50% Decrease in Prostate-specific Antigen Levels (PSA Response) | Defined as the first evidence of a total serum PSA decline of > 50% from baseline, maintained for at least 28 days, and confirmed with 2 consecutive measurements taken 2 weeks apart. | 18 months | 
| Overall Survival (OS) | Assessed as the time from the 1st dose of study drug to death. | 18 months |