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

Phase 2

Terminated

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
GM-CSF Plus Mitoxantrone	Mitoxantrone	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.
GM-CSF Plus Mitoxantrone	GM-CSF	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.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	18 months	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)

Secondary Outcome Measures

Name	Time	Method
Number of Participants With > 50% Decrease in Prostate-specific Antigen Levels (PSA Response)	18 months	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.
Overall Survival (OS)	18 months	Assessed as the time from the 1st dose of study drug to death.