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

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

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.

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.

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