Sipuleucel-T With or Without Radiation Therapy in Treating Patients With Hormone-Resistant Metastatic Prostate Cancer

PRIMARY OBJECTIVES:

I. To assess the feasibility, based on percent able or willing to receive all three infusions of sipuleucel-T immunotherapy, when combining sipuleucel-T with radiation therapy to a single site of metastasis delivered one week prior to beginning of sipuleucel-T therapy.

SECONDARY OBJECTIVES:

I. To assess the effect of radiation therapy to single metastasis on immune response (antibody and T-cell proliferation to prostate acid phosphate [PAP] and fusion protein PA2024) generated by sipuleucel-T immunotherapy.

II. To assess the effect of external beam radiotherapy to single metastasis on prostate specific antigen (PSA) response to therapy with sipuleucel-T.

III. To assess the effect of external beam radiotherapy to single metastasis on radiographic response rate to therapy with sipuleucel-T.

IV. To assess the time from the onset of therapy with sipuleucel-T +/- radiation to the need for subsequent therapy for prostate cancer.

V. To assess the toxicity associated with sipuleucel-T +/- radiation.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive sipuleucel-T intravenously (IV) over 60 minutes days 22, 36, and 50.

ARM B: Patients undergo external beam radiation therapy in weeks 1-2. Patients also receive sipuleucel-T as in Arm A.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up until week 60.

Inclusion criteria

• Histologically documented adenocarcinoma of the prostate
• Life expectancy of >= 6 months, Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Metastatic disease as evidenced by soft tissue and/or bony metastases on baseline bone scan and/or computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen or pelvis
• Castration resistant prostatic adenocarcinoma; subjects must have current or historical evidence of disease progression despite castrated level of testosterone (< 50 ng/dL) achieved by orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy; disease progression has to be demonstrated by PSA progression OR progression of measurable disease OR progression of non-measurable disease as defined below:

• PSA: Two consecutive rising PSA values, at least 7 days apart
• Measurable disease: >= 20% increase in the sum of the longest diameters of all measurable lesions or the development of any new lesions; the change will be measured against the best response to castration therapy or against the pre-castration measurements if there was no response
• Non-measurable disease:

• Soft tissue disease: The appearance of 1 or more lesions, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response
• Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response; increased uptake of pre-existing lesions on bone scan does not constitute progression
• White blood cell (WBC) >= 2,500 cells/uL
• Absolute neutrophil count (ANC) >= 1,000 cells/uL
• Platelet count >= 75,000 cells/uL
• Hemoglobin (HgB) >= 9.0 g/dL
• Creatinine =< 2.5 mg/dL
• Total bilirubin =< 2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST, serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT, serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
• Prior chemotherapy with 0-2 regimens is allowed
• Prior radiation therapy to prostate or prostate bed is allowed provided it occurred > 3 months before enrollment to the study

Exclusion criteria

• The presence of liver, or known brain metastases, malignant pleural effusions, or malignant ascites
• Moderate or severe symptomatic metastatic disease, defined as a requirement for treatment with opioid analgesics for cancer-related pain within 21 days prior to registration
• Eastern Cooperative Oncology Group (ECOG) performance status > 2
• Treatment with chemotherapy within 3 months of registration
• Treatment with any of the following medications or interventions within 28 days of registration:

• Systematic corticosteroids; use of inhaled, intranasal, and topical steroids is acceptable
• Any other systemic therapy for prostate cancer (except for medical castration)
• History of external beam radiation therapy to metastatic sites within 1 year of enrollment to the study
• Participation in any previous study involving sipuleucel-T
• Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression
• Concurrent other malignancy with the exception of:

• Cutaneous squamous cell and basal carcinomas
• Adequately treated stage 1-2 malignancy
• Adequately treated stage 3-4 malignancy that has been in remission for >= 2 years at the time of registration
• A requirement for systemic immunosuppressive therapy for any reason
• Any infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5 degrees Fahrenheit [F] or 38.1 degrees Celsius [C]) within 1 week prior to registration
• Any medical intervention or other condition which, in the opinion of the principal investigator could compromise adherence with study requirements or otherwise compromise the study's objectives