Randomized Phase II Trial of Sipuleucel T Immunotherapy Preceded by Sensitizing Radiation Therapy and Sipuleucel-T Alone in Patients With Castrate Resistant Metastatic Prostate Cancer
Randomized Phase II Trial of Sipuleucel T Immunotherapy Preceded by Sensitizing Radiation Therapy and Sipuleucel-T Alone in Patients With Castrate Resistant Metastatic Prostate Cancer
This randomized phase II trial studies how well giving sipuleucel-T with or without radiation therapy works in treating patients with hormone-resistant metastatic prostate cancer. Vaccines may help the body build an effective immune response to kill tumor cells. Radiation therapy uses high energy x rays to kill tumor cells. It is not yet known whether giving sipuleucel-T vaccine is more effective with or without radiation therapy in treating 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:
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:
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:
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