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

Phase 2

Completed

Conditions: Soft Tissue Metastases
Stage IV Prostate Cancer
Recurrent Prostate Cancer
Adenocarcinoma of the Prostate
Bone Metastases
Hormone-resistant Prostate Cancer

Registration Number: NCT01807065

Lead Sponsor: City of Hope Medical Center

Brief Summary: 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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 51

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	Until progression or death, Up to 2 years.	Estimated using the product-limit method of Kaplan and Meier. Progression is defined as one or more of the following: 20% increase in the sum of the longest diameters of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesions; PSA increase of 25% from baseline or nadir and by 2ng/uL or greater at 12 weeks; death due to disease without prior documentation of progression and without symptomatic deterioration.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Grade 2 or Above Adverse Events	Up to 60 weeks	Number of participants with specified adverse event that is grade 2 or above and related to treatment. Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

Trial Locations

Locations (3): City of Hope Medical Center
🇺🇸
Duarte, California, United States
South Pasadena Cancer Center
🇺🇸
Pasadena, California, United States
Huntsman Cancer Institute, Univ. of Utah
🇺🇸
Salt Lake City, Utah, United States
City of Hope Medical Center
🇺🇸Duarte, California, United States