Study of Sipuleucel-T W/ or W/O Radium-223 in Men With Asymptomatic or Minimally Symptomatic Bone-MCRPC

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins36 enrolled

Overview

This clinical trial studies the effect of radium-223 when added to sipuleucel-T for treating castrate-resistant prostate cancer that has spread to the bone. Sipuleucel-T is an autologous cellular immunotherapy designed to stimulate an immune response against prostate cancer. It has been suggested that the immune response may be strengthened by radiation therapy. Therefore this study is testing whether radium-223 added to sipuleucel-T increases the immune response and anti-tumor effect against prostate cancer.

This is a randomized study designed to assess the antigen-specific immune response of sipuleucel-T with or without radium-223. Eligible subjects will be registered and randomly assigned in a 1:1 ratio to receive sipuleucel-T and radium-223 or sipuleucel-T alone. Subjects in both arms (sipuleucel-T and radium) will undergo a standard 1.5 to 2.0 blood volume leukapheresis, followed approximately 3 days later by an IV infusion of sipuleucel-T. This process will occur a total of 3 times at approximately 2-week intervals. Subjects in Arm 1 will receive a total of 6 infusions of radium-223 at IV dose of 50 kBq/kg at 4-week interval. All participants are allowed to receive the best supportive care which includes secondary hormonal manipulation as required. No chemotherapy, external-beam radiation, or other radionuclides are allowed while on active treatment but are permitted after completion of active treatment. Glucocorticoid-containing treatments should be minimized to less than the equivalent dose of prednisone 10mg daily if feasible for the 3 months following sipuleucel-T therapy. All patients continue medical or surgical castration during treatment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Written informed consent provided prior to initiation of study procedures 2. Age ≥ 18 years 3. Histologically documented adenocarcinoma prostate cancer confirmed by a pathology report from prostate biopsy or a radical prostatectomy specimen. If prostatic tumor is of mixed histology, \> 50% of the tumor must be adenocarcinoma 4. Bone metastases as manifested by one or more lesions on a bone scan performed within 2 months of screening 5. Castrate-resistant prostate cancer, in the setting of castrate levels of testosterone (≤ 50 ng/dL), defined as current or historical evidence of disease progression concomitant with surgical castration or androgen deprivation therapy (ADT), as demonstrated by two consecutive rises in PSA OR new lesions on bone scan: * PSA progression will be defined as 2 rising PSA values compared to a reference value, measured at least 7 days apart and the second value is ≥ 2 ng/mL \[1\]. It must be documented within 2 months of screening. * Appearance of one or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the precastration studies if there was no response. Increased uptake of pre-existing lesions on bone scan does not constitute progression. It must be documented within 4 months of screening 6. Serum PSA ≥ 2.0 ng/mL 7. Screening ECOG perf status ≤ 1 8. Asymptomatic or minimally symptomatic disease (no narcotic analgesic; other analgesics use is allowed) 9. Prior abiraterone and enzalutamide are permitted, but not required 10. Concurrent osteoclast-inhibitory therapies (zoledronic acid, denosumab) are permitted if patients have been on a stable dose for at least 1 month 11. Adequate screening hematologic, renal, and liver function as evidenced by laboratory test results within the following ranges ≤ 28 days prior to registration: * Absolute neutrophil count (ANC) ≥ 1.5 x109/L * Platelet count ≥ 100 x109/L * Hemoglobin ≥ 10.0 g/dL * Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN * Creatinine ≤ 1.5 x ULN * Albumin \> 25 g/L Exclusion Criteria: 1. The presence of known lung or liver metastases greater than 1.0 cm in the long axis diameter 2. The presence of lymphadenopathy greater than 3 cm in the short-axis diameter 3. The presence of known brain metastases 4. Spinal cord compression, imminent long bone fracture, or any other condition that, in the opinion of the investigator, is likely to require radiation therapy and/or steroids for pain control during the active phase 5. Previous treatment with chemotherapy for mCRPC (adjuvant chemotherapy is permitted), or chemotherapy for any reason within 2 years prior to registration 6. Intention to receive chemotherapy within 6 months after enrollment in protocol therapy 7. History of radiation therapy, either via external beam or brachytherapy within 28 days prior to registration 8. Systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bony metastases within previous 24 weeks 9. Prior history of other cancers (except non-melanoma skin cancers or low-grade low-stage urothelial cancers) 10. Use of prednisone or equivalent systemic corticosteroid within 2 weeks of treatment. Use of inhaled, intranasal, intra-articular, and topical steroids is allowed. Oral or IV steroids to prevent or treat IV contrast reactions are allowed 11. Use of opioid analgesics for cancer-related pain 12. Use of experimental drug within 4 weeks of treatment 13. Uncontrolled medical conditions including diabetes, heart failure, COPD, ulcerative colitis, or Crohn's disease 14. Uncontrolled fecal incontinence 15. Any medical intervention, any other condition, or any other circumstance which, in the opinion of the investigator, could compromise adherence with study requirements or otherwise compromise the study's objectives

Locations (5)

Cedars-Sinai Medical Center

Los Angeles, California, United States

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Tulane Cancer Center

New Orleans, Louisiana, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Duke University

Durham, North Carolina, United States

Outcomes

Primary Outcomes

Immune Responses to Treatment With Sipuleucel-T (With or Without Radium-223) Measured by Peripheral PA2024 T-cell Proliferation

Peripheral PA2024-specific T-cell proliferation responses using a 3H-thymidine incorporation assay at 6 weeks after the first dose of sipuleucel-T, measured by SI (Stimulation Index \[3H-thymidine incorporation in the presence of antigen divided by 3H-thymidine incorporation with media alone\] ).

Time frame: 6 weeks

Secondary Outcomes

Peripheral PA2024 Specific T-cell Proliferation as Measured by Stimulation Index Over Time

Mean peripheral PA2024 specific T-cell proliferation using a 3H-thymidine incorporation assay reported as SI (Stimulation Index \[3H-thymidine incorporation in the presence of antigen divided by 3H-thymidine incorporation with media alone\] ) at baseline and 6, 10, 14, 26, 39, and 52 weeks after the first infusion of sipuleucel-T.

Time frame: Up to 52 weeks

Time to Radiographic or Clinical Progression

Number of weeks from baseline until radiographic or clinical progression, whichever comes first. Radiographic progression is assessed by RECIST (Response Evaluation Criteria in Solid Tumors) and PCWG2 criteria (Prostate Cancer Working Group 2). Per RECIST, progression is defined as ≥ 20% and ≥ 5 mm from nadir of the sum of the diameters of target lesions. Per PCWG2 criteria, radiographic progression is defined as ≥ 20% sum of the longest diameter of target lesions, or ≥ 2 new lesions on bone scan from baseline. Clinical progression is defined as new spinal cord or nerve root compression, new pathologic fracture or use of opioid analgesics for cancer-related pain.

Time frame: Up to 2 years

PSA50 Response (at Least a 50% Decline in PSA)

Number of participants with PSA50 response defined as at least a 50% decline in Prostate Specific Antigen (PSA) from baseline value

Time frame: Up to 2 years

Peripheral PAP Specific T-cell Proliferation as Measured by Stimulation Index Over Time

Mean peripheral PAP specific T-cell proliferation using a 3H-thymidine incorporation assay reported as SI (Stimulation Index \[3H-thymidine incorporation in the presence of antigen divided by 3H-thymidine incorporation with media alone\] ) at baseline and 6, 10, 14, 26, 39, and 52 weeks after the first infusion of sipuleucel-T

Time frame: Up to 52 weeks

Peripheral PA2024 Specific T-cell Activation

Mean peripheral PA2024 specific T-cell activation to sipuleucel-T using interferon gamma (IFNγ) enzyme-linked immunosorbent spot (ELISPOT), as measured by cells per 300,000 PBMCs at baseline and weeks 6, 10, 14, 26, 39, and 52 weeks after the first infusion of sipuleucel-T.

Time frame: Up to 52 weeks

Peripheral PAP Specific T-cell Activation

Mean peripheral PAP specific T-cell activation to sipuleucel-T using interferon gamma (IFNγ) enzyme-linked immunosorbent spot (ELISPOT) measured as cells per 300,000 PBMCs at baseline and weeks 6, 10, 14, 26, 39, and 52 weeks after the first infusion of sipuleucel-T.

Time frame: Up to 52 weeks

PA2024 Specific Antibody (IgM) Response

Mean titer of PA2024 specific antibody (IgM) response to sipuleucel-T using enzyme-linked immunosorbent assay (ELISA) at baseline and weeks 6, 10, 14, 26, 39, and 52 weeks after the first infusion of sipuleucel-T.

Time frame: Up to 52 weeks

PA2024 Specific Antibody (IgG) Response

Mean titer of PA2024 specific antibody (IgG) response to sipuleucel-T using enzyme-linked immunosorbent assay (ELISA) at baseline and weeks 6, 10, 14, 26, 39, and 52 weeks after the first infusion of sipuleucel-T.

Time frame: Up to 52 weeks

PAP Specific Antibody (IgG) Response Over Time

Mean titer of PAP specific antibody (IgG) response to sipuleucel-T using enzyme-linked immunosorbent assay (ELISA) at baseline and weeks 6, 10, 14, 26, 39, and 52 weeks after the first infusion of sipuleucel-T.

Time frame: Up to 52 weeks

PAP Specific Antibody (IgM) Response

Mean titer of PAP specific antibody (IgM) response to sipuleucel-T using enzyme-linked immunosorbent assay (ELISA) at baseline and weeks 6, 10, 14, 26, 39, and 52 weeks after the first infusion of sipuleucel-T.

Time frame: Up to 52 weeks

Sipuleucel-T Product Immune Parameters as Assessed by Number of CD54+ Cells

Mean number of CD54 + cells

Time frame: Up to 4 weeks

Sipuleucel-T Product Immune Parameters as Assessed by CD54+ Upregulation

Mean CD54+ Upregulation of Sipuleucel-T

Time frame: Up to 4 weeks

Sipuleucel-T Product Immune Parameters as Assessed by Total Nucleated Cell Count

Mean number of Total Nucleated Cells

Time frame: Up to 4 weeks

Study of Sipuleucel-T W/ or W/O Radium-223 in Men With Asymptomatic or Minimally Symptomatic Bone-MCRPC

Overview

Conditions

Interventions

Eligibility

Locations (5)

Outcomes

Primary Outcomes

Secondary Outcomes