A Phase 2 Study of Sipuleucel-T With or Without Radium-223 in Men With Asymptomatic or Minimally Symptomatic Bone-Metastatic Castrate-Resistant Prostate Cancer


Condition: Prostate Cancer

Intervention:

  • Drug: Radium-223
  • Biological: Sipuleucel-T

Purpose: 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02463799

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Primary Outcome Measures:

  • Measure: Immune responses to treatment with sipuleucel-T (with or without Radium-223) measured by peripheral PA2024 T-cell proliferation
  • Time Frame: 10 weeks
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: To evaluate peripheral antigen-specific T-cell proliferation over time
  • Time Frame: Up to 58 weeks
  • Safety Issue:
  • Measure: To evaluate peripheral antigen-specific T-cell activation to sipuleucel-T over time
  • Time Frame: Up to 58 weeks
  • Safety Issue:
  • Measure: To evaluate antigen specific antibody response to sipuleucel-T over time
  • Time Frame: Up to 58 weeks
  • Safety Issue:
  • Measure: To evaluate sipuleucel-T induced antigen spread (epitope spread) phenomena
  • Time Frame: Up to 18 weeks
  • Safety Issue:
  • Measure: To evaluate the sipuleucel-T product immune parameters
  • Time Frame: Up to 58 weeks
  • Safety Issue:
  • Measure: To investigate safety of combined use of radium-223 and sipuleucel-T (composite measure of both arms)
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: To evaluate time to prostate-specific antigen (PSA) progression
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: To evaluate time to alkaline phosphatase (ALP) progression
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: To evaluate time to pain progression and first cancer-related opioid use
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: To evaluate time to radiographic or clinical progression
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: To evaluate time to first skeletal related event (SRE)
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: To evaluate time to first chemotherapy use
  • Time Frame: Up to 2 years
  • Safety Issue:

Estimated Enrollment: 34

Study Start Date: December 2015

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

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

Contact:

  • Emmanuel Antonarakis, MD
  • 443-287-0553

Locations:

  • Cedars-Sinai Medical Center
  • Los Angeles California 90048 United States
  • Sibley Memorial Hospital
  • Washington District of Columbia 20016 United States
  • Tulane Cancer Center
  • New Orleans Louisiana 70112 United States
  • Johns Hopkins Hospital
  • Baltimore Maryland 21231 United States
  • Duke University
  • Durham North Carolina 27710 United States

View trial on ClinicalTrials.gov


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