Study of Sipuleucel-T W/ or W/O Radium-223 in Men With Asymptomatic or Minimally Symptomatic Bone-MCRPC
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Radium-223; Sipuleucel-T
Intervention description: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223; 3 infusions of sipuleucel-T alone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: prostatic neoplasms; castration-resistant; bone metastasis; radium-223; sipuleucel-T

Summary:

      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.
    

Eligibility criteria:

        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