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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02463799
Recruitment Status : Recruiting
First Posted : June 4, 2015
Last Update Posted : June 26, 2018
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief 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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Radium-223 Biological: Sipuleucel-T Phase 2

Detailed Description:

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  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : December 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: sipuleucel-T and radium 223 combination

Radium-223 will be administered by intravenous injection over 1 minute at 50kbq (1.35 microcurie) per kg body weight per standard of care every 4 weeks at weeks 0, 4, 8, 12, 16, and 20

Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10

Drug: Radium-223
6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223
Other Name: Xofigo, BAY88-8223

Biological: Sipuleucel-T
3 infusions of sipuleucel-T alone
Other Name: Provenge

Active Comparator: sipuleucel-T alone
Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10
Biological: Sipuleucel-T
3 infusions of sipuleucel-T alone
Other Name: Provenge

Primary Outcome Measures :
  1. Immune responses to treatment with sipuleucel-T (with or without Radium-223) measured by peripheral PA2024 T-cell proliferation [ Time Frame: 10 weeks ]

Secondary Outcome Measures :
  1. To evaluate peripheral antigen-specific T-cell proliferation over time [ Time Frame: Up to 58 weeks ]
  2. To evaluate peripheral antigen-specific T-cell activation to sipuleucel-T over time [ Time Frame: Up to 58 weeks ]
  3. To evaluate antigen specific antibody response to sipuleucel-T over time [ Time Frame: Up to 58 weeks ]
  4. To evaluate sipuleucel-T induced antigen spread (epitope spread) phenomena [ Time Frame: Up to 18 weeks ]
  5. To evaluate the sipuleucel-T product immune parameters [ Time Frame: Up to 58 weeks ]
  6. To investigate safety of combined use of radium-223 and sipuleucel-T (composite measure of both arms) [ Time Frame: Up to 2 years ]
    Incidence and severity of adverse events and laboratory abnormalities, graded according to CTCAE v4.0

  7. To evaluate time to prostate-specific antigen (PSA) progression [ Time Frame: Up to 2 years ]
  8. To evaluate time to alkaline phosphatase (ALP) progression [ Time Frame: Up to 2 years ]
  9. To evaluate time to pain progression and first cancer-related opioid use [ Time Frame: Up to 2 years ]
  10. To evaluate time to radiographic or clinical progression [ Time Frame: Up to 2 years ]
  11. To evaluate time to first skeletal related event (SRE) [ Time Frame: Up to 2 years ]
  12. To evaluate time to first chemotherapy use [ Time Frame: Up to 2 years ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02463799

Contact: Emmanuel Antonarakis, MD 443-287-0553

United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Edwin Posadas, MD    310-423-7600   
United States, District of Columbia
Sibley Memorial Hospital Recruiting
Washington, District of Columbia, United States, 20016
Contact: Channing Paller, MD    202-660-6500   
Contact: Ashley Bruns, RN    202-537-4000   
Sub-Investigator: Channing Paller, MD         
United States, Louisiana
Tulane Cancer Center Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Oliver Sartor, MD    504-988-7869   
Principal Investigator: Oliver Sartor, MD         
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21231
Contact: Emmanuel Antonarakis, MD    410-287-0553   
Contact: Rana Sullivan, RN    410-614-6337   
Principal Investigator: Emmanuel Antonarakis, MD         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Andrew Armstrong, MD    919-668-4667   
Principal Investigator: Andrew Armstrong, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Principal Investigator: Emmanuel Antonarakis, MD Johns Hopkins University

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT02463799     History of Changes
Other Study ID Numbers: J1522
IRB00056435 ( Other Identifier: JHM IRB )
First Posted: June 4, 2015    Key Record Dates
Last Update Posted: June 26, 2018
Last Verified: June 2018

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
prostatic neoplasms
bone metastasis

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases