AzTrials
AzTrials

Prostate CancerPhase 2NCT02463799

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

A Phase 2 study testing Radium-223 and Sipuleucel-T in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Radium-223 and Sipuleucel-T
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
5 sitesUnited States
Study dates
22 Feb 2016to 12 Dec 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent provided prior to initiation of study procedures
  • Age ≥ 18 years
  • 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
  • Bone metastases as manifested by one or more lesions on a bone scan performed within 2 months of screening
  • 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.
Show all 20Show fewer
  • 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
  • Serum PSA ≥ 2.0 ng/mL
  • Screening ECOG perf status ≤ 1
  • Asymptomatic or minimally symptomatic disease (no narcotic analgesic; other analgesics use is allowed)
  • Prior abiraterone and enzalutamide are permitted, but not required
  • Concurrent osteoclast-inhibitory therapies (zoledronic acid, denosumab) are permitted if patients have been on a stable dose for at least 1 month
  • 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

Who cannot join

  • The presence of known lung or liver metastases greater than 1.0 cm in the long axis diameter
  • The presence of lymphadenopathy greater than 3 cm in the short-axis diameter
  • The presence of known brain metastases
  • 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
  • Previous treatment with chemotherapy for mCRPC (adjuvant chemotherapy is permitted), or chemotherapy for any reason within 2 years prior to registration
  • Intention to receive chemotherapy within 6 months after enrollment in protocol therapy
Show all 15Show fewer
  • History of radiation therapy, either via external beam or brachytherapy within 28 days prior to registration
  • Systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bony metastases within previous 24 weeks
  • Prior history of other cancers (except non-melanoma skin cancers or low-grade low-stage urothelial cancers)
  • 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
  • Use of opioid analgesics for cancer-related pain
  • Use of experimental drug within 4 weeks of treatment
  • Uncontrolled medical conditions including diabetes, heart failure, COPD, ulcerative colitis, or Crohn's disease
  • Uncontrolled fecal incontinence
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21231

  • Duke University

    Durham, North Carolina, 27710

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Tulane Cancer Center

    New Orleans, Louisiana, 70112

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
Prostate Cancer
Being tested
Radium-223, Sipuleucel-T
Keywords
prostatic neoplasms, castration-resistant, bone metastasis, radium-223, sipuleucel-T
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Radium-223Drug

    Also called Xofigo, BAY88-8223

    6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223

  • Sipuleucel-TBiological

    Also called Provenge

    3 infusions of sipuleucel-T alone

Study groups in NCT02463799
Study groupRoleWhat they receive
sipuleucel-T and radium 223 combinationExperimentalRadium-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
Receives: Drug: Radium-223; Biological: Sipuleucel-T
sipuleucel-T aloneActive comparatorSipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10
Receives: Biological: Sipuleucel-T

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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] ).

    Measured: 6 weeks

Secondary outcomes (13)

  1. 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.

    Measured: Up to 52 weeks

  2. 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.

    Measured: Up to 2 years

  3. 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

    Measured: Up to 2 years

  4. 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

    Measured: Up to 52 weeks

  5. 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.

    Measured: Up to 52 weeks

  6. 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.

    Measured: Up to 52 weeks

  7. 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.

    Measured: Up to 52 weeks

  8. 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.

    Measured: Up to 52 weeks

  9. 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.

    Measured: Up to 52 weeks

  10. 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.

    Measured: Up to 52 weeks

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

    Mean number of CD54 + cells

    Measured: Up to 4 weeks

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

    Mean CD54+ Upregulation of Sipuleucel-T

    Measured: Up to 4 weeks

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

    Mean number of Total Nucleated Cells

    Measured: Up to 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2015 (estimated)
  2. Study start22 Feb 2016
  3. Primary completion12 Dec 2019
  4. Study completion12 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02463799
Sponsor's protocol ID
J1522
Other IDs
IRB00056435
Status last verified
Jun 2021
First submitted
21 May 2015
Last updated
8 Jul 2021
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Marshall CH, Fu W, Wang H, Park JC, DeWeese TL, Tran PT, Song DY, King S, Afful M, Hurrelbrink J, Manogue C, Cotogno P, Moldawer NP, Barata PC, Drake CG, Posadas EM, Armstrong AJ, Sartor O, Antonarakis ES. Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer. Clin Cancer Res. 2021 Mar 15;27(6):1623-1630. doi: 10.1158/1078-0432.CCR-20-4476. Epub 2021 Jan 15.

    PubMed 33451978

  • Gongora ABL, Marshall CH, Velho PI, Lopes CDH, Marin JF, Camargo AA, Bastos DA, Antonarakis ES. Extreme Responses to a Combination of DNA-Damaging Therapy and Immunotherapy in CDK12-Altered Metastatic Castration-Resistant Prostate Cancer: A Potential Therapeutic Vulnerability. Clin Genitourin Cancer. 2022 Apr;20(2):183-188. doi: 10.1016/j.clgc.2021.11.015. Epub 2021 Dec 24. No abstract available.

    PubMed 35027313

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Radium-223 and Sipuleucel-T in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Immune Responses to Treatment With Sipuleucel-T (With or Without Radium-223) Measured by Peripheral PA2024 T-cell Proliferation (time frame: 6 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02463799, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in