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

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT02463799
• Collaborator: Dendreon (Industry), Bayer (Industry)
• Enrollment: 36
• Locations: 5
• Arms: 2
• Actual Duration (Months): 45.6
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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 Design

• Study Type: Interventional
• Actual Enrollment: 36 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
• Actual Study Start Date: Feb 22, 2016
• Actual Primary Completion Date: Dec 12, 2019
• Actual Study Completion Date: Dec 12, 2019

Arms and Interventions

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 Names: Xofigo, BAY88-8223 ; Biological: Sipuleucel-T; 3 infusions of sipuleucel-T alone; Other Names: 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 Names: Provenge

Outcome Measures

Primary Outcome Measures

1. Immune Responses to Treatment With Sipuleucel-T (With or Without Radium-223) Measured by Peripheral PA2024 T-cell Proliferation [6 weeks]

   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] ).

Secondary Outcome Measures

1. Peripheral PA2024 Specific T-cell Proliferation as Measured by Stimulation Index Over Time [Up to 52 weeks]

   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.

2. Time to Radiographic or Clinical Progression [Up to 2 years]

   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.

3. PSA50 Response (at Least a 50% Decline in PSA) [Up to 2 years]

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

4. Peripheral PAP Specific T-cell Proliferation as Measured by Stimulation Index Over Time [Up to 52 weeks]

   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

5. Peripheral PA2024 Specific T-cell Activation [Up to 52 weeks]

   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.

6. Peripheral PAP Specific T-cell Activation [Up to 52 weeks]

   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.

7. PA2024 Specific Antibody (IgM) Response [Up to 52 weeks]

   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.

8. PA2024 Specific Antibody (IgG) Response [Up to 52 weeks]

   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.

9. PAP Specific Antibody (IgG) Response Over Time [Up to 52 weeks]

   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.

10. PAP Specific Antibody (IgM) Response [Up to 52 weeks]

    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.

11. Sipuleucel-T Product Immune Parameters as Assessed by Number of CD54+ Cells [Up to 4 weeks]

    Mean number of CD54 + cells

12. Sipuleucel-T Product Immune Parameters as Assessed by CD54+ Upregulation [Up to 4 weeks]

    Mean CD54+ Upregulation of Sipuleucel-T

13. Sipuleucel-T Product Immune Parameters as Assessed by Total Nucleated Cell Count [Up to 4 weeks]

    Mean number of Total Nucleated Cells

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• 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

1. Serum PSA ≥ 2.0 ng/mL

2. Screening ECOG perf status ≤ 1

3. Asymptomatic or minimally symptomatic disease (no narcotic analgesic; other analgesics use is allowed)

4. Prior abiraterone and enzalutamide are permitted, but not required

5. Concurrent osteoclast-inhibitory therapies (zoledronic acid, denosumab) are permitted if patients have been on a stable dose for at least 1 month

6. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
2	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
3	Tulane Cancer Center	New Orleans	Louisiana	United States	70112
4	Johns Hopkins Hospital	Baltimore	Maryland	United States	21231
5	Duke University	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Dendreon
• Bayer

Investigators

• Principal Investigator: Emmanuel Antonarakis, MD, Johns Hopkins University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 21, 2020

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT02463799
• Other Study ID Numbers: J1522; IRB00056435
• First Posted: Jun 4, 2015
• Last Update Posted: Jul 8, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: prostatic neoplasms; castration-resistant; bone metastasis; radium-223; sipuleucel-T
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	One screen failure and one withdrew consent prior to randomization, two participants withdrew prior to receiving treatment

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Period Title: Overall Study
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone	Total
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Total of all reporting groups
Overall Participants	16	16	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 6.3%	5 31.3%	6 18.8%
>=65 years	15 93.8%	11 68.8%	26 81.3%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	71.6	70.3	71
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	16 100%	16 100%	32 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 6.3%	1 3.1%
Not Hispanic or Latino	16 100%	15 93.8%	31 96.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	2 12.5%	2 6.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 25%	4 25%	8 25%
White	11 68.8%	10 62.5%	21 65.6%
More than one race	1 6.3%	0 0%	1 3.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	16 100%	16 100%	32 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	16	16
Median (Inter-Quartile Range) [fold change]	7.0	22.4

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Data was only collected from 13 out of 16 participants in the Sipuleucel-T and radium 223 combination arm and 10 out of 16 participants in the Sipuleucel-T arm

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	13	10
Baseline	1.7	1.4
Week 6	25.7	49.8
Week 10	27.8	42.0
Week 14	23.0	42.2
Week 26	27.2	25.6
Week 39	20.7	25.3
Week 52	16.5	11.8

3. Secondary Outcome

Title	Time to Radiographic or Clinical Progression
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	16	16
Median (95% Confidence Interval) [WEEKS]	38.7	11.9

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	14	15
Count of Participants [Participants]	0 0%	5 31.3%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Data was only collected from 13 out of 16 participants in the Sipuleucel-T and radium 223 combination arm and 10 out of 16 participants in the Sipuleucel-T arm

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	13	10
Baseline	1.1	1.2
Week 6	1.6	12.5
Week 10	3.1	5.7
Week 14	2.3	6.1
Week 26	3.9	1.5
Week 39	4.1	1.8
Week 52	2.2	1.9

6. Secondary Outcome

Title	Peripheral PA2024 Specific T-cell Activation
Description	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

Outcome Measure Data

Analysis Population Description

Data was only collected from 13 out of 16 participants in the Sipuleucel-T and radium 223 combination arm and 10 out of 16 participants in the Sipuleucel-T arm

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	13	10
Baseline	3.6	6.0
Week 6	66.5	194.3
Week 10	72.9	116.4
Week 14	73.6	137.8
Week 26	87.7	169.9
Week 39	27.3	19.0
Week 52	22.4	26.0

7. Secondary Outcome

Title	Peripheral PAP Specific T-cell Activation
Description	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

Outcome Measure Data

Analysis Population Description

Data was only collected from 13 out of 16 participants in the Sipuleucel-T and radium 223 combination arm and 10 out of 16 participants in the Sipuleucel-T arm

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	13	10
Baseline	0.9	4.8
Week 6	7.8	10.9
Week 10	14.1	19.4
Week 14	12.2	9.0
Week 26	10.4	1.0
Week 39	5.0	1.3
Week 52	3.0	0.0

8. Secondary Outcome

Title	PA2024 Specific Antibody (IgM) Response
Description	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

Outcome Measure Data

Analysis Population Description

Data was only collected from 14 out of 16 participants in the Sipuleucel-T and radium 223 combination arm and 14 out of 16 participants in the Sipuleucel-T arm

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	14	14
Baseline	1567.9	2253.6
Week 6	108941.7	164114.3
Week 10	165434.6	214690.9
Week 14	101422.7	185600.0
Week 26	56586.4	28800.0
Week 39	37338.9	204800.0
Week 52	28400.0

9. Secondary Outcome

Title	PA2024 Specific Antibody (IgG) Response
Description	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

Outcome Measure Data

Analysis Population Description

Data was only collected from 14 out of 16 participants in the Sipuleucel-T and radium 223 combination arm and 14 out of 16 participants in the Sipuleucel-T arm

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	14	14
Baseline	382.1	771.4
Week 6	1476.9	7878.6
Week 10	3442.9	23272.7
Week 14	4191.7	15733.3
Week 26	3568.2	7200.0
Week 39	2738.9	25600.0
Week 52	3812.5

10. Secondary Outcome

Title	PAP Specific Antibody (IgG) Response Over Time
Description	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

Outcome Measure Data

Analysis Population Description

Data was only collected from 14 out of 16 participants in the Sipuleucel-T and radium 223 combination arm and 14 out of 16 participants in the Sipuleucel-T arm

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	14	14
Baseline	796.4	1475.0
Week 6	3765.4	10546.4
Week 10	15125.0	44563.6
Week 14	6554.2	6450.0
Week 26	5354.5	51400.0
Week 39	3916.7	204800.0
Week 52	5100

11. Secondary Outcome

Title	PAP Specific Antibody (IgM) Response
Description	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

Outcome Measure Data

Analysis Population Description

Data was only collected from 14 out of 16 participants in the Sipuleucel-T and radium 223 combination arm and 14 out of 16 participants in the Sipuleucel-T arm

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	14	14
Baseline	4714.3	6253.8
Week 6	99209.1	112114.3
Week 10	183184.6	210909.1
Week 14	73250.0	238400.0
Week 26	72363.6	205600.0
Week 39	36425.0	409600.0
Week 52	33200.0

12. Secondary Outcome

Title	Sipuleucel-T Product Immune Parameters as Assessed by Number of CD54+ Cells
Description	Mean number of CD54 + cells
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

Data was only collected from 14 out of 16 participants in the Sipuleucel-T and radium 223 combination arm and 14 out of 16 participants in the Sipuleucel-T arm

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	14	14
Mean (Inter-Quartile Range) [cells x 10 ^ 6]	2730.3	2059.1

13. Secondary Outcome

Title	Sipuleucel-T Product Immune Parameters as Assessed by CD54+ Upregulation
Description	Mean CD54+ Upregulation of Sipuleucel-T
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

Data was only collected from 14 out of 16 participants in the Sipuleucel-T and radium 223 combination arm and 14 out of 16 participants in the Sipuleucel-T arm

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	14	14
Mean (Inter-Quartile Range) [cells x 10^6]	29.8	31.3

14. Secondary Outcome

Title	Sipuleucel-T Product Immune Parameters as Assessed by Total Nucleated Cell Count
Description	Mean number of Total Nucleated Cells
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

Data was only collected from 14 out of 16 participants in the Sipuleucel-T and radium 223 combination arm and 14 out of 16 participants in the Sipuleucel-T arm

Arm/Group Title	Sipuleucel-T and Radium 223 Combination	Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone	Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
Measure Participants	14	14
Mean (Inter-Quartile Range) [cells 10^6]	11580.5	12740.5

Adverse Events

Time Frame	1 year
Arm/Group Title	Sipuleucel-T and Radium 223 Combination		Sipuleucel-T Alone
Arm/Group Description	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 Radium-223: 6 infusions of radium-223 with 3 infusions of sipuleucel-T starting after second dose of radium-223 Sipuleucel-T: 3 infusions of sipuleucel-T alone		Sipuleucel-T will be administered intravenously per standard of care every 2 weeks at weeks 6, 8, and 10 Sipuleucel-T: 3 infusions of sipuleucel-T alone
All Cause Mortality
	Sipuleucel-T and Radium 223 Combination		Sipuleucel-T Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Serious Adverse Events
	Sipuleucel-T and Radium 223 Combination		Sipuleucel-T Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/16 (12.5%)		1/16 (6.3%)
Blood and lymphatic system disorders
Anemia	1/16 (6.3%)	1	0/16 (0%)	0
Renal and urinary disorders
Urinary Retention	0/16 (0%)	0	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/16 (6.3%)	1	0/16 (0%)	0
Other (Not Including Serious) Adverse Events
	Sipuleucel-T and Radium 223 Combination		Sipuleucel-T Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/16 (75%)		12/16 (75%)
Blood and lymphatic system disorders
Anemia	6/16 (37.5%)	6	6/16 (37.5%)	6
Gastrointestinal disorders
Nausea	6/16 (37.5%)	6	4/16 (25%)	4
Diarrhea	8/16 (50%)	8	0/16 (0%)	0
Constipation	2/16 (12.5%)	2	5/16 (31.3%)	5
Vomiting	2/16 (12.5%)	2	2/16 (12.5%)	2
Abdominal Pain	2/16 (12.5%)	2	2/16 (12.5%)	2
General disorders
Pain	12/16 (75%)	12	12/16 (75%)	12
Chills	2/16 (12.5%)	2	6/16 (37.5%)	6
Fatigue	5/16 (31.3%)	5	3/16 (18.8%)	3
Flu Like Symptoms	4/16 (25%)	4	3/16 (18.8%)	3
Fever	2/16 (12.5%)	2	1/16 (6.3%)	1
Edema Limbs	1/16 (6.3%)	1	2/16 (12.5%)	2
Infections and infestations
Catheter Related Infection	0/16 (0%)	0	2/16 (12.5%)	2
Injury, poisoning and procedural complications
Fall	1/16 (6.3%)	1	2/16 (12.5%)	2
Investigations
White Blood Cell Decreased	2/16 (12.5%)	2	0/16 (0%)	0
Platelet Count Decreased	1/16 (6.3%)	1	0/16 (0%)	0
Nervous system disorders
Dizziness	1/16 (6.3%)	1	3/16 (18.8%)	3
Headache	3/16 (18.8%)	3	0/16 (0%)	0
Psychiatric disorders
Insomnia	2/16 (12.5%)	2	1/16 (6.3%)	1
Renal and urinary disorders
Urinary Retention	0/16 (0%)	0	2/16 (12.5%)	2
Vascular disorders
Hypertension	3/16 (18.8%)	3	0/16 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.