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NCT03093428

Study Evaluating the Addition of Pembrolizumab to Radium-223 in mCRPC

Completed Phase 2 Results posted Last updated 28 March 2025
What this trial tests

Phase 2 trial testing Radium-223 in Prostate Cancer in 45 participants. Completed in 28 February 2025.

Timeline
9 June 2017
Primary endpoint
9 April 2020
28 February 2025

Quick facts

Lead sponsorDana-Farber Cancer Institute
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment45
Start date9 June 2017
Primary completion9 April 2020
Estimated completion28 February 2025
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Dana-Farber Cancer Institute

Who can join

18 and older, male only, with Prostate Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Increased Immune Cell Infiltration Across Arms Primary · 2 months

Differences in immune infiltrating cells (CD8+ T-cells and CD4+ T-cells) in bone biopsy specimens were compared from baseline to 8 weeks on study therapy between the treatment arms.

CD4+ T-cell infiltration levels
GroupValue95% CI
Pembrolizumab Plus Radium-2237
Radium-2232
Pembrolizumab Plus Radium-22314
Radium-2233
CD8+ T-cell infiltration levels
GroupValue95% CI
Pembrolizumab Plus Radium-2233
Radium-2231
Pembrolizumab Plus Radium-22318
Radium-2234
Number of Participants With Grade 3 or Higher Treatment Related Adverse Events Secondary · Toxicity was assessed every cycle and up to 22.4 months.

Adverse events were assessed using NCI CTCAE (version 4.0). Treatment related adverse events were those that were deemed as "Definitely", "Probably" and "Possibly" related to the study treatment.

GroupValue95% CI
Pembrolizumab Plus Radium-22313
Radium-2235
Median Progression-Free Survival Secondary · Imaging was performed every 12 weeks and up to 25 months.

Progression-free survival (PFS) is defined as the time from the first dose of study drug to the earlier of the first documentation of definitive disease progression by RECIST v 1.1 for soft tissue disease and PCWG2 guidelines for bone disease or death due to any cause, or censored at last imaging date. Per RECIST, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. For the bone per PCWG2 criteria, appearance of at least 2 new lesions within 12 weeks and confirmed by a

GroupValue95% CI
Pembrolizumab Plus Radium-2236.12.7 – 10.8
Radium-2235.72.6 – NA
Median Overall Survival Secondary · Participants were followed up for ~36 months.

Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive. Median OS is estimated using Kaplan-Meier method.

GroupValue95% CI
Pembrolizumab Plus Radium-22316.912.7 – NA
Radium-22316.09.0 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab Plus Radium-223
Serious: 9/31 (29%)
Deaths: 15/31
Radium-223
Serious: 3/14 (21%)
Deaths: 7/14

Serious adverse events (20 terms)

ReactionSystemPembrolizumab Plus Radium-…Radium-223
Adrenal insufficiencyEndocrine disorders
Back painMusculoskeletal and connective tissue disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Urinary tract infectionInfections and infestations
Abducens nerve disorderNervous system disorders
Acute coronary syndromeCardiac disorders
AnemiaBlood and lymphatic system disorders
Aspartate aminotransferase increasedInvestigations
DehydrationMetabolism and nutrition disorders
DiarrheaGastrointestinal disorders
FeverGeneral disorders
Lung infectionInfections and infestations
Oculomotor nerve disorderNervous system disorders
PainGeneral disorders
Platelet count decreasedInvestigations
Renal calculiRenal and urinary disorders
SepsisInfections and infestations
StrokeNervous system disorders
Urinary tract obstructionRenal and urinary disorders
White blood cell decreasedInvestigations
Other adverse events (130 terms — click to expand)

ReactionSystemPembrolizumab Plus Radium-…Radium-223
FatigueGeneral disorders
Back painMusculoskeletal and connective tissue disorders
AnemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Hot flashesVascular disorders
PainGeneral disorders
ConstipationGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Aspartate aminotransferase increasedInvestigations
DiarrheaGastrointestinal disorders
HypothyroidismEndocrine disorders
Alkaline phosphatase increasedInvestigations
AnorexiaMetabolism and nutrition disorders
AnxietyPsychiatric disorders
HypertensionVascular disorders
Platelet count decreasedInvestigations
Urinary frequencyRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
Bone painMusculoskeletal and connective tissue disorders
HyperglycemiaMetabolism and nutrition disorders
Neutrophil count decreasedInvestigations
Peripheral sensory neuropathyNervous system disorders
Urinary incontinenceRenal and urinary disorders
Alanine aminotransferase increasedInvestigations
Allergic rhinitisRespiratory, thoracic and mediastinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Edema limbsGeneral disorders
HeadacheNervous system disorders
HyperthyroidismEndocrine disorders
HyponatremiaMetabolism and nutrition disorders
InsomniaPsychiatric disorders
Rash acneiformSkin and subcutaneous tissue disorders
Skin infectionInfections and infestations
Thromboembolic eventVascular disorders
ArthritisMusculoskeletal and connective tissue disorders
Blood bilirubin increasedInvestigations
DizzinessNervous system disorders

Most-reported serious reactions: Adrenal insufficiency, Back pain, Pneumonitis, Urinary tract infection, Abducens nerve disorder, Acute coronary syndrome, Anemia, Aspartate aminotransferase increased.

Data from ClinicalTrials.gov NCT03093428 adverse events section.

Sponsor's own description

This research study is studying the safety and tolerability of an investigational combination of drugs, radium-223 plus pembrolizumab as a possible treatment for castration-resistant prostate cancer. The interventions involved in this study are: * Radium-223 * Pembrolizumab

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Radiopharmaceutical therapy in cancer: clinical advances and challenges.
    Sgouros G, Bodei L, McDevitt MR, Nedrow JR. · · 2020 · cited 551× · PMID 32728208 · DOI 10.1038/s41573-020-0073-9
  2. Recent Advances in Prostate Cancer Treatment and Drug Discovery.
    Nevedomskaya E, Baumgart SJ, Haendler B. · · 2018 · cited 176× · PMID 29734647 · DOI 10.3390/ijms19051359
  3. How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer.
    Stultz J, Fong L. · · 2021 · cited 173× · PMID 33820953 · DOI 10.1038/s41391-021-00340-5
  4. Overview of the Most Promising Radionuclides for Targeted Alpha Therapy: The "Hopeful Eight".
    Eychenne R, Chérel M, Haddad F, Guérard F, et al · · 2021 · cited 124× · PMID 34207408 · DOI 10.3390/pharmaceutics13060906
  5. Novel therapies are changing treatment paradigms in metastatic prostate cancer.
    Powers E, Karachaliou GS, Kao C, Harrison MR, et al · · 2020 · cited 89× · PMID 33115529 · DOI 10.1186/s13045-020-00978-z
  6. Past, Current, and Future of Immunotherapies for Prostate Cancer.
    Boettcher AN, Usman A, Morgans A, VanderWeele DJ, et al · · 2019 · cited 89× · PMID 31572678 · DOI 10.3389/fonc.2019.00884
  7. Radium-223 mechanism of action: implications for use in treatment combinations.
    Morris MJ, Corey E, Guise TA, Gulley JL, et al · · 2019 · cited 87× · PMID 31712765 · DOI 10.1038/s41585-019-0251-x
  8. Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials.
    Gdowski AS, Ranjan A, Vishwanatha JK. · · 2017 · cited 83× · PMID 28800754 · DOI 10.1186/s13046-017-0578-1

Verify or expand the search:

Other trials of Radium-223

Trials testing the same drug.

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Trials by the same sponsor.

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