Xofigo (radium Ra-223 dichloride)

P=N/A, N=60, Not yet recruiting, The Netherlands Cancer Institute

P1, N=8, Terminated, Bayer | Phase classification: P1/2 --> P1

BMM are significantly associated with scintigraphic extent of skeletal disease and OS in patients with mCRPC. Particularly, the bone resorption marker CTX-MMP is a promising surrogate marker for prediction of outcome in patients receiving Radium-223 therapy and could potentially improve selection of patients for therapy and assessment of response.

P=N/A, N=80, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Initiation date: Sep 2024 --> Dec 2024

P2, N=70, Active, not recruiting, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori | Recruiting --> Active, not recruiting

External beam radiotherapy is used for radical treatment of organ-confined prostate cancer and to treat lesions in metastatic disease whereas molecular radiotherapy with labelled prostate-specific membrane antigen ligands and radium-223 (223Ra) is indicated for metastatic prostate cancer and has demonstrated substantial improvements in symptom control and overall survival compared with standard-of-care treatment...In vitro data demonstrate that single-dose radiotherapy regimes induce a greater immune-suppressive profile than fractionated regimes; less is known about the immune response induced by molecular radiotherapy agents, but evidence suggests that these agents might induce an immune-suppressive systemic immune response, indicated by increased expression of inhibitory checkpoint molecules such as programmed cell death 1 ligand 1 and 2, and that these changes could be associated with clinical response. Different radiotherapy modalities can induce distinct immune profiles, which can either activate or suppress immune-mediated tumour killing and the current preclinical models used for prostate cancer research are not yet optimal for studying the complexity of the radiotherapy-induced immune response.

P=N/A, N=48, Recruiting, University of Washington | Trial primary completion date: Aug 2024 --> Aug 2025

P1/2; Suspended --> Active, not recruiting

P4, N=696, Active, not recruiting, Bayer | Trial completion date: May 2025 --> May 2026

Our study shows that Ra-223 affects bone structures that are not involved in bone metastasis. Strategies that improve bone health may reduce fracture risk in patients receiving Ra-223.

P2, N=45, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jun 2024 --> Sep 2024

P=N/A, N=194, Completed, Bayer | Active, not recruiting --> Completed

A 71-year-old man with bone metastasis of hormone-sensitive prostate cancer was treated with androgen deprivation therapy and apalutamide. Radium-223 and radiation therapy were administered after it become castration resistant...In this case, if the diagnosis of aggressive variant prostate cancer had been made at an earlier time by biopsy specimens, there might have been a possibility to improve the prognosis by the earlier introduction of the platinum-based regimen. The online version contains supplementary material available at 10.1007/s13691-024-00673-7.

P2, N=70, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

P2, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=136 --> 12

P=N/A, N=80, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2029 --> Aug 2029 | Initiation date: May 2024 --> Aug 2024 | Trial primary completion date: May 2028 --> Aug 2028

P1/2, N=36, Recruiting, University of Utah | Trial completion date: Apr 2025 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2025

P4, N=696, Active, not recruiting, Bayer | Recruiting --> Active, not recruiting

P2, N=70, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies.

The median age, Gleason score, and prior chemo/hormonal therapies were similar for EZ+ and EZ-, except for radium-223. Enzalutamide treatment prior to Lu-PSMA does not improve patient outcomes when applied remotely. Larger studies evaluating the combination therapies and the timing of enzalutamide are needed to assess its correlation with Lu-PSMA outcomes.

P1/2, N=90, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P=N/A, N=80, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

P=N/A, N=1474, Active, not recruiting, Bayer | Trial completion date: Feb 2025 --> Oct 2024

29 (58%) with prior >2 ARPI, 29 (58%) with >1 chemo, 14 (28%) with Ra-223, 2 (4%) with 177 Lu-J591... A single-cycle of fractionated-dose 177Lu-PSMA-617 is safe. Despite no pre-selection for PSMA expression, most had PSA decline with favorable PFS and OS compared to historical controls and similar to PSMA-selected targeted radionuclide studies administering multiple cycles in a less dose-intense approach.

P=N/A, N=1, Completed, Pfizer | Trial completion date: Jun 2023 --> Apr 2024 | Trial primary completion date: Jun 2023 --> Apr 2024

P3, N=446, Active, not recruiting, European Organisation for Research and Treatment of Cancer - EORTC | Trial completion date: Dec 2025 --> Dec 2028

Clinical responders possessed lower circulating frequencies of Ki67+ T and myeloid cells at baseline and higher circulating frequencies of TIM-3+ T and myeloid cells by week 9. Although R223+P did not induce T-cell infiltration into the tumor microenvironment, exhaustion of induced peripheral T-cell immune responses may dampen the combination's clinical activity.

P1, N=43, Active, not recruiting, Tufts Medical Center | Recruiting --> Active, not recruiting | N=25 --> 43 | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

As determined by receiver operating characteristic (ROC) curve analysis, tetanus-specific IL-10 spots at baseline had the highest predictive value (p = 0.005) for tumor burden at month 6, with an area under the curve (AUC) of 0.90 (sensitivity 100%, specificity 78%). In conclusion, we observed an additive effect of treatment with 223Ra on immune function and found that IL-10 secretion at baseline predicted tumor burden at month 6 after treatment.

P3, N=806, Completed, Bayer | Active, not recruiting --> Completed

P4, N=255, Completed, Bayer | Active, not recruiting --> Completed

P=N/A, N=1474, Active, not recruiting, Bayer | Trial primary completion date: Nov 2024 --> Aug 2024

Quantitative bone scan assessment with aBSI and CTC analyses are prognostic markers in patients treated with radium-223. AR-V7 expression in CTCs is a particularly promising prognostic biomarker and warrants validation in larger cohorts.

P1/2, N=90, Suspended, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P2, N=20, Completed, University of Utah | Active, not recruiting --> Completed | Trial completion date: Aug 2024 --> Aug 2023

P2, N=54, Not yet recruiting, University of California, San Francisco | Initiation date: Dec 2023 --> Apr 2024

P4, N=24, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting | Trial completion date: Dec 2022 --> Jul 2024 | Trial primary completion date: Dec 2022 --> Sep 2023

P1/2; Recruiting --> Suspended

P=N/A; Active, not recruiting --> Completed

The inflammatory cytokine IL-6 and the angiogenic biomarker PlGF at baseline were promising outcome biomarkers after standard Ra223 treatment. In mouse models, Ra223 increased intratumoral CD8 T cell infiltration and proliferation and could improve OS when combined with anti-PD1 ICI.