Introduction
Radiopharmaceutical | Trade name | Half-life (days) | Major emission | Linear energy transfer (MeV) | Tissue range | Indication |
---|---|---|---|---|---|---|
Beta emitters | ||||||
Strontium-89 (89SrCl2) | Metastron® | 50.5 | Beta | 0.58 | 0.7 cm | Adjunct to and as an alternative to external beam radiotherapy for the palliation of pain from the bone metastases secondary to prostatic carcinoma at the stage of hormone therapy failure |
Samarium-153-EDTMP (153Sm-EDTMP,153Sm lexidronam) | Quadramet® | 1.9 | Beta | 0.22 | 0.33 cm | Pain relief in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scan |
Alpha-emitter | ||||||
Radium-223 (223RaCl2) | Xofigo® | 11.4 | Alpha | 27.4 | 100 μm | Treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease |
Comparison of Physical Characteristics of Radionuclides: Advantages of Alpha Versus Beta Emitters
Pain Palliation With the Beta Emitters Strontium-89 and Samarium-153
Beta Emitters With Prior or in Combination With Chemotherapy or EBRT
Improving Survival in Metastatic CRPC With Radium-223
Efficacy: OS
Efficacy: SSE
Efficacy: Biochemical Markers
Efficacy: QOL and Effect on Bone Pain
Trial | Trial design | Primary and secondary end points | Trial start date, estimated trial completion datea, and planned enrollment |
---|---|---|---|
NCT02278055 | A phase 2, open-label, nonrandomized trial to assess pain efficacy with radium-223 in symptomatic mCRPC within 12 weeks of treatment | Primary: pain response Secondary: changes in bone ALP and other bone biomarkers | October 2014, October, 2016, 15 |
NCT02023697 | A three-arm, randomized, open-label phase 2 trial of radium-223 dichloride 50 vs. 80 kBq/kg, and vs. 50 kBq/kg in an extended dosing schedule in CRPC patients with bone metastasis | Primary: SSE-free survival Secondary: OS, time to first SSE, rPFS, time to radiologic progression, pain improvement rate, time to pain progression, number of patients with TEAEs or SAEs, change in 24-h analgesic use | March 2014, October 2018, 389 |
NCT02346526 | A single-arm, open-label, phase 2 biomarker trial of radium-223 in mCRPC patients | Primary: change from baseline in bone scan index at 2 months Secondary: mean percentage change in bone lesion area by 18-month survival status, changes in CTC number, circulating biomarkers of tumor microenvironment, changes in CTC number and translational biomarkers | May 2015, July 2021, 22 |
NCT02204943 | An interventional, open-label pharmacodynamic trial of radium-223 in CRPC patients with bone metastases | Primary: change in proportion of patients who overexpress ALP in bone metastases Secondary: change in biomarkers of epithelial plasticity and osteomimicry expressed in the metastases of men with bone metastatic CRPC | October 2014, October 2016, 20 |
NCT02141438, REASSURE | An observational trial in the routine clinical practice setting to evaluate the short- and long-term safety of radium-223 in mCRPC patients and to evaluate the risk of developing second primary cancers | Primary: incidence of developing second primary malignancies, incidence of treatment-emergent SAEs, incidence of drug-related TEAE, incidence of drug-related SAEs, bone marrow suppression Secondary: OS, the worst pain score and pain interference score over time as determined by patient responses on the Brief Pain Inventory (short form) questionnaire | August 2014, September 2023, 1334 |
NCT02034552 | A randomized, open-label, phase 2a trial evaluating quantified bone scan response following treatment with radium-223 alone or in combination with abiraterone acetate or enzalutamide in CRPC patients with bone metastases | Primary: patient bone scan response Secondary: rPFS, SSE-FS, time to first SSE, OS, time to radiologic bone progression by treatment group, number of patients with TEAE, and number of patients with SAE | December 2013, June 2016, 66 |
NCT02463799 | A phase 2, randomized of sipuleucel-T with or without radium-223 in men with asymptomatic or minimally symptomatic bone-metastatic CRPC | Primary: immune response to treatment with sipuleucel-T (with or without radium-223) measured by peripheral PA2024 T-cell proliferation Secondary: peripheral antigen-specific T-cell proliferation over time, peripheral antigen-specific T-cell activation to sipuleucel-T over time, antigen-specific antibody response to sipuleucel-T over time, sipuleucel-T-induced antigen spread (epitope spread) phenomena, the sipuleucel-T product immune parameters, safety of combined use of radium-223 and sipuleucel-T, time to PSA progression, time to ALP progression, time to pain progression and first cancer- related opioid use, time to radiographic or clinical progression, time to first SRE, time to first chemotherapy use | July 2015, December 2018, 34 |
NCT02043678 (ERA223) | A randomized, phase 3, double-blind, placebo-controlled trial of radium-223 dichloride in combination with abiraterone acetate and prednisone/prednisolone in the treatment of asymptomatic or mildly symptomatic chemotherapy-naïve subjects with bone predominant mCRPC | Primary: SSE-free survival Secondary: OS, time to opiate use for cancer pain, time to pain progression, time to cytotoxic chemotherapy, rPFS, number of patients with AEs | March 2014, December 2017, 800 |
NCT02398526, PARABO | An observational, prospective, single-arm cohort trial for pain evaluation in radium-223-treated patients with bone metastases | Primary: pain response Secondary: change of pain over time, change in bone-pain related QOL, pain control rate, pain progression rate, time to first pain progression, time to first opioid use, summary of evaluation of covariates on pain response, relation between bone uptake in known lesions and pain palliation, dosage of radium-223, number of injections of radium-223, course of blood count, number of patients with TEAE, time to next tumor treatment, time to first SSE, OS | March 2015, September 2017, 300 |
NCT01810770 | An interventional, phase 3, single-arm, international, open-label, prospective trial to evaluate safety and efficacy of radium-223 dichloride in an Asian population with CRPC metastatic to the bone | Primary: number of patients with AEs, number of patients with laboratory changes, number of patients with changes in vital signs, number of patients with changes in ECG, OS Secondary: changes in total ALP, number of patients with total ALP normalization, time to total ALP progression, changes in PSA, time to PSA progression, time to first SRE, SRE-free survival, time to first SRE, time to occurrence of first use of radio-isotopes to relieve skeletal symptoms, time to occurrence of first start of any other anticancer treatment, time to occurrence of first deterioration of ECOG performance status, QOL | March 2013, September 2016, 234 |
NCT02331303 | An observational trial to evaluate the extent of potential off-label use of radium-223 (Xofigo®) in Sweden | Primary: proportion of men with mCRPC of radium-223 use, proportion of being women of radium-223 use, proportion of being children of radium-223 use, proportion of bone metastasis but having a diagnosis other than mCRPC, dosage of radium-223, proportion of patients of dose outside label recommendation | April 2015, June 2016, 200 |
NCT02450812 (URANIS) | An observational, prospective, single-arm cohort trial to assess OS, SSE-free survival, and QOL of chemo-naïve mCRPC patients receiving radium-223 under real-life conditions in Germany | Primary: OS Secondary: evaluation of covariates on OS in mCRPC patients, SSE-FS, covariates on SSE-FS, time to next tumor treatments, incidence of TEAE, QOL, activities of daily living, body function | May 2015, November 2019, 500 |
NCT02194842 (mCRPC-PEACEIII) (not yet recruiting patients) | A randomized, multicenter phase 3 trial comparing enzalutamide vs. a combination of radium-223 and enzalutamide in asymptomatic or mildly symptomatic CRPC with metastasis to bone | Primary: rPFS Secondary: OS, prostate cancer-specific survival, first SSE, time and incidence of first skeletal progression-free, time from entry to initiation of next systemic therapy, treatments elected after first disease progression, second progression-free survival in sequential regimen, pain, time to pain progression, occurrence of AEs, time to first use of opioid analgesics, QOL | December 2014, October 2018, 560 |
NCT02396368 (not yet recruiting patients) | A phase 1/1b trial of radium-223 in combination with tasquinimod for CRPC patients with bone metastases Note: Active Biotech and Ipsen have decided to discontinue development of tasquinimod in prostate cancer (press release 4-16-15) | Primary: safety of combining radium-223 with tasquinimod Secondary: bone ALP response, time to radiographic or clinical progression or death, time to first symptomatic SRE, proportion of patients without symptomatic progression at 6 months, median change in bone scan index (BSI) within patients at 12 weeks compared to baseline bone scan, PSA progression, time to death after start of trial treatment, changes in bone markers | March 2015, July 2017, 44 |
NCT02456571 (not yet recruiting patients) | A pilot trial to define the relevant immune checkpoints expressed on metastatic prostate cancer circulating tumor cells (CTC) | Primary: percent expression of immune checkpoint markers on CTCs Secondary: changing prevalence of immune checkpoint biomarkers on CTCs over time in a longitudinal analysis of four different populations of men with metastatic prostate cancer, change over time in mutational profiles, androgen receptor variant expression, and immune- and tumor-related RNA signatures in CTC-enriched blood, expression of PD-L1, PD-L2, B7-H3, and CTLA-4 in metastatic tumor tissue obtained by elective CT or ultrasound-guided research biopsies in up to 10 patients and compare this expression percentage with CTC immune checkpoint expression | October 2015, January 2017, 40 |
NCT02225704 (ongoing trial, not recruiting patients) | A phase 2, interventional trial to determine the safety and tolerability of radium-223 administered in combination with enzalutamide in progressive mCRPC | Primary: determine safety Secondary: time to clinical and PSA progression, PSA response, time to first skeletal related event, pain assessment, OS | August 2014, December 2016, 44 |