Radium-223 for Recurrent Prostate Cancer
Recruiting in Palo Alto (17 mi)
Overseen byRavi A Madan, M.D.
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Corticosteroids, 5-alpha reductase inhibitors
Disqualifiers: HIV, HBV, HCV, prior chemotherapy, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?Background:
Some men who have been treated for localized prostate cancer with surgery or radiation still show signs of the disease in their blood. This is called biochemically recurrent prostate cancer. Radium-223 is a small molecule. It uses radiation to kill cancer cells and improves survival in advanced prostate cancer. Researchers want to see if it can treat prostate cancer and induced immune changes earlier in the disease when the cancer is only detectable by prostate specific antigen (PSA) in the blood.
Objective:
To learn how Radium-223 affects men with rising PSA but no evidence of cancer on conventional CT or bone scan, but positive findings on PET or molecular imaging in the bones. The primary focus is impact on the immune system with secondary focus on impact on PSA and imaging.
Eligibility:
Men ages 18 and older with prostate cancer who have had surgery and/or radiation, but their PSA is rising even though no disease is visible on routine imaging scans (CT or bone scans). Patients are required to have PET or molecular imaging findings in bones, but not organs (lymph nodes are allowed).
Design:
Participants will be screened with a medical history and physical exam. Their ability to do normal tasks will be reviewed. They will give tissue samples or a report from their doctor about their cancer. They will have blood and urine tests. They will have an electrocardiogram to measure heart function. They will have a scan of their chest and abdomen using radiation or magnetic resonance imaging. They will have a bone scan with injection of Tc99. They will have a positron emission tomography scan with intravenous (IV) injection of 18F-NaF.
Participants will get Radium-223 by IV. For this, a small plastic tube is put into an arm vein. Radium-223 will be given on Day 1 of each cycle (1 cycle = 4 weeks) for up to 6 cycles. Participants will repeat the screening tests during the study. They will also complete Quality of Life Surveys and give stool samples.
After treatment, participants will have long-term follow-up every 6 weeks for the rest of their lives.
Do I need to stop my current medications for the trial?
The trial requires stopping medications that alter PSA levels, like 5-alpha reductase inhibitors (finasteride and dutasteride) and certain alternative therapies. Chronic use of systemic corticosteroids must also be stopped 28 days before starting the trial.
What data supports the effectiveness of the drug Radium-223 for recurrent prostate cancer?
Research shows that Radium-223, also known as Xofigo, can reduce the risk of death by 30% in patients with advanced prostate cancer that has spread to the bones. It is approved for use because it helps patients live longer and delays bone-related problems.
12345Is Radium-223 safe for humans?
Radium-223, also known as Xofigo, is generally considered safe for treating prostate cancer with bone metastases, but it can cause side effects like nausea, diarrhea, and blood-related issues such as anemia (low red blood cell count). It may have increased risks when used with certain other medications, so more studies are needed to fully understand its safety.
12467What makes the drug Radium-223 unique for treating recurrent prostate cancer?
Radium-223 is unique because it is the first targeted alpha therapy for prostate cancer that specifically targets bone metastases, using alpha particles to deliver high-intensity, short-range treatment with minimal side effects. This approach helps prolong survival in patients with metastatic castration-resistant prostate cancer and symptomatic bone metastases.
12489Eligibility Criteria
Men 18+ with prostate cancer, post-surgery or radiation, showing rising PSA levels but no visible disease on CT/MRI scans. They must have positive bone findings on PET scans (lymph nodes allowed), normal organ function tests, and agree to use contraception. Excluded are those with other active cancers within 3 years (except certain skin/bladder cancers), compromised immune systems, recent major surgery or systemic therapy.Inclusion Criteria
My PET scan shows possible prostate cancer spread to bones, but not to organs.
Biochemical progression after definitive surgery or radiation defined as follows:
Histopathological confirmation of prostate adenocarcinoma confirmed in either the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, or Walter Reed National Military Medical Center prior to enrollment. If no pathologic specimen is available, participants may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
+17 more
Exclusion Criteria
I have not had major surgery in the last 28 days.
My PET scan shows signs of internal organ disease.
Serious intercurrent medical illness that, in the judgement of the investigator, would interfere with participant's ability to carry out the treatment program.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive Radium-223 by IV every 4 weeks for up to 6 cycles
24 weeks
6 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
Long-term
Every 6 weeks (in-person)
Participant Groups
The trial is testing Radium-223's effect on biochemically recurrent prostate cancer that's detectable only by PSA in the blood and not by standard imaging. It examines how this treatment impacts the immune system and its influence on PSA levels and imaging results over six cycles of treatment.
1Treatment groups
Experimental Treatment
Group I: 1Experimental Treatment2 Interventions
Participants will receive radium-223 treatment every 4 weeks for up to 6 cycles. 18F-NaF PET scans will be used to assess response in bone.
Radium-223 is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Xofigo for:
- Castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease
🇪🇺 Approved in European Union as Xofigo for:
- Castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Radium-223 Therapy for Patients with Metastatic Castrate-Resistant Prostate Cancer: An Update on Literature with Case Presentation. [2020]Background and Purpose. Radium-223 dichloride (Xofigo®, Bayer HealthCare Pharmaceuticals Inc.) is the first α-particle emitter therapeutic agent approved by the FDA, with benefits in overall survival and delay in symptomatic skeletal event for patients with metastatic castrate-resistant prostate cancer (CRPC). Recent post hoc analyses of the phase III ALSYMPCA trial support the previously established safety profile as well as therapeutic effect and clinical outcome of Radium-223. Currently, Radium-223 is approved as a single agent therapy for metastatic CRPC. Clinical trials are currently investigating Radium-223 in additional clinical settings such as earlier asymptomatic disease and in combination with other agents including hormonal therapeutic agents and immunotherapeutic as well as chemotherapeutic agents. Trials are also ongoing in patients with other primary cancers such as breast cancer, thyroid cancer, and renal cancer metastatic to bone. In this article, the physics and radiobiology, as well as a literature update on the use of Radium-223, are provided along with case presentations, aiming at a better appreciation of research data as well as the assimilation of research data into clinical practice.
Practical recommendations for radium-223 treatment of metastatic castration-resistant prostate cancer. [2023]Radium Ra 223 dichloride (radium-223, Xofigo®) is the first targeted alpha therapy for patients with castration-resistant prostate cancer and symptomatic bone metastases. Radium-223 provides a new treatment option for this setting, but also necessitates a new treatment management approach. We provide straightforward and practical recommendations for European nuclear medicine centres to optimize radium-223 service provision.
EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer. [2019]Radium Ra-223 dichloride (radium-223, Xofigo®) is a targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is the first targeted alpha therapy in this indication providing a new treatment option, with evidence of a significant survival benefit, both in overall survival and in the time to the first symptomatic skeletal-related event. The skeleton is the most common metastatic site in patients with advanced prostate cancer. Bone metastases are a clinically significant cause of morbidity and mortality, often resulting in bone pain, pathologic fracture, or spinal cord compression necessitating treatment. Radium-223 is selectively accumulated in the bone, specifically in areas of high bone turnover, by forming complexes with the mineral hydroxyapatite (the inorganic matrix of the bone). The alpha radiation generated during the radioactive decay of radium-223 produces a palliative anti-tumour effect on the bone metastases. The purpose of this guideline is to assist nuclear medicine specialists in evaluating patients who might be candidates for treatment using radium-223, planning and performing this treatment, understanding and evaluating its consequences, and improving patient management during therapy and follow-up.
[Alpha emitter radium-223 dichloride: new therapy in castration-resistant prostate cancer with symptomatic bone metastases]. [2021]Radium-223 dichloride (Ra-223) is an alpha emitter with low toxicity for the treatment of patients with castrations-resistant prostate cancer (CRPC) and symptomatic bone metastases showing a 30% reduction in the risk of death, as compared to placebo. Because of the favorable physical and chemical characteristics, Ra-223 can be handled easily in daily practice based on interdisciplinary co-operation between urology and nuclear medicine. Ra-223 has been approved under the product name Xofigo® by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
Radium-223 dichloride for the treatment of bone metastatic castration-resistant prostate cancer: an evaluation of its safety. [2018]Approximately 10 - 20% of prostate cancer cases ultimately progress to castration-resistant prostate cancer (CRPC), for which there is a poor prognosis and a therapeutic need. Radium-223 dichloride (radium-223 [Xofigo]) is a first-in-class α-emitting radiopharmaceutical shown to significantly prolong overall survival in patients with CRPC with symptomatic bone metastases and no visceral metastases. Current treatment guidelines recommended it in both pre- and post-docetaxel settings.
Radium Ra 223 dichloride injection: U.S. Food and Drug Administration drug approval summary. [2022]On May 15, 2013, the U.S. Food and Drug Administration (FDA) approved radium Ra 223 dichloride (Ra-223; Xofigo injection; Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no known visceral metastatic disease. The FDA review was based on clinical trial BC1-06, which randomly allocated patients (2:1) to either Ra-223 plus best standard of care (BSoC) or placebo plus BSoC. The primary endpoint was overall survival (OS) with a key secondary endpoint of time to first symptomatic skeletal event (SSE). A statistically significant improvement in OS was demonstrated [HR, 0.70; 95% confidence interval, 0.55-0.88, P = 0.0019]. At the prespecified interim analysis, the median OS durations were 14.0 and 11.2 months in the Ra-223 and placebo arms, respectively. The improvement in OS was supported by a delay in time to first SSE favoring the Ra-223 arm. The most common (>10%) adverse reactions in patients receiving Ra-223 were nausea, diarrhea, vomiting, and peripheral edema. The most common (>10%) hematologic laboratory abnormalities were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Ra-223 is the first α-emitting radiotherapeutic and the first radiopharmaceutical to demonstrate an OS advantage in metastatic prostate cancer.
Retrospective Toxicological Profiling of Radium-223 Dichloride for the Treatment of Bone Metastases in Prostate Cancer Using Adverse Event Data. [2020]Background and Objective: Radium-223 dichloride (Xofigo®) is a calcium mimetic agent approved for the treatment of castration-resistant prostate cancer patients with symptomatic bone metastases and no known visceral metastatic disease. This targeted, α-particle-emitting therapy has demonstrated significant survival benefit accompanied by a favorable safety profile. Nevertheless, recent evidence suggests that its combined use with abiraterone and prednisone/prednisolone may be associated with increased risk of death and fractures. While the precise pathophysiologic mechanisms of these events are not yet clear, collecting evidence from more clinical trials and translational studies is necessary. The aim of our present study is to assess whether accessible sources of patient outcome data can help gain additional clinical insights to radium-223 dichloride's safety profile. Materials and Methods: We performed a retrospective analysis of cases extracted from the FDA Adverse Event Reporting System and characterized side effect occurrence by using reporting ratios. Results: A total of ~1500 prostate cancer patients treated with radium-223 dichloride was identified, and side effects reported with the use of radium-223 dichloride alone or in combination with other therapeutic agents were extracted. Our analysis demonstrates that radium-223 dichloride may often come with hematological-related reactions, and that, when administered together with other drugs, its safety profile may differ. Conclusions: While more prospective studies are needed to fully characterize the toxicological profile of radium-223 dichloride, the present work constitutes perhaps the first effort to examine its safety when administered alone and in combination with other agents based on computational evidence from public real-world post marketing data.
Can bone scans guide therapy with radium-223 dichloride for prostate cancer bone metastases? [2023]Radium-223 dichloride (Ra-223 Xofigo) has recently been approved as an addition to the host of available therapies in the USA as a treatment option for metastatic castrate-resistant prostate cancer (mCRPC) with bone metastases. This study describes our initial experience in patients treated with Ra-223 dichloride. It attempts to optimize patients' selection for the best outcome from Ra-223 dichloride therapy.
Dosing, administration, and safety of radium-223: How I do it. [2018]Radium-223 dichloride is a first-in-class bone-directed radiopharmaceutical that has been shown to prolong survival in men with metastatic castrate resistant prostate cancer (mCRPC). Unlike other radiopharmaceuticals, radium-223 uniquely uses alpha-emission to deliver high intensity, short range cytoxic treatments resulting in minimal myelosuppression. Following the results of the ALSYMPCA trial, radium-223 (Xofigo) was FDA approved in the United States in May 2013 and approved by Health Canada in December 2013 for the treatment of mCRPC with symptomatic bone metastases and no visceral disease. This 'How I do it' article describes the background of radium 223 as well as the methods and techniques that our institution uses for safe and effective administration and notes the subtle differences when administering the drug in Canada.