Radium-223 for Recurrent Prostate Cancer

Overseen By Ravi A Madan, M.D.

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, 5-alpha reductase inhibitors

Disqualifiers: HIV, HBV, HCV, prior chemotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 24 weeks

26 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{1 2 3 6 7}

What 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. ^{1 2 3 8 9}

Research Team

Ravi A Madan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility 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.

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.

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)

Treatment Details

Interventions

• Radium-223

Trial Overview 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.

Participant Groups

Group I: 1 Experimental Treatment 2 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

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Radium-223 dichloride (Ra-223) is an effective treatment for patients with castration-resistant prostate cancer and symptomatic bone metastases, showing a 30% reduction in the risk of death compared to placebo.

Ra-223 is considered to have low toxicity, making it a safe option for patients, and it has been approved by both the FDA and EMA for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Alpha emitter radium-223 dichloride: new therapy in castration-resistant prostate cancer with symptomatic bone metastases]. Heinzer, H., König, F., Klutmann, S.[2021]

Radium-223 is the first targeted alpha therapy for patients with castration-resistant prostate cancer and symptomatic bone metastases, offering a new treatment option that requires careful management.

Expert recommendations from 11 nuclear medicine centres across six countries emphasize the importance of structured coordination and communication to optimize radium-223 treatment delivery and enhance patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical recommendations for radium-223 treatment of metastatic castration-resistant prostate cancer. Du, Y., Carrio, I., De Vincentis, G., et al.[2023]

Radium-223 dichloride is the first FDA-approved α-particle emitter for treating metastatic castrate-resistant prostate cancer (CRPC), showing benefits in overall survival and delaying skeletal-related events based on the phase III ALSYMPCA trial.

Current research is exploring Radium-223's effectiveness in earlier stages of cancer, its use in combination with other therapies, and its potential application in treating other cancers that have spread to bone, such as breast and renal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 Therapy for Patients with Metastatic Castrate-Resistant Prostate Cancer: An Update on Literature with Case Presentation. Nguyen, NC., Shah, M., Appleman, LJ., et al.[2020]

Radium Ra-223 dichloride is an effective targeted alpha therapy for treating castration-resistant prostate cancer with symptomatic bone metastases, showing significant survival benefits and delaying skeletal-related events.

This therapy works by selectively accumulating in bone areas with high turnover, where its alpha radiation provides a palliative effect on bone metastases, making it a valuable treatment option for patients with advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer. Poeppel, TD., Handkiewicz-Junak, D., Andreeff, M., et al.[2019]

Radium-223 dichloride is a first-in-class radiopharmaceutical that significantly prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) who have symptomatic bone metastases, based on findings from the Phase III ALSYMPCA trial.

The treatment has a favorable safety profile, with low rates of hematologic adverse events, making it a valuable option for both pre- and post-docetaxel settings in CRPC management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 dichloride for the treatment of bone metastatic castration-resistant prostate cancer: an evaluation of its safety. Nilsson, S.[2018]

Radium Ra 223 dichloride (Ra-223) significantly improves overall survival in patients with castration-resistant prostate cancer and symptomatic bone metastases, with a median survival of 14.0 months compared to 11.2 months for placebo.

Ra-223 is associated with common side effects such as nausea and diarrhea, and it is the first radiopharmaceutical to show a survival advantage in this type of cancer, marking a significant advancement in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium Ra 223 dichloride injection: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Pierce, W., Maher, VE., et al.[2022]

Radium-223 dichloride (Xofigo®) has shown significant survival benefits for prostate cancer patients with bone metastases and a generally favorable safety profile, but its combination with abiraterone and prednisone may increase risks of death and fractures.

A retrospective analysis of approximately 1500 prostate cancer patients revealed that radium-223 can lead to hematological-related side effects, and its safety profile may vary when used with other treatments, highlighting the need for further studies to clarify its toxicological effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Toxicological Profiling of Radium-223 Dichloride for the Treatment of Bone Metastases in Prostate Cancer Using Adverse Event Data. Soldatos, TG., Iakovou, I., Sachpekidis, C.[2020]

In a study of 20 patients with metastatic castrate-resistant prostate cancer (mCRPC) treated with Ra-223 dichloride, those with lower baseline PSA levels and fewer bone lesions had a higher likelihood of a favorable response to therapy, indicating better treatment outcomes.

The study found that 8 out of 20 patients showed improvement in pain and functional status after treatment, while 10 patients did not respond favorably, highlighting the importance of patient selection for optimizing Ra-223 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can bone scans guide therapy with radium-223 dichloride for prostate cancer bone metastases? Gayed, I., Salama, V., Dawood, L., et al.[2023]

Radium-223 dichloride is a unique radiopharmaceutical that uses alpha-emission to effectively treat metastatic castrate resistant prostate cancer (mCRPC) with minimal side effects, particularly low myelosuppression.

Following the successful ALSYMPCA trial, radium-223 was FDA approved in 2013 for patients with mCRPC and symptomatic bone metastases, highlighting its efficacy in prolonging survival in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosing, administration, and safety of radium-223: How I do it. Dan, TD., Doyle, L., Raval, AJ., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Alpha emitter radium-223 dichloride: new therapy in castration-resistant prostate cancer with symptomatic bone metastases]. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Practical recommendations for radium-223 treatment of metastatic castration-resistant prostate cancer. [2023]

3. Egypt pubmed.ncbi.nlm.nih.gov

Radium-223 Therapy for Patients with Metastatic Castrate-Resistant Prostate Cancer: An Update on Literature with Case Presentation. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Radium-223 dichloride for the treatment of bone metastatic castration-resistant prostate cancer: an evaluation of its safety. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Radium Ra 223 dichloride injection: U.S. Food and Drug Administration drug approval summary. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Retrospective Toxicological Profiling of Radium-223 Dichloride for the Treatment of Bone Metastases in Prostate Cancer Using Adverse Event Data. [2020]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Can bone scans guide therapy with radium-223 dichloride for prostate cancer bone metastases? [2023]

9. Canada pubmed.ncbi.nlm.nih.gov

Dosing, administration, and safety of radium-223: How I do it. [2018]