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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Radium-223, known for aiding advanced prostate cancer, can be effective earlier, specifically when cancer is detectable only through certain blood markers (PSA) and special scans. The main goal is to assess how Radium-223 affects the immune system and its impact on PSA levels and imaging results. Men who have undergone prostate cancer treatment, such as surgery or radiation, and now have a rising PSA but no visible cancer on standard scans might be suitable candidates. Participants will receive Radium-223 through intravenous treatments every four weeks for up to six cycles, with regular check-ups and tests. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in prostate cancer treatment.

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.

Is there any evidence suggesting that Radium-223 is likely to be safe for humans?

Research shows that Radium-223 is generally safe for patients with advanced prostate cancer. Studies have used it safely in men whose cancer has spread to their bones. Its approval for a similar condition further supports its safety. Most patients experience only mild side effects, such as nausea, diarrhea, or fatigue, while serious side effects remain rare. This suggests that Radium-223 could be safe for men with rising PSA levels but no visible cancer on regular scans. However, individual reactions can differ, so discussing the risks with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Radium-223 is unique because it specifically targets bone metastases in recurrent prostate cancer by emitting alpha particles, which cause localized damage to cancer cells in the bone. Unlike traditional treatments such as hormone therapy or chemotherapy, which can affect the entire body and lead to significant side effects, Radium-223's targeted approach minimizes damage to surrounding healthy tissue. Researchers are excited about this treatment because it not only has the potential to extend survival but also improves quality of life by reducing bone pain and limiting systemic side effects.

What evidence suggests that Radium-223 might be an effective treatment for recurrent prostate cancer?

Research shows that Radium-223 can help men with advanced prostate cancer live longer. One study found that completing five or more treatments with Radium-223 increased survival by two to five times. Another study showed that Radium-223 extended life from 11.3 months to 14.9 months and delayed bone problems by several months. In this trial, participants will receive Radium-223 treatment every 4 weeks for up to 6 cycles, with 18F-NaF PET scans assessing response in bone. Although previous research focuses on advanced cancer, it suggests that Radium-223 might also benefit patients with earlier-stage cancer by targeting cancer in the bones, as seen through special imaging tests. Overall, Radium-223 appears promising in improving outcomes for prostate cancer, especially when it has spread to the bones. ^{2 6 7 8 9}

Who Is on the Research Team?

Ravi A Madan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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-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 (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]

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]

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]

Citations

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sciencedirect.com

sciencedirect.com/science/article/pii/S2588931125001725

Radium-223 in Men with Metastatic Castration-resistant ...

Completion of five or more cycles of Ra-223 was associated with a two- to five-fold increase in overall survival. Ra-223 was well tolerated, with a safety ...

2.

thelancet.com

thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00170-0/fulltext

Clinical outcomes and treatment patterns in REASSURE

In the 6 months after completion of radium-223 therapy, 214 (15%) patients had grade 3/4 haematological toxicities. Eighty patients (5%) had ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6445613/

Ra-223 Treatment for Bone Metastases in Castrate ...

The phase 3 ALSYMPCA trial (NCT00699751) showed that Ra-223 prolonged survival (14.9 vs. 11.3 mo; P<0.0001) and time to first SRE (median, 15.6 vs. 9.8 mo; 95% ...

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO-25-00131

The RAVENS Phase II Randomized Trial

Most SABR MDT/Ra223 patients (87%) received six cycles of Ra223. The median PFS was 11.8 months with SABR MDT and 10.5 months with SABR MDT/ ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT04521361

NCT04521361 | A Study to Assess How Radium-223 ...

In this study researcher want to gain more information on how the study drug (radium-223) is distributed in the bone, particularly in the tumor free bone in ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6572036/

Retrospective Toxicological Profiling of Radium-223 ...

Radium-223 dichloride (Xofigo ® ) is a calcium mimetic agent approved for the treatment of castration-resistant prostate cancer patients with symptomatic bone ...

7.

aetna.com

aetna.com/cpb/medical/data/800_899/0874.html

Radium Ra 223 Dichloride (Xofigo)

The authors concluded that they have shown that Ra-223 dichloride can be safely administered in a patient with hormone-refractory bone metastasis from breast ...

8.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.119

Patient characteristics and safety of radium-223 dichloride ...

Here, we present data on the safety and effectiveness of Ra-223 in patients with mCRPC and symptomatic bone metastases under routine clinical practice in ...

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04597125

NCT04597125 | Investigation of Radium-223 Dichloride ...

Radium-223 dichloride will be given as an infusion into one of the veins on Day 1 of each 4-week cycle for a total of up to 6 cycles. Oral NAH therapy will be ...