Radium-223 + Docetaxel for Prostate Cancer

Recruiting at 73 trial locations

Overseen By Josef Fox, MD

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: LHRH analogues

Must not be taking: 5-alpha-reductase inhibitors

Disqualifiers: Visceral metastases, Active second malignancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 10

Duration: 30 weeks

738 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare any good and bad effects of using radium-223 along with docetaxel chemotherapy treatment versus using docetaxel alone. Earlier studies helped show that the combination is safe, but the combination has not been proven to work better than either drug alone. The goal of this study is to find out if combining docetaxel and radium-223 is better than giving either drug by itself.

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken certain treatments like investigational agents, external beam radiotherapy, or specific supplements within 4 weeks before joining. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Radium-223 and Docetaxel for prostate cancer?

Research shows that Radium-223 can improve survival in prostate cancer patients with bone metastases, and Docetaxel is known to enhance survival in similar cases. Combining these drugs may be safe and effective, as they target both the tumor and bone. ^{1 2 3 4 5}

Is the combination of Radium-223 and Docetaxel safe for humans?

Radium-223 has shown a favorable safety profile when used alone for prostate cancer with bone metastases, but it may cause blood-related side effects. When combined with other drugs, its safety profile can change, and more studies are needed to fully understand its safety in combination with Docetaxel. ^{1 2 5 6 7}

How is the Radium-223 + Docetaxel treatment different from other prostate cancer treatments?

This treatment is unique because it combines Radium-223, a bone-targeting therapy that emits alpha particles to kill cancer cells in the bones, with Docetaxel, a chemotherapy drug that disrupts cancer cell growth. This combination aims to target both the tumor and bone metastases, potentially improving survival in patients with castration-resistant prostate cancer. ^{2 3 4 5 7}

Research Team

Michael Morris, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for males over 18 with progressive prostate cancer, who have not had certain recent treatments or a second active malignancy. They must have normal organ function, agree to birth control measures, and be willing to follow the study protocol.

Inclusion Criteria

Any side effects from my previous treatments are mild.

Willing and able to comply with the protocol, including follow-up visits and examinations

My cancer has grown by 20% or more, or I have new cancer spots since starting treatment.

Exclusion Criteria

I have swelling in my groin, penis, or legs due to cancer.

I haven't taken any experimental cancer treatments or other cancer therapies in the last 4 weeks.

I have severe urinary or rectal symptoms due to my cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive docetaxel chemotherapy with or without radium-223

30 weeks

10 visits (in-person, every 3 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Docetaxel
• Radium-223

Trial Overview The study tests if combining Radium-223 with Docetaxel chemotherapy is more effective than using Docetaxel alone in treating prostate cancer. Participants will receive one of these treatment regimens to compare outcomes.

Participant Groups

Group I: Docetaxel with Radium-223 Experimental Treatment 2 Interventions

Docetaxel 60 mg/m2 will be administered IV every 3 weeks for 10 doses. Radium-223 will be administered at 55 kBq/kg, 6 injections at 6 weeks intervals.

Group II: Docetaxel Experimental Treatment 1 Intervention

Docetaxel 75 mg/m2 will be administered IV every three weeks for 10 doses. Prednisone will be given at a dose of 5mg orally twice daily.

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Findings from Research

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]

The combination of radium-223 and docetaxel was found to be well tolerated in patients with bone-predominant metastatic castration-resistant prostate cancer, with a recommended phase 2 dose established for future studies.

Patients receiving the combination treatment showed a longer median time to progression of prostate-specific antigen levels compared to those on docetaxel alone, suggesting enhanced antitumor activity from the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 in combination with docetaxel in patients with castration-resistant prostate cancer and bone metastases: a phase 1 dose escalation/randomised phase 2a trial. Morris, MJ., Loriot, Y., Sweeney, CJ., et al.[2020]

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]

In a study of 36 patients with castration-resistant prostate cancer and bone metastasis, using Radium-223 (Ra-223) therapy before docetaxel (DOC) resulted in a significantly higher treatment completion rate (94% vs. 52%) and longer progression-free survival (8 months vs. 5 months).

Patients receiving Ra-223 before DOC also experienced longer cause-specific survival (32 months vs. 15 months), suggesting that Ra-223 is more effective and potentially safer when administered prior to DOC therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Radium-223 for Castration-resistant Prostate Cancer With Bone Metastasis Before and After Docetaxel. Okabe, KO., Terada, N., Shirakawa, T., et al.[2022]

In a study involving 921 patients with castration-resistant prostate cancer and symptomatic bone metastases, radium-223 significantly improved health-related quality of life (QOL) compared to placebo, with 29.2% of patients experiencing meaningful improvement in QOL scores versus 18.5% in the placebo group.

Radium-223 not only enhanced survival rates but also resulted in a slower decline in QOL over time, indicating that it provides both therapeutic and quality of life benefits for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study. Nilsson, S., Cislo, P., Sartor, O., 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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Radium-223 in combination with docetaxel in patients with castration-resistant prostate cancer and bone metastases: a phase 1 dose escalation/randomised phase 2a trial. [2020]

3. 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]

4. Greece pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Radium-223 for Castration-resistant Prostate Cancer With Bone Metastasis Before and After Docetaxel. [2022]

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

Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study. [2022]

6. 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]

7. Germany pubmed.ncbi.nlm.nih.gov

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