Radium-223 + Pembrolizumab for Prostate Cancer

No longer recruiting at 1 trial location

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: GnRH agonist

Must not be taking: Antidepressants, Immunosuppressants

Disqualifiers: Small cell carcinoma, Liver metastases, HIV, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 223

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs, radium-223 and pembrolizumab, to determine their safety and effectiveness in treating prostate cancer unresponsive to traditional hormone treatments. Radium-223, a radioactive drug, is administered every four weeks, while pembrolizumab, an immunotherapy drug, is given every three weeks. The trial seeks participants with prostate cancer that has spread to the bones and continues to progress despite previous treatments. Ideal candidates should have a confirmed diagnosis of hormone-resistant prostate cancer and be able to provide biopsy samples of bone metastases. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in prostate cancer treatment.

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

The trial requires a 2-week period without any prior systemic or radiation therapy for prostate cancer before starting the study treatment. If you're on systemic steroid therapy or immunosuppressive therapy, you must stop it 7 days before the trial. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that radium-223 is generally safe for treating prostate cancer that has spread to the bones. In earlier studies, most participants tolerated it well, with serious side effects being rare. Some individuals might experience nausea or diarrhea.

The combination of radium-223 with pembrolizumab, a drug that helps the immune system fight cancer, has also undergone study. Results suggest this combination is safe, with no major unexpected side effects. However, pembrolizumab can sometimes cause tiredness or skin issues, which are usually manageable.

Overall, both treatments have been used before, and the safety data is encouraging. The current study is in a mid-stage trial, indicating that previous research supports the treatments' safety, but more information is being collected to confirm these results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Radium-223 and Pembrolizumab for prostate cancer because it offers a unique dual approach. Unlike traditional treatments like hormone therapy and chemotherapy, Radium-223 directly targets bone metastases by emitting radiation that specifically attacks cancer cells in the bones, which is a common site for prostate cancer spread. Pembrolizumab, on the other hand, is an immunotherapy that boosts the body's immune system to recognize and fight cancer cells more effectively. This combination could potentially enhance the overall effectiveness of treatment by both directly targeting the cancer and empowering the immune system to combat it.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

In this trial, participants will receive either Radium-223 alone or a combination of Radium-223 and Pembrolizumab. Studies have shown that Radium-223 can help men with prostate cancer that doesn't respond to hormone therapy and has spread to the bones. It can delay the first bone-related symptoms and improve quality of life. Research indicates that patients receiving Radium-223 live for about 15.7 months on average. Some trials found that combining Radium-223 with Pembrolizumab resulted in no unexpected side effects, but this combination did not significantly improve survival or slow disease progression compared to Radium-223 alone. The evidence suggests that while Radium-223 is effective for prostate cancer with bone involvement, the additional benefit of adding Pembrolizumab remains uncertain. ^{1 2 4 6 7}

Who Is on the Research Team?

Atish Choudhury, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to hormone therapy can join. They must have had a biopsy confirming adenocarcinoma, show cancer progression, and have metastatic disease visible on bone scans. Participants need good organ function, an ECOG performance status of 0 or 1 (fully active or restricted in physically strenuous activity but ambulatory), and agree to use contraception.

Inclusion Criteria

My prostate cancer diagnosis was confirmed through a tissue examination.

Agreement to use adequate contraception

Ability to understand and sign informed consent document

Exclusion Criteria

I meet the specific health and treatment history criteria for the study.

I have previously received treatment with radium-223 or PD-1/PD-L1/PD-L2 blockers.

My prostate cancer is mainly small cell type.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Radium-223 every 4 weeks and Pembrolizumab every 3 weeks

8 weeks

Radium-223: 2 visits (in-person), Pembrolizumab: 3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

22.4 months

Visits every cycle

Long-term follow-up

Participants are followed up for overall survival

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Radium-223

Trial Overview The trial is testing the combination of Radium-223 (a radioactive drug) with Pembrolizumab (an immunotherapy drug) for safety and effectiveness in treating castration-resistant prostate cancer that has spread to bones.

How Is the Trial Designed?

Group I: Radium-223 Experimental Treatment 1 Intervention

\- Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose

Group II: Pembrolizumab Plus Radium-223 Experimental Treatment 2 Interventions

* Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose * Pembrolizumab will be administered intravenously every 3 weeks at a pre-determined dose Radium-223 will be halted after 3 doses. Once radiographic progressive disease occurs, the last 3 doses of radium will be given.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38552171/

Randomized Phase II Study Evaluating the Addition ... - PubMed In a randomized phase II study, we assessed the effect of R223+P compared with R223 on tumor immune infiltration, safety, and clinical outcomes in patients ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.6_suppl.98

Randomized phase II study evaluating the addition of ... This study revealed that R233 + pem did not result in unexpected AEs, but did not lead to prolonged rPFS or OS compared to R223 alone.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11148544/

Randomized Phase II Study Evaluating the Addition of ... This first-in-human, randomized trial demonstrates that combining radium-223 with pembrolizumab does not significantly impact the tumor microenvironment in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02861573

NCT02861573 | Study of Pembrolizumab (MK-3475) ... The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combination therapy in participants with metastatic castration ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2017-01181

Pembrolizumab and Radium Ra 223 Dichloride in Treating ... This randomized phase II trial studies how well pembrolizumab and radium Ra 223 dichloride work in treating patients with castration-resistant prostate ...

6. aacrjournals.org aacrjournals.org/cancerimmunolres/article/12/6/704/745450/Randomized-Phase-II-Study-Evaluating-the-Addition

Randomized Phase II Study Evaluating the Addition of ... This first-in-human, randomized trial demonstrates that combining radium-223 with pembrolizumab does not significantly impact the tumor microenvironment.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2588931125001725

Radium-223 in Men with Metastatic Castration-resistant ... According to the pivotal ALSYMPCA clinical trial, Ra-223 was found to prolong the time to first symptomatic skeletal event, improve quality of life or delay its ...