Nivolumab + Radium-223 for Prostate Cancer

(Rad2Nivo Trial)

Overseen By Braydon Kener

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of Utah

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

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 24 months

39 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 1, open label, prospective, non-randomized single arm study combining Radium-223 with nivolumab in men with metastatic castration resistant prostate cancer.

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

The trial protocol does not specify if you must stop all current medications. However, there is a washout period required for prohibited medications, which is at least 5 half-lives or as clinically indicated before starting treatment. Please consult with the trial team for specific guidance on your medications.

Will I have to stop taking my current medications?

The trial protocol mentions that if you are taking any prohibited medications, you will need to stop them for a period of at least 5 half-lives (time it takes for the drug's active substance to reduce by half in the body) or as clinically indicated before starting the treatment. However, it does not specify which medications are prohibited, so you should discuss your current medications with the study team.

What data supports the idea that Nivolumab + Radium-223 for Prostate Cancer is an effective treatment?

The available research shows that Radium-223, when used for prostate cancer, improves survival rates in patients with advanced stages of the disease. Although the studies focus on Radium-223 alone, they highlight its effectiveness in increasing overall survival and improving quality of life for patients. This suggests that combining Radium-223 with other treatments like Nivolumab could potentially enhance these benefits, making it a promising option for treating prostate cancer. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Nivolumab + Radium-223 for prostate cancer?

Research shows that Radium-223 can improve survival in patients with advanced prostate cancer that has spread to the bones. This suggests that combining it with other treatments like Nivolumab might also be beneficial. ^{1 2 3 4 5}

What safety data exists for Nivolumab + Radium-223 in prostate cancer treatment?

The provided research does not directly address the safety data for the combination of Nivolumab (Opdivo) and Radium-223 in prostate cancer treatment. However, it includes studies on Radium-223 alone or in combination with other treatments, such as Sipuleucel-T and Atezolizumab, which discuss safety and adverse events. These studies indicate that Radium-223 is associated with improved overall survival in metastatic castration-resistant prostate cancer (mCRPC) but can lead to treatment discontinuation due to adverse events. The safety of Radium-223 in combination with other immunotherapies like Atezolizumab has been evaluated, but specific safety data for the combination with Nivolumab is not provided in the research. ^{2 5 6 7 8}

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

There is safety data available for Radium-223, which has been used in men with prostate cancer that has spread to the bones. Some patients have had to stop treatment due to side effects, but it has been shown to improve survival in these cases. However, specific safety data for the combination of Nivolumab and Radium-223 is not provided in the available research. ^{2 5 6 7 8}

Is the drug Nivolumab a promising treatment for prostate cancer in the trial titled 'Nivolumab + Radium-223 for Prostate Cancer'?

The research articles focus on Radium-223, which is shown to improve survival and quality of life for prostate cancer patients with bone metastases. While Nivolumab is not specifically mentioned in these articles, the combination with Radium-223 could be promising because Radium-223 has proven benefits in treating prostate cancer. ^{2 4 6 9 10}

How is the drug Nivolumab + Radium-223 different from other prostate cancer treatments?

Nivolumab + Radium-223 is unique because it combines an immune checkpoint inhibitor (Nivolumab) with a bone-targeting radiopharmaceutical (Radium-223), which specifically targets bone metastases in prostate cancer. This combination aims to enhance the immune response while directly addressing bone metastases, offering a novel approach compared to traditional treatments like chemotherapy or hormone therapy. ^{2 4 6 9 10}

Research Team

Benjamin Maughan, MD

Principal Investigator

Huntsman Cancer Institute

Eligibility Criteria

This trial is for men over 18 with advanced prostate cancer that has spread to the bones but not to other organs. They must have a certain white blood cell count, hemoglobin level, and liver function; no severe side effects from previous treatments; controlled testosterone levels; and be in fairly good health overall. Men who can father children must use effective birth control.

Inclusion Criteria

Platelet count ≥ 100,000/mm3

I am using or will use effective birth control during and for 7 months after the study.

Absolute neutrophil count (ANC) ≥ 1500/mm3

Exclusion Criteria

You have had a very bad allergic reaction in the past to the study drug or any of its ingredients.

I have not received any live vaccines within the last 4 weeks.

I have another type of cancer, but it won't affect this trial's treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Radium-223 kBq/kg IV every 4 weeks for up to 6 doses and Nivolumab 480 mg IV every 4 weeks for up to 2 years

24 months

Every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue to be monitored for long-term outcomes such as radiographic progression-free survival and PSA progression-free survival

up to 24 months

Treatment Details

Interventions

• Nivolumab

Trial Overview The study tests Nivolumab combined with Radium-223 in an open-label setup where everyone knows what treatment they're getting. It starts with a safety check phase followed by a larger test phase to see how well it works for bone metastasis in prostate cancer.

Participant Groups

Group I: All patients Experimental Treatment 2 Interventions

Radium-223 kBq/kg IV every 4 weeks for up to 6 doses. Nivolumab 480 mg IV every 4 weeks for up to 2 years.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Findings from Research

In a study of 64 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223, the median survival was found to be 12.9 months, indicating its effectiveness in improving survival in routine clinical practice.

Four key factors were identified that significantly influenced survival after radium-223 treatment: no prior chemotherapy, having 5 or fewer bone metastases, baseline alkaline phosphatase levels below 115 U/L, and a positive response in alkaline phosphatase after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Associated With Survival Following Radium-223 Treatment for Metastatic Castration-resistant Prostate Cancer. Wong, WW., Anderson, EM., Mohammadi, H., et al.[2019]

In a study of 32 men with bone-predominant metastatic castration-resistant prostate cancer, the combination of radium-223 and sipuleucel-T led to a significant increase in progression-free survival (39 weeks vs. 12 weeks) and overall survival (not reached vs. 2.6 years) compared to sipuleucel-T alone.

Despite the combination treatment showing lower immune responses (3.2-fold less T-cell response), it resulted in a higher rate of PSA decline (>50% in 31% of patients), suggesting that radium-223 may enhance the clinical effectiveness of sipuleucel-T.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer. Marshall, CH., Fu, W., Wang, H., et al.[2022]

In a study of 318 men with metastatic castration-resistant prostate cancer treated with radium-223, the median overall survival was 11 months, which is shorter than the 14.9 months reported in the ALSYMPCA trial, indicating that real-world outcomes may vary.

Only 42% of patients completed the full treatment course of 6 radium-223 injections, with many receiving only 1 or 2, suggesting that radium-223 is often administered later in the disease progression and in a more diverse patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 Utilization Patterns and Outcomes in Clinical Practice. Taich, L., Zhao, H., Stock, SR., et al.[2023]

In a study of 228 men with metastatic castration-resistant prostate cancer treated with radium 223 (Ra-223), the median overall survival was 11.1 months, with chemotherapy-naïve patients showing better survival (12.3 months) compared to those who had prior chemotherapy (8.1 months).

Ra-223 treatment improved pain scores in 54% of patients and overall quality of life, although the fracture rate was notably high (24%) in patients previously treated with abiraterone and prednisolone, suggesting the need for routine bone health evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimising Radium 223 Therapy for Metastatic Castration-Resistant Prostate Cancer -5-year Real-World Outcome: Focusing on Treatment Sequence and Quality of Life. Jiang, XY., Atkinson, S., Pearson, R., et al.[2021]

In a study of 30 men with bone metastatic castration-resistant prostate cancer (mCRPC), treatment with radium-223 led to a significant decrease in absolute lymphocyte counts, indicating a potential impact on the immune system during therapy.

The therapy also resulted in an increase in T cells expressing costimulatory and inhibitory checkpoint molecules, as well as an increase in immunosuppressive cell subsets, suggesting that radium-223 may influence immune responses in mCRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunophenotyping Reveals Longitudinal Changes in Circulating Immune Cells During Radium-223 Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer. Creemers, JHA., van der Doelen, MJ., van Wilpe, S., et al.[2022]

Radium-223 ((223)Ra) is an FDA-approved treatment for men with castration-resistant prostate cancer (CRPC) who have symptomatic bone metastases and no known visceral metastatic disease, showing increased survival compared to standard care in clinical trials.

While (223)Ra is generally well tolerated with up to 6 injections, common side effects include nausea, diarrhea, and various blood-related issues, indicating the need for further research on its long-term safety and potential use alongside chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 dichloride: a novel treatment option for castration-resistant prostate cancer patients with symptomatic bone metastases. McGann, S., Horton, ER.[2019]

In a study of 75 metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223, those who discontinued treatment due to adverse events had significantly worse progression-free survival (PFS) and overall survival (OS) compared to those who stopped for other reasons.

The likelihood of treatment discontinuation due to toxicity was linked to factors such as the number of previous treatments and baseline blood markers, suggesting that early intervention with Ra-223 may help minimize toxicities and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of radium-223 discontinuation due to adverse events in castration-resistant prostate cancer patients. A retrospective monocentric analysis. Turco, F., Tucci, M., Angusti, T., et al.[2023]

In a phase Ib study involving 45 men with metastatic castration-resistant prostate cancer (mCRPC), the combination of atezolizumab and radium-223 resulted in significant toxicity, with 52.3% of participants experiencing grade 3/4 adverse events, primarily related to atezolizumab.

The treatment showed a low confirmed objective response rate of only 6.8% and a median overall survival of 16.3 months, indicating that while the combination was safe to assess, it did not provide clear additional clinical benefits compared to the individual therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer. Fong, L., Morris, MJ., Sartor, O., et al.[2023]

In a study of 36 patients with bone-metastatic, castration-resistant prostate cancer, radium-223 treatment led to significant reductions in pain scores, particularly when used as second-line and third-line therapy.

While some patients experienced an increase in prostate-specific antigen levels, radium-223 showed early biochemical benefits and was associated with a decrease in alkaline phosphatase levels in chemotherapy-naive patients, with anemia being the most common adverse event at 16.7%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 for metastatic, castration-resistant prostate cancer: A retrospective chart review study of real-world use in a tertiary hospital in Taiwan. Weng, WC., Huang, LH., Tseng, NC., et al.[2022]

Radium-223 is an effective treatment for bone metastatic castration-resistant prostate cancer, improving overall survival and quality of life, as demonstrated in a Phase III randomized placebo-controlled study.

Unlike traditional chemotherapy, radium-223 specifically targets bone metastases and can be administered without complex shielding, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer - role of radium-223. Mukherji, D., El Dika, I., Temraz, S., et al.[2021]

References

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

Factors Associated With Survival Following Radium-223 Treatment for Metastatic Castration-resistant Prostate Cancer. [2019]

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

Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer. [2022]

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

Radium-223 Utilization Patterns and Outcomes in Clinical Practice. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Optimising Radium 223 Therapy for Metastatic Castration-Resistant Prostate Cancer -5-year Real-World Outcome: Focusing on Treatment Sequence and Quality of Life. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Immunophenotyping Reveals Longitudinal Changes in Circulating Immune Cells During Radium-223 Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer. [2022]

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

Radium-223 dichloride: a novel treatment option for castration-resistant prostate cancer patients with symptomatic bone metastases. [2019]

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

Role of radium-223 discontinuation due to adverse events in castration-resistant prostate cancer patients. A retrospective monocentric analysis. [2023]

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

A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer. [2023]

9. Singapore pubmed.ncbi.nlm.nih.gov

Radium-223 for metastatic, castration-resistant prostate cancer: A retrospective chart review study of real-world use in a tertiary hospital in Taiwan. [2022]

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

Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer - role of radium-223. [2021]