Nivolumab + Radium-223 for Prostate Cancer

(Rad2Nivo Trial)

Overseen By Braydon Kener

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of Utah

Must not be taking: Immunosuppressants

Disqualifiers: Autoimmune, Cardiovascular, HIV, Hepatitis, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for men with advanced prostate cancer that has spread to the bones and does not respond to standard hormone therapy. It combines Nivolumab, an immune-boosting drug, with Radium-223, which targets bone cancer. The goal is to determine if this combination can better manage the cancer and improve quality of life. Men with hormone-resistant prostate cancer that has caused bone symptoms might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

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.

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

Research has shown that radium-223 is generally safe. In one study, it helped patients with advanced prostate cancer live longer and improved their quality of life. It is already approved for patients with cancer that has spread to the bones, supporting its safety in similar situations.

Nivolumab boosts the immune system to fight cancer and has been safely used in other types of cancer.

Although specific data on the safety of using radium-223 and nivolumab together is not yet available, each has been shown to be safe individually. This trial aims to determine their safety and effectiveness when used together. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining Nivolumab with Radium-223 for prostate cancer because it offers a novel approach compared to standard treatments like hormone therapy, chemotherapy, and surgery. Nivolumab is an immunotherapy drug that works by unleashing the immune system to attack cancer cells, unlike traditional treatments that directly target the cancer cells themselves. Radium-223, on the other hand, is a type of radiopharmaceutical that specifically targets bone metastases, which are common in advanced prostate cancer, delivering radiation directly to the cancer sites while sparing most healthy tissue. This combination has the potential to enhance the overall effectiveness by both boosting the immune response and directly targeting cancer in the bones.

What evidence suggests that this treatment might be an effective treatment for prostate cancer?

Studies have shown that radium-223 can help patients with advanced prostate cancer that has spread to the bones live longer and feel better. This trial evaluates how well radium-223 works when combined with another treatment called nivolumab. This combination might enhance the body's ability to fight cancer. Previous patients treated with radium-223 experienced good results in terms of safety and effectiveness. By combining these treatments, the goal is to leverage their strengths to better combat prostate cancer that has spread. Early research suggests this combination could be promising for improving patient outcomes. ^{1 2 3 4 6}

Who Is on the Research Team?

Benjamin Maughan, MD

Principal Investigator

Huntsman Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04109729

Study of Nivolumab in Combination w Radium-223 in Men ... We hypothesize that radium-223 plus nivolumab will result in significant, favorable tumor microenvironment alterations leading to significant clinical activity ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1040842825002070

A new era for radium-223? Optimizing treatment by ... 2019). Conversely, the recent results of the PEACE-3 phase III trial, showed improved survival outcomes in patients treated with enzalutamide plus radium-223, ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5050

Real-world safety and effectiveness of radium-223 (223Ra) ... 223 Ra improved overall survival (OS) and quality of life and demonstrated a favorable safety profile in pts with mCRPC in the phase 3 ALSYMPCA trial.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9812947/

Real-world effectiveness, long-term safety and treatment ... Radium-223 dichloride (223Ra) is an α-emitter approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) with bone metastases, ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-01957

Nivolumab and Radium-223 for the Treatment of Metastatic ... This phase I trial studies how well nivolumab and radium-223 work in treating patients with prostate cancer that grows and continues to spread.

6. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1460212/full

Treatment intensification with radium-223 plus ... Data from the Surveillance Epidemiology and End Results (SEER) program from 2013 to 2019 indicate a 5-year relative survival rate of 34% for ...