Nivolumab + Radiation + Hormone Therapy for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Short-term ADT

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune disease, HIV/AIDS, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for prostate cancer. Researchers aim to determine if the investigational drug nivolumab (Opdivo), combined with high-dose radiation and hormone therapy (androgen deprivation therapy or ADT), can safely and effectively slow prostate cancer progression. It targets men diagnosed with aggressive prostate cancer who have not yet received treatment. Participants must be prepared to undergo radiation treatment at Moffitt Cancer Center. The study seeks to provide insights into more effective management and treatment of prostate cancer. As a Phase 1/Phase 2 trial, this research focuses on understanding the treatment's function in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in prostate cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before joining the study.

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

Research has shown that nivolumab, when combined with other treatments, is generally well-tolerated. In studies where nivolumab was used with hormone therapy (ADT) and high-dose radiation, it proved safe. Patients in these studies did not experience any unexpected severe side effects.

For the radiation component, both brachytherapy (a type of internal radiation) and external beam radiation therapy (EBRT) have proven effective and safe for prostate cancer. Common side effects of radiation can include bowel issues or tiredness, but these are usually manageable.

Overall, these treatments have been safely used in other contexts and are being tested together to ensure they remain well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for prostate cancer, which typically involve hormone therapy alone, the combination of nivolumab with radiation and hormone therapy offers a unique approach. Nivolumab is an immunotherapy drug that works by enhancing the body's immune system to target and destroy cancer cells, which is different from traditional therapies that primarily aim to reduce hormone levels. Researchers are excited about this treatment because it not only combines different therapeutic approaches but also leverages the body's natural defenses, potentially leading to more effective and lasting cancer control. This innovative combination could provide new hope for patients by improving outcomes beyond what is achievable with current treatments.

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

Research has shown that combining nivolumab, a type of medication, with radiotherapy can improve outcomes for prostate cancer patients. In this trial, participants will receive a combination of nivolumab, HDR brachytherapy, and external beam radiation therapy (EBRT) following androgen deprivation therapy (ADT). One study found that 90.3% of patients who received both nivolumab and radiotherapy did not experience a return of cancer signs after 2 years, compared to 75% in past studies without this combination. Brachytherapy, a form of internal radiation, effectively treats prostate cancer that hasn't spread, often extending patient survival. EBRT is another proven treatment with good long-term survival rates. Overall, using these treatments together in this trial may better control the progression of prostate cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Kosj Yamoah, M.D., Ph.D.

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer (Grade Group 5, Gleason grade 9 or 10) who are receiving their first treatment and have a good performance status. They must be able to follow the study procedures for its duration, have normal organ function, agree to use contraception if necessary, and not donate sperm during the study.

Inclusion Criteria

I am fully active or can carry out light work.

My prostate cancer is aggressive (Grade Group 5) with a high Gleason score.

I have a confirmed diagnosis of prostate cancer and am starting my first treatment.

Exclusion Criteria

I am not allergic to any of the drugs or their components used in this study.

I do not have any uncontrolled illnesses like infections or heart problems.

Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBVsAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run In

An initial set of participants will be enrolled to determine the rate of dose limiting toxicity of nivolumab

12 weeks

Combination Therapy

Participants receive nivolumab, HDR brachytherapy, and external beam radiation therapy

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Androgen Deprivation Therapy
• Brachytherapy
• External Beam Radiation Therapy
• Nivolumab

Trial Overview The trial is testing how safe and effective nivolumab (Opdivo™) is when combined with high-dose radiation therapy and hormone therapy in delaying prostate cancer progression. Participants will receive this combination as part of their initial treatment.

How Is the Trial Designed?

Group I: Combination Therapy Experimental Treatment 4 Interventions

Post androgen deprivation therapy (ADT), participants will receive nivolumab, HDR brachytherapy and external beam radiation therapy, followed by a 2 year follow-up period.

Androgen Deprivation Therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Recurrent prostate cancer

Approved in United States as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Recurrent prostate cancer
• Localized prostate cancer

Approved in Canada as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Recurrent prostate cancer
• Localized prostate cancer

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Androgen deprivation therapy (ADT) is essential for managing metastatic prostate cancer, primarily through gonadal suppression, and has shown promise in improving quality of life without compromising oncologic efficacy, especially with intermittent ADT.

Neoadjuvant ADT has been proven to enhance outcomes for high-risk patients undergoing radiotherapy, but it does not benefit those opting for radical prostatectomy, highlighting the need for further research in lower-risk localized disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of androgen deprivation therapy in the management of prostate cancer. Cooperberg, MR., Small, EJ., D'Amico, A., et al.[2017]

Androgen deprivation therapy (ADT) is effective for managing symptoms of prostate cancer but can lead to significant side effects that worsen over time, and it does not improve survival in men with localized disease.

Neoadjuvant ADT combined with external beam radiation has been shown to enhance survival in men with locally advanced prostate cancer, while immediate adjuvant ADT does not provide benefits for most men after radical prostatectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The timing and extent of androgen deprivation therapy for prostate cancer: weighing the clinical evidence. Ginzburg, S., Albertsen, PC.[2019]

In a study of 37 men with intermediate- or high-risk localized prostate cancer, a combination of 6 months of androgen-deprivation therapy (ADT) with abiraterone acetate and radiation therapy resulted in a 55% rate of undetectable prostate-specific antigen (PSA) levels at 12 months, indicating effective disease control.

The treatment was associated with manageable toxicity, primarily grade 3 hypertension in 32% of patients, and 81% of participants experienced testosterone recovery within a median time of 9.2 months, suggesting a favorable impact on quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Radiation Therapy and Short-Term Androgen Blockade With Abiraterone Acetate Plus Prednisone for Men With High- and Intermediate-Risk Localized Prostate Cancer. Koontz, BF., Hoffman, KE., Halabi, S., et al.[2021]

Androgen deprivation therapy combined with radiation therapy is a standard treatment for intermediate to high-risk localized and locally advanced prostate cancer, showing effective management of the disease.

Emerging hormonal therapies are being explored for their potential benefits in earlier stages of prostate cancer, particularly in combination with radiation, highlighting a promising area of research for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next Generation of Androgen Deprivation Therapy Combined With Radiotherapy for N0 M0 Prostate Cancer. Barata, P., Layton, J., Lewis, B., et al.[2021]

In a study of 373 intermediate-risk prostate cancer patients treated with radiotherapy over 14 years, those aged 70 or younger who received radiotherapy alone had a higher risk of biochemical failure compared to those who received combined radiotherapy and androgen deprivation therapy (ADT).

The results suggest that short-term ADT may be beneficial for younger patients with favorable intermediate-risk prostate cancer, as it improved biochemical relapse-free survival from 82.1% to 94.0% compared to radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy with or without androgen deprivation therapy in intermediate risk prostate cancer? Amit, U., Lawrence, YR., Weiss, I., et al.[2020]

In a study of 585 high-risk prostate cancer patients treated with high-dose external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT), a biopsy Gleason score (bGS) of 8 to 10 was identified as the strongest predictor of biochemical relapse-free survival (bRFS), distant metastases-free survival (DMFS), and prostate cancer-specific mortality (PCSM).

The study found that the duration of ADT did not significantly impact patient outcomes, highlighting the importance of tumor characteristics over treatment length in predicting survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. Tendulkar, RD., Reddy, CA., Stephans, KL., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9098556/

The 45-month therapy outcomes of permanent seed ... In prostate cancer patients, permanent seed implantation using iodine-125 seeds resulted in similar biochemical recurrence-free survival to ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1687850725002572

Meta-analysis of treatment effects for localized prostate ... The effect of BT seed implantation in treating localized prostate cancer is better than that of EBRT. The 5-year overall survival rate of patients is higher.

3. thegreenjournal.com thegreenjournal.com/article/S0167-8140(23)89749-3/fulltext

The prognosis of patients with prostate cancer receiving ... We study a relationship between prostate volume (PV) and prognosis in 6721 prostate cancer patients treated by permanent seed implantation (PI)

4. emedicine.medscape.com emedicine.medscape.com/article/453349-overview

Brachytherapy (Radioactive Seed Implantation Therapy) in ... HDR combined with external beam radiotherapy was an effective and safe treatment for localized prostate cancer. Pelvic irradiation was suggested ...

5. americanbrachytherapy.org americanbrachytherapy.org/resources/prostate-seeds/

Prostate Seeds Prostate Brachytherapy Seed implants, also known as Low-dose-rate brachytherapy (LDR-BT) is a highly effective minimally invasive treatment for organ-confined ...