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

44 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the safety, tolerability, and effectiveness of the investigational drug nivolumab (Opdivo™) in combination with high dose radiation. Investigators also want to see if these study drugs help to delay the progression of prostate cancer.

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.

What data supports the effectiveness of the treatment Nivolumab + Radiation + Hormone Therapy for Prostate Cancer?

Androgen deprivation therapy (ADT) combined with radiation therapy is a standard treatment for intermediate- and high-risk localized prostate cancer, showing improved survival in locally advanced cases. Newer hormonal therapies are being explored for their potential to enhance outcomes when used with radiation therapy in early stages of prostate cancer. ^{1 2 3 4 5}

Is the combination of Nivolumab, radiation, and hormone therapy safe for humans?

Hormone therapy (also known as androgen deprivation therapy or ADT) combined with radiation therapy is commonly used for prostate cancer, but it can have significant side effects, especially with long-term use. These side effects can include issues related to low testosterone levels. While these treatments are generally considered safe, they do come with potential risks that should be discussed with a healthcare provider. ^{1 5 6 7 8}

How is the treatment of Nivolumab combined with radiation and hormone therapy unique for prostate cancer?

This treatment is unique because it combines Nivolumab, an immunotherapy drug that helps the immune system fight cancer, with traditional hormone therapy and radiation, potentially offering a new approach for prostate cancer that may enhance the effectiveness of existing treatments. ^{1 3 5 9 10}

Research Team

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

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria

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

Provision of signed and dated informed consent form

Stated willingness to comply with all study procedures and availability for the duration of the study

I am fully active or can carry out light work.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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]

References

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

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

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

Next Generation of Androgen Deprivation Therapy Combined With Radiotherapy for N0 M0 Prostate Cancer. [2021]

3. Italy pubmed.ncbi.nlm.nih.gov

The evolving role of androgen deprivation therapy in the management of prostate cancer. [2017]

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

Radiotherapy with or without androgen deprivation therapy in intermediate risk prostate cancer? [2020]

5. United States 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. [2021]

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

Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. [2020]

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

Radiotherapy and short-term androgen deprivation for localized prostate cancer. [2022]

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

Survival benefit associated with adjuvant androgen deprivation therapy combined with radiotherapy for high- and low-risk patients with nonmetastatic prostate cancer. [2007]

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

Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer: The EXTEND Phase 2 Randomized Clinical Trial. [2023]

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

Optimization of the Radiation Management of High-Risk Prostate Cancer. [2018]