Radiation and Hormone Therapy for Prostate Cancer

(OCEAN Trial)

Overseen By Alan Dal Pra, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Miami

Must be taking: Androgen suppression

Must not be taking: Androgen deprivation, Chemotherapy

Disqualifiers: Bone metastasis, Visceral metastasis, 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

Compensation: Varies

Number of Visits: Unknown

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new methods to manage prostate cancer by combining radiation therapy with hormone therapy, also known as Androgen Deprivation Therapy (ADT). The goal is to better control the cancer and enhance patients' quality of life by targeting specific lymph nodes and using advanced imaging techniques. Men with prostate cancer who have no more than five cancer spots in specific areas below the diaphragm and have previously responded to pelvic radiation might be suitable candidates for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not have had androgen deprivation therapy or chemotherapy in the three months prior to the study.

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

Research has shown that treatments like androgen deprivation therapy (ADT) are generally safe. Over 90% of patients experience a decrease in prostate-specific antigen levels, indicating a response to prostate cancer. Common side effects include hot flashes and tiredness.

For drugs that block androgen receptors, studies indicate similar safety, whether used alone or with ADT. Patients might experience side effects like tiredness and nausea, but these are usually manageable.

Para-aortic radiation therapy (PA-RT) is also well-tolerated, with low levels of side effects reported. Patients often maintain good disease control for up to two years after treatment. Overall, these treatments appear safe, though some side effects can occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for prostate cancer involve either surgery, radiation, or hormone therapy that aims to reduce androgen levels, which fuel cancer growth. However, this new approach is unique because it combines androgen deprivation therapy (ADT) and an androgen receptor signaling inhibitor (ARSI) with targeted para-aortic radiation therapy (PA-RT). This combination targets cancer cells more precisely while simultaneously cutting off their hormonal fuel, potentially improving effectiveness and reducing side effects. Researchers are excited about this treatment because it could offer a more comprehensive attack on cancer cells by integrating systemic hormone therapy with a focused radiation approach.

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

Research has shown that treatments for prostate cancer, such as androgen deprivation therapy (ADT), can extend patient survival and lower prostate-specific antigen (PSA) levels. In this trial, participants will receive a combination of ADT and an androgen receptor signaling inhibitor (ARSI), including newer drugs like enzalutamide and abiraterone, which reduce PSA levels more effectively than ADT alone. Participants will also undergo para-aortic radiation therapy (PA-RT), which has yielded promising results, with 83.4% of patients experiencing no cancer progression for two years. Together, these treatments offer strong potential for controlling prostate cancer and improving patient outcomes. ^{2 6 7 8 9}

Who Is on the Research Team?

Benjamin J Rich, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

Men with prostate cancer that has spread to a limited number of spots in the lymph nodes may join this trial. They should be fit for hormone therapy and radiation, and have had PSMA PET/CT scans showing disease progression.

Inclusion Criteria

Willingness to fill out quality of life and psychosocial forms

My prostate cancer responds to hormonal therapy.

My lymph node tumor is smaller than 5 cm.

Exclusion Criteria

I am unable to make medical decisions for myself.

My cancer has a large tumor over 5 cm in size.

No staging with PSMA PET/CT scan

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Systemic Therapy

Participants undergo up to six months of systemic androgen deprivation therapy (ADT) and Androgen receptor signaling inhibitor (ARSI)

24 weeks

Radiation Therapy

Participants receive five weeks of para-aortic radiation therapy

5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and quality of life assessments

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Androgen Deprivation Therapy
• Androgen Receptor Signaling Inhibitor
• Para Aortic Radiation Therapy

Trial Overview

The study is testing if targeting para-aortic lymph nodes with proton or photon radiation, alongside hormone suppression therapy and an androgen receptor signaling inhibitor, can better control prostate cancer while maintaining quality of life.

How Is the Trial Designed?

Group I: PSMA-Guided PA-RT Group Experimental Treatment 4 Interventions

Participants in this group will undergo up to six months of systemic androgen deprivation therapy (ADT) and Androgen receptor signaling inhibitor (ARSI). During system therapy, participants will undergo five weeks of para-aortic radiation therapy. Total participation duration is up to five years.

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?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Published Research Related to This Trial

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 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 94 prostate cancer patients, those who received combined androgen deprivation therapy (ADT) and radiation therapy showed significantly lower levels of prostate-specific antigen (T-PSA) and vascular endothelial growth factor (VEGF), indicating better disease control compared to those who only received radiation therapy.

The combined treatment group also experienced longer progression-free survival (mPFS) and overall survival (OS), highlighting the efficacy of combining ADT with radiotherapy in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Prognostic Factors of Androgen Deprivation Therapy Combined with Radiation Therapy for Prostate Cancer. Zeng, S., Guan, G., Qin, Q., et al.[2022]

Androgen deprivation therapy (ADT) significantly enhances biochemical control when combined with dose-escalated radiation therapy (RT) for prostate cancer, as supported by recent phase III studies.

There is now randomized evidence supporting the use of ADT alongside RT in patients who have undergone prostatectomy, highlighting its ongoing importance in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of Hormonal Therapy to Augment Radiation Therapy in Prostate Cancer: An Update. Kauffmann, G., Liauw, SL.[2018]

Androgen receptor signaling blockade is a key targeted therapy for metastatic prostate cancer, with hormonal therapies significantly improving treatment outcomes, especially when combined with radiotherapy.

Recent clinical trials and studies on the biology of androgen receptor signaling and DNA repair mechanisms are crucial for optimizing the sequencing of androgen deprivation therapy and radiotherapy, potentially leading to new treatment strategies for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms, Challenges, and Opportunities in Combined Radiation and Hormonal Therapies. Coulter, JB., Song, DY., DeWeese, TL., et al.[2022]

Androgen deprivation therapy (ADT) is commonly used alongside radiotherapy to treat prostate cancer, and understanding the biology of the androgen axis can enhance the effectiveness of these combined treatments.

Recent approvals of new drugs necessitate further pre-clinical and clinical studies to explore their potential benefits when used in conjunction with radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The androgen receptor for the radiation oncologist. Quero, L., Rozet, F., Beuzeboc, P., et al.[2015]

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]

Men with high-risk localized prostate cancer may experience improved overall survival and increased disease-free and metastasis-free survival when treated with second-generation anti-androgens like abiraterone acetate alongside androgen deprivation therapy during radiation treatment.

The addition of these potent androgen receptor inhibitors may help overcome resistance to standard androgen deprivation therapy and enhance the effectiveness of radiation by inhibiting DNA repair mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second generation anti-androgens and androgen deprivation therapy with radiation therapy in the definitive management of high-risk prostate cancer. Wang, EC., Lee, WR., Armstrong, AJ.[2023]

Androgen deprivation therapy (ADT) is commonly used for prostate cancer treatment, but its use in certain situations, like low-risk disease or with definitive radiotherapy, lacks strong evidence of benefit.

Careful patient selection and education about ADT can help reduce unnecessary exposure and manage side effects, potentially improving the quality of life for men undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen deprivation therapy: minimizing exposure and mitigating side effects. Gaztañaga, M., Crook, J.[2019]

Androgen deprivation therapy, often used alongside radiotherapy for localized and advanced prostate cancer, can lead to various side effects affecting multiple body systems, including metabolism, muscles, heart health, brain function, and sexual health.

This review emphasizes the importance of monitoring and managing the toxic effects of androgen deprivation therapy to enhance patient care and reduce these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen deprivation therapy toxicity and management for men receiving radiation therapy. Johnson, ME., Buyyounouski, MK.[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]

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