Hormone Therapy + Radiation for Prostate Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Androgen deprivation therapy

Must not be taking: Anticoagulants

Disqualifiers: Pelvic radiation, Chemotherapy, Anticoagulation, 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

Duration: 2-18 months

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating high-risk prostate cancer by combining hormone therapy (Gonadotropin-releasing Hormone Analog) with radiation. The goal is to determine if fewer hormone treatments—tailored to individual risk factors—can be as effective as more intensive hormone therapy. The study includes three groups: one receives only radiation, another receives hormone therapy plus radiation, and the third receives both along with an additional medication called abiraterone acetate. Men diagnosed with high-risk prostate cancer, particularly those with a high Gleason score or elevated PSA levels, may be suitable candidates for this trial. As a Phase 2 trial, it focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on certain blood thinners like warfarin or heparin unless they can be stopped for treatment-related reasons.

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

Research shows that the treatments in this trial have varying safety levels. Studies confirm that the hormone treatment used is a reliable option for prostate cancer, with about 85% of patients with advanced cancer responding well. However, certain types of these hormone treatments carry a risk of heart-related issues.

Radiation therapy, another part of the trial, generally maintains a good safety record. It can cause some urinary and bowel problems, but these are usually manageable. Shorter courses of radiation tend to have fewer negative effects on daily life.

Abiraterone acetate, another drug in the trial, is associated with a high rate of side effects, with almost all patients experiencing at least one. Despite this, abiraterone often helps prostate cancer patients live longer.

In summary, while these treatments carry some risks, they are mostly well-tolerated and effective in treating prostate cancer. Participants should consider these factors when deciding to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they explore the combination of hormone therapy and radiation in innovative ways. Unlike the standard care that often involves either surgery or hormone therapy alone, these treatments introduce the use of a Gonadotropin-releasing Hormone Analog combined with targeted radiation, and in one arm, the addition of abiraterone acetate. This combined approach could potentially enhance the effectiveness by targeting cancer cells more precisely and reducing their growth. By integrating imaging techniques like PET, CT, or MRI, these treatments also aim to monitor progress more accurately, offering a comprehensive strategy to manage prostate cancer more effectively than current options.

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

Research has shown that androgen deprivation therapy (ADT) is highly effective for prostate cancer, particularly in advanced stages, with about 85% of patients responding well. ADT lowers testosterone levels, which helps shrink tumors that rely on this hormone for growth. In this trial, some participants will receive ADT along with radiation therapy, which uses high-energy rays to target and shrink cancer cells, helping to prevent the cancer from spreading. Another group will receive ADT and radiation therapy with the addition of abiraterone acetate, a medication that can further lower hormone levels and has been shown to extend the lives of patients with advanced prostate cancer. Combining these treatments and adjusting them based on a patient's specific risk may maintain their effectiveness while reducing side effects. ^{4 6 7 8 9}

Who Is on the Research Team?

Carlos E. Vargas, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals with prostate cancer, specifically adenocarcinoma. Participants should be suitable for hormone therapy and radiation, and willing to undergo various imaging tests like CT, MRI, PET scans, as well as provide biospecimens. The study aims to tailor the amount of hormone treatment based on individual risk factors.

Inclusion Criteria

Patients must sign institutional review board (IRB) approved study specific informed consent

Patients must complete all required pre-entry tests

My prostate cancer is confirmed to be high risk.

Exclusion Criteria

I have had radiation therapy to my pelvic area before.

I have been on hormone therapy for prostate cancer for over 6 months.

I do not have active rectal problems like diverticulitis, Crohn's, or ulcerative colitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive risk-based de-escalated hormone therapy (ADT) and radiation therapy. Group I undergoes radiation therapy for 2-6 weeks. Group II receives ADT for up to 12 months and radiation therapy starting on week 8-10. Group III receives ADT with or without abiraterone acetate for up to 18 months and radiation therapy starting on week 8-10.

2-18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at months 3 and 12, then yearly for up to year 5, followed by every 2 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Gonadotropin-releasing Hormone Analog
• Radiation Therapy

Trial Overview The trial is testing a de-escalated (reduced) approach to hormone therapy combined with radiation in treating prostate cancer. It involves using drugs that lower testosterone levels (like LHRH analogs and Zytiga) alongside high-energy treatments aimed at killing cancer cells or shrinking tumors.

How Is the Trial Designed?

Group I: Group III (ADT, radiation therapy, abiraterone acetate) Experimental Treatment 8 Interventions

Patients receive ADT SC or IM with or without abiraterone acetate for up to 18 months in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy to identified areas over 2 - 6 weeks starting on week 8-10 of ADT hormone therapy. Additionally, patients undergo PET, CT or MRI and blood sample collection throughout the study.

Group II: Group II (ADT, radiation therapy) Experimental Treatment 7 Interventions

Patients receive ADT SC or IM for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy to the prostate bed over 2 - 6 weeks starting on week 8-10 of ADT hormone therapy. Additionally, patients undergo PET, CT or MRI and blood sample collection throughout the study.

Group III: Group I (radiation therapy) Experimental Treatment 6 Interventions

Patients undergo radiation therapy to the prostate bed over 2 - 6 weeks. Additionally, patients undergo PET, CT or MRI and blood sample collection throughout the study.

Gonadotropin-releasing Hormone Analog is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as GnRH analog for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in European Union as LHRH analog for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in Canada as GnRH analog for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in Japan as LHRH analog for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In a retrospective study of patients with locally advanced prostate cancer, treatment with radiotherapy (RT) plus LHRH analog triptorelin (monotherapy) showed similar overall survival rates compared to RT plus total androgen block (TAB).

While there was no significant difference in late gastrointestinal and genitourinary toxicities between the two treatment groups, a trend suggested that TAB might offer better progression-free survival, highlighting the importance of considering treatment options that minimize adverse events and maintain quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy Plus Total Androgen Block Versus Radiotherapy Plus LHRH Analog Monotherapy for Non-metastatic Prostate Cancer. Marvaso, G., Viola, A., Fodor, C., et al.[2018]

In a study of 10 intermediate-risk prostate cancer patients, testosterone levels dropped to castration levels within one month of starting LHRH antagonist treatment, but most patients normalized their testosterone levels within 9 months after stopping the treatment.

Despite initial declines in sexual and hormonal function during LHRH antagonist therapy, significant recovery was observed in these functions after treatment, indicating that short-term LHRH antagonist therapy is safe and effective for managing prostate cancer without long-term negative effects on sexual health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recovery of Serum Testosterone Levels and Sexual Function in Patients Treated With Short-term Luteinizing Hormone-releasing Hormone Antagonist as a Neoadjuvant Therapy Before External Radiotherapy for Intermediate-risk Prostate Cancer: Preliminary Prospective Study. Inoue, T., Mizowaki, T., Kabata, D., et al.[2019]

In a phase I study involving patients with advanced prostate cancer, irradiation to the testes was tested as an alternative to standard androgen deprivation treatments, showing that both tested radiation regimens (17 Gy in 2 fractions and 24 Gy in 3 fractions) were well tolerated with minimal toxicity.

Despite the treatment being well tolerated, neither radiation regimen successfully induced castration, as all patients maintained normal testosterone levels during the 11 to 36 months of follow-up, indicating that further research is needed to determine the efficacy of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective phase I study on testicular castration induced by radiation treatment. Faria, S., Cury, F., Souhami, L.[2018]

In a phase III trial involving 415 patients with locally advanced prostate cancer, combining external irradiation with long-term androgen suppression significantly improved 5-year clinical disease-free survival from 40% to 74%.

The addition of androgen suppression also enhanced overall survival rates from 62% to 78%, demonstrating that immediate treatment with an LHRH analogue during and after radiation therapy provides substantial benefits for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Bolla, M., Collette, L., Blank, L., et al.[2022]

Both LNCaP and PC-3 prostate cancer cell lines express LHRH receptors, confirming the potential for goserelin to interact with these cells during treatment.

However, the study found that goserelin did not significantly enhance the effectiveness of radiotherapy on cell survival or viability in vitro, suggesting that the improved clinical outcomes seen with goserelin and radiotherapy may not be due to increased radiosensitivity of prostate cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No supra-additive effects of goserelin and radiotherapy on clonogenic survival of prostate carcinoma cells in vitro. Hermann, RM., Schwarten, D., Fister, S., et al.[2022]

In a study of 318 prostate cancer patients with a median follow-up of 56 months, both radiotherapy combined with GnRHa and radiotherapy combined with bicalutamide showed similar five-year biochemical relapse-free survival rates (85.5% for GnRHa and 88.3% for bicalutamide).

Bicalutamide may be a suitable alternative for patients who prefer to avoid the side effects associated with GnRHa, highlighting the need for further randomized trials to compare these two treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy Plus GnRH Analogue Versus High Dose Bicalutamide: A Case Control Study. Buwenge, M., Deodato, F., Macchia, G., et al.[2020]

In three clinical trials for locally advanced prostate cancer, combining external irradiation with LHRH analogues significantly improved various survival rates, including disease-free and overall survival, with a notable P-value of < 0.001.

The EORTC trial 22863 specifically demonstrated a significant overall survival benefit when using the LHRH analogue goserelin acetate from the start of irradiation for three years, while the RTOG trial 85-31 showed survival improvements in patients with poorly differentiated tumors when the LHRH analogue was started during the last week of irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current studies of combined radiotherapy-hormone therapy in localized and locally advanced prostatic cancers]. Bolla, M., Artignan, X., Chirpaz, E., et al.[2019]

Goserelin, a GnRH agonist, is now approved in France as an adjuvant treatment alongside external radiotherapy for locally advanced prostate cancer, based on two well-conducted trials.

While the combination of radiotherapy and goserelin improves symptom-free survival, it is associated with significant side effects, including endocrine disorders in 19% of patients, increased urinary incontinence in 13%, and common occurrences of impotence and reduced libido.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Goserelin and locally advanced prostate cancer: new indication. Pros and cons. [2013]

GnRH analogues are established as safe and effective treatments for hormone-dependent advanced prostate cancer, but their unique mechanism of action complicates the entry of generic versions into the market.

Regulatory requirements for GnRH analogues are stringent due to their comparison with surgical castration, which has a 100% success rate, and they face competition from antagonistic treatments that do not cause flare-up effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacology and regulatory consequences of GnRH analogues in prostate cancer. Eckstein, N., Haas, B.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8105236/

Real-World Safety and Efficacy Outcomes with Abiraterone ... Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

2. urotoday.com urotoday.com/recent-abstracts/urologic-oncology/prostate-cancer/164459-overall-survival-in-patients-with-metastatic-castration-sensitive-prostate-cancer-treated-with-apalutamide-versus-abiraterone-acetate-a-head-to-head-analysis-of-real-world-patients-in-the-usa.html

a head-to-head analysis of real-world patients in the USA. The purpose of this study was to compare 24-month overall survival among ARPI-naive patients with metastatic castration-sensitive prostate ...

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Real-world overall survival with abiraterone acetate versus ... Comparison of real-life data of abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer. Sci Rep. 2021;11:14131.

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The Safety of Abiraterone Acetate in Patients with Metastatic ... Nearly all participants experienced at least one adverse event (98.4% abiraterone, 97.3% standard of care [SOC]).

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The Safety of Abiraterone Acetate in Patients with ... We observed a higher incidence of overall adverse events with the use of abiraterone acetate (98.4%) compared to (97.3%), though given the distribution of ...

8. e-juo.org e-juo.org/journal/view.php?number=594

Assessing Patient Risk, Benefit, and Outcomes in Drug ... Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint. Our ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33826036/

Real-World Safety and Efficacy Outcomes with Abiraterone ... Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.