Enzalutamide + ADT + Radiation for Prostate Cancer

(ENZARAD Trial)

Recruiting at 69 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: University of Sydney

Must be taking: LHRHA

Must not be taking: Hormonal therapy

Disqualifiers: Metastatic disease, Seizure history, Cardiovascular, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

802 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the effectiveness of enzalutamide as part of adjuvant androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone analogue (LHRHA) in men having radiation therapy for localised prostate cancer at high risk of recurrence.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that you cannot use hormonal therapy or androgen deprivation therapy, except for specific cases. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Enzalutamide + ADT + Radiation for Prostate Cancer?

Research shows that combining external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. However, the benefits of adding brachytherapy to this combination are not clear. ^{1 2 3 4 5}

Is the combination of Enzalutamide, ADT, and Radiation Therapy safe for humans?

Research shows that external beam radiation therapy (EBRT) combined with androgen deprivation therapy (ADT) for prostate cancer can cause side effects like bowel, bladder, and sexual function issues. However, these treatments are generally considered safe for humans, with recovery of sexual and hormonal function possible after treatment. ^{1 6 7 8 9}

How does the treatment of Enzalutamide + ADT + Radiation for Prostate Cancer differ from other treatments?

This treatment combines enzalutamide, a potent drug that blocks male hormones, with androgen deprivation therapy (ADT) and external beam radiotherapy (EBRT), aiming to enhance tumor control and improve survival in high-risk prostate cancer. It is unique because enzalutamide is a next-generation drug that has shown effectiveness in advanced prostate cancer, and its combination with radiation and hormone therapy may offer a more comprehensive approach to managing the disease. ^{1 2 5 10 11}

Research Team

Paul Nguyen

Principal Investigator

Dana Farber Cancer Institute and ANZUP

Scott Williams

Principal Investigator

ANZUP and Peter MacCallum Cancer Centre

Eligibility Criteria

Men over 18 with high-risk, localized prostate cancer that hasn't spread beyond certain lymph nodes. They must have a specific Gleason score or PSA level and be in good health with proper organ function. Participants need to start treatment within a week of joining and can't have had certain other cancers or treatments.

Inclusion Criteria

I can start the study treatment within a week of being chosen.

My liver tests are within the normal range.

My prostate cancer is high risk with a specific Gleason score, PSA level, or lymph node involvement.

Exclusion Criteria

My scans show cancer has spread, but no bone cancer is evident without specific tests.

My prostate cancer has specific aggressive features.

My cancer has spread to lymph nodes above my pelvis or outside it, confirmed by tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enzalutamide as part of adjuvant androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone analogue (LHRHA) and radiation therapy

24 months

Regular visits for treatment administration and monitoring

Radiation

External beam radiation therapy started approximately 16 weeks after randomisation

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Brachytherapy
• Enzalutamide
• External Beam Radiotherapy
• LHRHA

Trial Overview The trial is testing if adding enzalutamide to standard hormone therapy (LHRHA) improves outcomes for men undergoing radiation therapy for prostate cancer. Patients are randomly assigned to receive either enzalutamide or a conventional nonsteroidal antiandrogen along with LHRHA and targeted radiotherapy.

Participant Groups

Group I: Enzalutamide Experimental Treatment 3 Interventions

Enzalutamide 160 mg daily, by mouth, for 24 months from randomisation. All participants are treated with a LHRHA for 24 months from randomisation and external beam radiation therapy started approximately 16 weeks after randomisation (+/- brachytherapy boost)

Group II: Conventional Non-steroidal Anti-androgen (NSAA) Active Control 3 Interventions

Conventional Non-steroidal Anti-androgen (NSAA), by mouth, for 6 months from randomisation. All participants are treated with a LHRHA for 24 months from randomisation and external beam radiation therapy started approximately 16 weeks after randomisation (+/- brachytherapy boost)

External Beam Radiotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as External Beam Radiotherapy for:

• Cancer treatment including but not limited to breast cancer, lung cancer, prostate cancer, head and neck cancer

Approved in United States as External Beam Radiotherapy for:

• Cancer treatment including but not limited to breast cancer, lung cancer, prostate cancer, head and neck cancer

Approved in Canada as External Beam Radiotherapy for:

• Cancer treatment including but not limited to breast cancer, lung cancer, prostate cancer, head and neck cancer

Approved in Japan as External Beam Radiotherapy for:

• Cancer treatment including but not limited to breast cancer, lung cancer, prostate cancer, head and neck cancer

Approved in China as External Beam Radiotherapy for:

• Cancer treatment including but not limited to breast cancer, lung cancer, prostate cancer, head and neck cancer

Approved in Switzerland as External Beam Radiotherapy for:

• Cancer treatment including but not limited to breast cancer, lung cancer, prostate cancer, head and neck cancer

Who Is Running the Clinical Trial?

University of Sydney

Lead Sponsor

Trials

208

Recruited

417,000+

Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Collaborator

Trials

21

Recruited

7,000+

National Health and Medical Research Council, Australia

Collaborator

Trials

167

Recruited

473,000+

Trans Tasman Radiation Oncology Group

Collaborator

Trials

50

Recruited

16,600+

TROG- Trans Tasman Radiation Oncology Group

Collaborator

Trials

1

Recruited

800+

European Organisation for Research and Treatment of Cancer - EORTC

Collaborator

Trials

417

Recruited

166,000+

Cancer Trials Ireland

Collaborator

Trials

85

Recruited

25,600+

Findings from Research

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]

In a study of 46,325 men with high-risk prostate cancer, androgen deprivation therapy (ADT) improved overall survival for those receiving external beam radiation therapy (EBRT) alone, but not for those receiving combined EBRT and brachytherapy.

The findings suggest that while ADT is beneficial with EBRT, it may not enhance survival in patients treated with both EBRT and brachytherapy, highlighting the need for further research to evaluate the risks and benefits of ADT in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of Apparent Survival Benefit With Use of Androgen Deprivation Therapy in Patients With High-risk Prostate Cancer Receiving Combined External Beam Radiation Therapy and Brachytherapy. Yang, DD., Muralidhar, V., Mahal, BA., et al.[2018]

In a study of 263 patients with locally advanced prostate cancer, combining androgen-deprivation therapy (ADT) with external beam radiation therapy (EBRT) significantly improved progression-free survival (PFS) rates at 8 years (48% vs 7%) compared to ADT alone, indicating a strong oncological benefit of the combination treatment.

The risk of death from prostate cancer was reduced by nearly half in the ADT+EBRT group, demonstrating that this combination not only prolongs survival without disease progression but also enhances disease-specific survival, despite similar overall survival rates between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term androgen deprivation, with or without radiotherapy, in locally advanced prostate cancer: updated results from a phase III randomised trial. Sargos, P., Mottet, N., Bellera, C., et al.[2020]

A study of 1,825 men with prostate cancer treated with external beam radiation therapy (EBRT) found that location of treatment significantly influenced the level of adverse effects, with one regional cancer service reporting a higher 'big bother' rate (11.1%) compared to the rest of Victoria (4.8%).

The study indicates that while the technique of EBRT did not show a significant impact on patient outcomes over time, the variation in patient-reported adverse effects highlights the importance of monitoring and evaluating treatment locations for better patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of patient-reported quality of life outcomes after external beam radiation treatment for prostate cancer in Victoria: A cohort study by the Victorian Prostate Cancer Registry. Patabendi Bandarage, VR., Billah, B., Millar, JL., 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 study of 48 men with intermediate or high-risk localized prostate cancer, the combination therapy of enzalutamide, dutasteride, and leuprolide resulted in a pathologic complete response (pCR) rate of 4.3% and minimal residual disease (MRD) in 13.0% of patients, indicating some effectiveness in reducing cancer prior to surgery.

In contrast, the enzalutamide-only group showed no patients achieving pCR or MRD, and had a higher median residual cancer burden, suggesting that the combination therapy may be more effective in managing prostate cancer by better targeting androgen receptor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Enzalutamide Prior to Prostatectomy. Montgomery, B., Tretiakova, MS., Joshua, AM., et al.[2021]

The SALV-ENZA trial is a phase II study involving adult males with recurrent prostate cancer after surgery, testing the effectiveness of combining salvage radiation therapy (SRT) with the anti-androgen enzalutamide to improve outcomes like freedom from PSA progression.

This study aims to determine if adding enzalutamide, known for its favorable side effect profile, enhances the efficacy of SRT compared to standard treatment alone, potentially leading to better clinical outcomes and paving the way for future phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA). Kapoor, R., Deek, MP., McIntyre, R., et al.[2021]

References

1. 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]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Estimating the Impact of Randomised Control Trial Results on Clinical Practice: Results from a Survey and Modelling Study of Androgen Deprivation Therapy plus Radiotherapy for Locally Advanced Prostate Cancer. [2022]

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

Lack of Apparent Survival Benefit With Use of Androgen Deprivation Therapy in Patients With High-risk Prostate Cancer Receiving Combined External Beam Radiation Therapy and Brachytherapy. [2018]

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

Long-term androgen deprivation, with or without radiotherapy, in locally advanced prostate cancer: updated results from a phase III randomised trial. [2020]

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

Salvage of locally recurrent prostate cancer after external beam radiation using reduced-dose brachytherapy with neoadjuvant plus adjuvant androgen deprivation. [2022]

6. Poland pubmed.ncbi.nlm.nih.gov

Localized prostate cancer treated with external beam radiation therapy: Long-term outcomes at a European comprehensive cancer centre. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Prospective evaluation of patient-reported quality of life outcomes after external beam radiation treatment for prostate cancer in Victoria: A cohort study by the Victorian Prostate Cancer Registry. [2018]

8. United States 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. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Trimodal therapy with high-dose-rate brachytherapy and hypofractionated external beam radiation combined with long-term androgen deprivation for unfavorable-risk prostate cancer. [2022]

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

Neoadjuvant Enzalutamide Prior to Prostatectomy. [2021]

11. England pubmed.ncbi.nlm.nih.gov

A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA). [2021]