Enzalutamide + ADT + Radiation for Prostate Cancer

(ENZARAD Trial)

Not currently recruiting at 70 trial locations
Age: 18+
Sex: Male
Trial Phase: Phase 3
Sponsor: University of Sydney
Must be taking: LHRHA
Stay on Your Current MedsYou can continue your current medications while participating
No Placebo GroupAll 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 DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of enzalutamide (Xtandi) combined with hormone therapy and radiation for men with prostate cancer at high risk of recurrence. The researchers aim to determine if adding enzalutamide to standard hormone treatment can better prevent cancer from returning. Men with localized prostate cancer, who are at high risk for recurrence and suitable for radiation therapy, might be good candidates. The trial will compare two groups: one taking enzalutamide and another using a conventional anti-androgen pill. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that enzalutamide is generally well-tolerated. Studies have found that enzalutamide can significantly reduce the risk of death compared to other treatments. In one study, combining enzalutamide with another drug improved survival rates by 40% compared to using the other drug alone, indicating that enzalutamide is both effective and relatively safe.

Another study with over 2,000 patients found that enzalutamide lowered the risk of death by 33%. While effective, some people may experience side effects like tiredness, hot flashes, and high blood pressure, though serious side effects are rare.

Overall, these studies show that enzalutamide is safe for many patients, with benefits often outweighing risks. Understanding these findings can help prospective trial participants make informed decisions.12345

Why are researchers excited about this trial's treatments?

Most treatments for prostate cancer involve hormone therapies that suppress testosterone, often combined with radiation. But Enzalutamide offers a novel twist by directly blocking the androgen receptor, which can make cancer cells more vulnerable to treatment. Researchers are particularly excited about combining Enzalutamide with ADT and radiation because it might enhance the treatment's effectiveness against prostate cancer. By targeting the cancer in multiple ways—hormonal suppression and receptor blocking—this approach could improve outcomes compared to conventional therapies alone.

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

Research has shown that enzalutamide, one of the treatments in this trial, effectively treats prostate cancer. One study found that patients taking enzalutamide had a 50% chance of surviving for 96 months, compared to 40% for those using a standard non-steroidal anti-androgen (NSAA), another treatment arm in this trial. Another study reported that after two years, 80% of patients on enzalutamide were still alive, compared to 63% of those on other treatments. Additionally, enzalutamide lowered the risk of cancer progression by 60% and reduced the risk of death by 33% in some patient groups. These results suggest that enzalutamide can be a strong option for prostate cancer treatment.13678

Who Is on the Research Team?

PN

Paul Nguyen

Principal Investigator

Dana Farber Cancer Institute and ANZUP

SW

Scott Williams

Principal Investigator

ANZUP and Peter MacCallum Cancer Centre

Are You a Good Fit for This Trial?

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.
See 6 more

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.
See 11 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: EnzalutamideExperimental Treatment3 Interventions
Group II: Conventional Non-steroidal Anti-androgen (NSAA)Active Control3 Interventions

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

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Approved in European Union as External Beam Radiotherapy for:
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Approved in United States as External Beam Radiotherapy for:
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Approved in Canada as External Beam Radiotherapy for:
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Approved in Japan as External Beam Radiotherapy for:
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Approved in China as External Beam Radiotherapy for:
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Approved in Switzerland as External Beam Radiotherapy for:

Find a Clinic Near You

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+

Published Research Related to This Trial

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.
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]
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.
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]
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.
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]

Citations

Astellas and Pfizer's XTANDI™ (enzalutamide) Shows ...OS at 96 months was 50% with XTANDI and 40% for NSAA; progression-free survival (PFS) also favored XTANDI over NSAA (HR: 0.49; 95% CI, 0.42-0.57) ...
A 13-Year-Old Drug's Persisting Power in Prostate CancerTwo-year OS rates were 80% vs 63%. The treatment also yielded a record 57.1% pathological pCR. ... Clinical Trial Achieves 60% Reduction in the Risk of Tumor ...
Improved Survival with Enzalutamide in Biochemically ...In this trial, enzalutamide plus leuprolide led to significantly longer overall survival than leuprolide alone among patients with castration- ...
Efficacy CSPC | HCP Site | XTANDI® (enzalutamide)XTANDI (single agent) significantly improved metastasis-free survival vs placebo + GnRH therapy* · Number of events: 63 (17.7%) with XTANDI (single agent) vs 92 ...
5.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/40660075/
The efficacy and safety of enzalutamide in metastatic ...Results: The data of 2275 patients were analyzed eventually. Enzalutamide reduced the risk of death by 33% compared to the control. Specifically ...
XTANDI® Plus Leuprolide Reduced Risk of Death by 40% ...The probability of survival at 8 years was an unprecedented 78.9% with XTANDI plus leuprolide versus 69.5% with leuprolide, in men with ...
Comparative effectiveness and safety of enzalutamide ...Enzalutamide use was associated with superior overall survival (hazard ratio 0.88, 95% confidence interval [CI] 0.82–0.96) compared with ...
Clinical Trial Results | XTANDI® (enzalutamide)Men taking XTANDI had a 61% lower chance of their cancer progressing compared with men not taking XTANDI during the study. Progression was seen in 89 men (15.5 ...
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