Relugolix + Enzalutamide with Radiation Therapy for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Northwestern University

Disqualifiers: Metastatic disease, Invasive malignancy, Inflammatory bowel disease, 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: 3

Duration: 18 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for individuals with very high-risk prostate cancer. It combines two medications, relugolix and enzalutamide, with radiation therapy to determine if this mix is more effective than using each treatment alone. Relugolix, a hormone therapy, lowers testosterone levels to slow cancer growth, while enzalutamide (also known as Xtandi) blocks signals that promote cancer cell growth. This trial may suit those with prostate cancer classified as very high risk, particularly if they have multiple cancerous areas or aggressive tumor characteristics. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on 5-alpha reductase inhibitors, you will need to stop them before starting the trial treatment.

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

Research has shown that relugolix is generally well-tolerated by patients. Common side effects include hot flashes, tiredness, weakness, constipation, and muscle pain. Importantly, one study found no new safety issues when relugolix was used with radiotherapy, similar to the treatment in this trial.

For enzalutamide, studies have indicated it is often safe and can help some prostate cancer patients live longer. However, like many medications, it can have side effects. The most common are tiredness and high blood pressure.

Both treatments have been successfully used in patients with prostate cancer, providing some reassurance about their safety. However, discussing personal risks with healthcare providers remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of relugolix and enzalutamide for prostate cancer because it offers a novel approach by simultaneously targeting two different hormonal pathways. While traditional treatments often focus solely on androgen deprivation, relugolix is an oral medication that provides a more direct and potentially faster way to decrease testosterone levels compared to injectable options. Enzalutamide adds another layer by blocking androgen receptors, preventing cancer cells from using androgens to grow. This dual approach aims to enhance the effectiveness of radiation therapy, potentially leading to better outcomes for patients.

What evidence suggests that relugolix and enzalutamide with radiation therapy might be an effective treatment for prostate cancer?

Research has shown that relugolix, one of the treatments in this trial, effectively lowers testosterone levels, which is crucial because testosterone promotes prostate cancer growth. In studies, over 90% of men with advanced prostate cancer experienced reduced testosterone levels with relugolix. Enzalutamide, another treatment option in this trial, blocks signals that cancer cells need to grow. It has been proven to extend patients' lives and slow cancer spread. This trial combines relugolix and enzalutamide with radiation therapy, aiming to enhance treatment effectiveness for high-risk prostate cancer by attacking the cancer in multiple ways. ^{2 3 5 6 7}

Who Is on the Research Team?

Sean Sachdev

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for patients with very high risk prostate cancer. Participants should be suitable for hormone therapy and radiation, have no prior treatments for their condition, and must be able to undergo imaging tests like MRI or CT scans.

Inclusion Criteria

My testosterone level was above 50 ng/dL in the last 3 months.

I use effective birth control methods.

Patients must have the ability to understand and sign a written informed consent document

Exclusion Criteria

I have been cancer-free for at least 2 years from a previous cancer.

My cancer has spread to other parts of my body.

I cannot take pills by mouth due to digestive issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive relugolix and enzalutamide orally once daily for 18 months, with image-guided radiation therapy starting after 4 months

18 months

Monthly visits for medication and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including PET/MRI and CT scans, blood sample collection, and biopsy

30 months

Every 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• Radiation Therapy
• Relugolix

Trial Overview The OPTIMAL trial is testing the combination of two drugs, Relugolix and Enzalutamide, with radiation therapy. The goal is to see if this combo is more effective in treating very high risk prostate cancer than standard therapies.

How Is the Trial Designed?

Group I: Treatment (relugolix, enzalutamide, IGRT) Experimental Treatment 10 Interventions

Patients receive relugolix PO QD and enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 18 months in the absence of disease progression or unacceptable toxicity. After 4 months of treatment with relugolix and enzalutamide, patients begin IGRT per standard of care. Patients also undergo fluorine F 18 piflufolastat PET/MRI and CT on the trial, undergo collection of blood samples throughout the trial, and undergo biopsy during follow up.

Enzalutamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in European Union as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Canada as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Japan as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Relugolix (Orgovyx) is the first oral medication approved for treating advanced prostate cancer, functioning as a gonadotropin-releasing hormone receptor antagonist.

While effective, relugolix carries risks such as prolonging the QT interval and potential embryo-fetal toxicity, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Oral Hormone for Treating Prostate Cancer. Aschenbrenner, DS.[2023]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

Enzalutamide is an effective androgen receptor inhibitor that improves overall survival in patients with metastatic castration-resistant prostate cancer, showing a 4.8-month survival benefit in those previously treated with docetaxel, as demonstrated in the Phase III AFFIRM trial.

The FDA has expanded enzalutamide's approval to include first-line treatment for metastatic castration-resistant prostate cancer in patients who have not yet received chemotherapy, and it is associated with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. Ramadan, WH., Kabbara, WK., Al Basiouni Al Masri, HS.[2020]

Enzalutamide (XTANDI) is an FDA-approved treatment for castration-resistant prostate cancer (CRPC) that effectively targets androgen receptor signaling, which is crucial for cancer progression.

In a Phase III clinical trial involving men with CRPC after chemotherapy, enzalutamide was well tolerated and significantly improved overall survival by 4.8 months, as indicated by reduced serum prostate-specific antigen (PSA) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. Dhingra, R., Sharma, T., Singh, S., et al.[2021]

In the phase III HERO trial, relugolix demonstrated a sustained castration rate of over 90% in men with advanced prostate cancer over 48 weeks, which was non-inferior to the traditional treatment with leuprolide, and showed potential superiority in exploratory analyses.

Relugolix is generally well tolerated and may have a lower risk of major adverse cardiac events compared to leuprolide, making it a promising oral treatment option for rapid testosterone suppression without the initial surge associated with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix: A Review in Advanced Prostate Cancer. Shirley, M.[2023]

In a phase 2 trial involving 11 patients with high-risk localized prostate cancer, the combination of enzalutamide with standard androgen deprivation therapy and radiation therapy was found to be well-tolerated, with only one patient experiencing a severe adverse event (seizure).

All patients achieved a complete response in prostate-specific antigen (PSA) levels, with a median time to PSA complete response of 4.2 months, and at 24 months, none of the patients had a biochemical recurrence, indicating strong efficacy of the treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of Enzalutamide to Leuprolide and Definitive Radiation Therapy Is Tolerable and Effective in High-Risk Localized or Regional Nonmetastatic Prostate Cancer: Results From a Phase 2 Trial. Shee, K., de la Calle, CM., Chang, AJ., et al.[2022]

In a phase 2 study involving 103 intermediate-risk prostate cancer patients, relugolix achieved effective castration rates of 95% and 82% for testosterone levels below 1.73 nmol/l and 0.7 nmol/l, respectively, within just 4 days of treatment.

Relugolix demonstrated a favorable safety profile similar to that of degarelix, with common side effects like hot flushes, and showed potential as an effective oral alternative to injectable androgen deprivation therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Oral Gonadotropin-releasing Hormone Receptor Antagonist Relugolix as Neoadjuvant/Adjuvant Androgen Deprivation Therapy to External Beam Radiotherapy in Patients with Localised Intermediate-risk Prostate Cancer: A Randomised, Open-label, Parallel-group Phase 2 Trial. Dearnaley, DP., Saltzstein, DR., Sylvester, JE., et al.[2023]

In a study of 86 men with recurrent prostate cancer, combining enzalutamide (ENZA) with salvage radiation therapy (SRT) significantly improved freedom from prostate-specific antigen (PSA) progression, with a 2-year FFPP of 84% for ENZA compared to 66% for placebo.

The treatment was found to be safe, with common side effects including fatigue and urinary frequency, but the long-term effects on distant metastasis or overall survival are still unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Randomized Study of Salvage Radiation Therapy Plus Enzalutamide or Placebo for High-Risk Prostate-Specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy: The SALV-ENZA Trial. Tran, PT., Lowe, K., Tsai, HL., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303974

Improved Outcomes with Enzalutamide in Biochemically ... After a median follow-up of 60.7 months, enzalutamide plus leuprolide and enzalutamide monotherapy significantly improved metastasis-free ...

2. pfizer.com pfizer.com/news/press-release/press-release-detail/astellas-and-pfizers-xtanditm-enzalutamide-shows-long-term

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) ...

3. xtandihcp.com xtandihcp.com/cspc/efficacy

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 ...

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

5. xtandi.com xtandi.com/clinical-trials

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 ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa2510310

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- ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2833622

Enzalutamide and Prostate-Specific Antigen Levels in ... In this study, enzalutamide plus ADT was associated with improved outcomes in men with mHSPC regardless of pretreatment PSA level.