Androgen Deprivation Therapy + Enzalutamide for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Androgen deprivation, Enzalutamide

Must not be taking: CYP3A4 inhibitors, PgP inhibitors

Disqualifiers: Metastatic disease, Cardiac disease, Seizure history, 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: 4

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether a drug combination given before surgery can improve outcomes for men with localized prostate cancer. Researchers aim to determine if androgen deprivation therapy, including enzalutamide, can enhance surgery success rates and identify genetic traits linked to better outcomes. The trial also tests a new imaging method for more effective prostate cancer detection. Men who haven't received prior treatment for their prostate cancer and are candidates for prostate removal surgery may qualify. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in prostate cancer treatment.

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

The trial protocol does not specify if you need to stop all current medications, but you cannot take certain medications like strong inhibitors of CYP3A4 or P-glycoprotein, and medications for urinary symptoms like 5-alpha reductase inhibitors while on enzalutamide. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that combining enzalutamide with androgen deprivation therapy, including drugs like goserelin, is generally well-tolerated by patients. Past studies have demonstrated that this combination helps patients with advanced prostate cancer live longer. Although these studies focused on cancer that has spread, the safety results are encouraging.

Common side effects include fatigue, hot flashes, and high blood pressure. More serious side effects, such as heart problems and seizures, are less common but have been observed. Enzalutamide is already FDA-approved for other types of prostate cancer, indicating reasonable safety.

A study on intense testosterone-lowering therapy, which includes treatments like enzalutamide, found that most patients completed the treatment without stopping due to side effects. This suggests the treatment is generally manageable for patients.

Overall, the treatment combination appears safe, with some manageable side effects. Participants should discuss potential risks with healthcare providers to make informed decisions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining enzalutamide with goserelin for prostate cancer treatment because this approach could enhance the effectiveness of existing therapies. Enzalutamide is an androgen receptor inhibitor which blocks signals that help cancer cells grow, offering a different mechanism of action compared to traditional hormone therapies. When paired with goserelin, a medication that suppresses testosterone production, this combo targets prostate cancer from multiple angles, potentially leading to improved outcomes. This dual approach could be more effective at controlling cancer progression than current treatments that often rely on either hormone therapy or androgen receptor inhibition alone.

What evidence suggests that this treatment might be an effective treatment for prostate cancer?

Research has shown that enzalutamide and goserelin, administered together in this trial, effectively treat prostate cancer. Studies have found that adding enzalutamide to hormone treatments extends patients' lives, particularly for those with metastatic prostate cancer. In some cases, enzalutamide reduced the risk of death by nearly 30% compared to other treatments. Even for high-risk prostate cancer, this combination can improve survival without cancer spreading. These drugs block hormones that promote cancer growth, which might also be beneficial in earlier stages. ^{1 3 6 7 8}

Who Is on the Research Team?

Fatima Karzai, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Men 18+ with non-metastatic prostate cancer, eligible for surgery. Must have detectable lesions on MRI, agree to travel for follow-ups and undergo biopsy. No prior definitive therapy; intermediate/high-risk features required. Adequate contraception is necessary during and post-treatment.

Inclusion Criteria

My condition is considered to be of intermediate risk.

My prostate cancer is at an intermediate or high risk stage and has not been treated yet.

- Total bilirubin within normal institutional limits

Exclusion Criteria

You cannot undergo an MRI (a special type of medical scan) due to a medical condition or reason.

- Prothrombin Time (PT)/Partial Thromboplastin Time (PTT) greater than or equal to 1.5 times the upper limit of normal

- Patients weighing more than weight limit for the scanner tables

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive androgen deprivation therapy and enzalutamide for 6 months

6 months

Monthly visits (in-person)

Surgery

Participants undergo prostate removal surgery following treatment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• Goserelin
• Prostate Removal Surgery

Trial Overview

The trial tests if advanced imaging (mpMRI) can better detect prostate cancer pre- and post-treatment with a drug combo (androgen deprivation therapy + enzalutamide) before surgery, aiming to improve cure rates and identify genetic markers of good outcomes.

How Is the Trial Designed?

Group I: 1/Arm 1- Enzalutamide and Goserelin Experimental Treatment 3 Interventions

Patients will have an multi-parametric magnetic resonance imaging (mpMRI) guided biopsy, then receive enzalutamide and goserelin subcutaneous (SC) treatment for 6 months followed by a second mpMRI examination.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 67 men with hormone-naive prostate cancer, 92.5% experienced an 80% or greater decline in prostate-specific antigen (PSA) levels after 25 weeks of treatment with enzalutamide, indicating strong efficacy in disease suppression.

Enzalutamide was generally well tolerated, with most side effects being mild to moderate, although some patients experienced grade 3 adverse events like pneumonia and hypertension, which were not deemed treatment-related.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Commentary on: "Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study." Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T, Perabo F, Phung D, Hirmand M, Smith MR. Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium. Electronic address: [e-mail]. Aarhus University Hospital, Aarhus, Denmark. Herlev Hospital, Herlev, Denmark. AZ Groeninge Kortrijk, Kortrijk, Belgium. UZ Leuven, Leuven, Belgium. Klinik und Poliklinik für Urologie, RWTH University Aachen, Aachen, Germany. Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. UZ Brussel, Brussels, Belgium. Univerzita Karlova v Praze, Prague, Czech Republic. Astellas Pharma Global Development, Leiden, Netherlands. Astellas Pharma Global Development, Northbrook, IL, USA. Medivation Inc, San Francisco, CA, USA. Massachusetts General Hospital Cancer Center, Boston, MA, USA: Lancet Oncol. 2014 May;15(6):592-600; doi: 10.1016/S1470-2045(14)70129-9. [Epub 2014 Apr 14]. Trump, D.[2018]

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 significantly improves overall survival and radiographic progression-free survival in men with metastatic, castration-resistant prostate cancer (mCRPC), as shown in two major randomized trials (AFFIRM and PREVAIL) involving patients who had previously undergone chemotherapy and those who were chemotherapy naive.

While enzalutamide is generally safe and effective, it can cause side effects like fatigue and has specific safety concerns, such as an increased risk of seizures and falls, particularly in older patients (≥ 75 years).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. Graff, JN., Gordon, MJ., Beer, TM.[2021]

In a study involving 249 men with metastatic castrate-resistant prostate cancer, patient preference between darolutamide and enzalutamide was balanced, with no significant preference for either treatment (p = 0.92).

Darolutamide was associated with less fatigue and a moderate improvement in episodic memory compared to enzalutamide, suggesting it may offer a better quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. Colomba, E., Jonas, SF., Eymard, JC., et al.[2023]

ARAT agents like abiraterone acetate and enzalutamide improve survival rates in advanced prostate cancer but are associated with significant endocrine and metabolic side effects, such as hypertension and insulin resistance.

Darolutamide appears to have a safer side effect profile compared to other ARAT agents, suggesting that treatment for advanced prostate cancer should be personalized based on individual patient safety and risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine consequences of treatment with the new androgen receptor axis-targeted agents for advanced prostate cancer. Pyrgidis, N., Vakalopoulos, I., Sountoulides, P.[2021]

In a phase 3 trial involving 1401 men with nonmetastatic, castration-resistant prostate cancer, enzalutamide significantly improved median overall survival to 67.0 months compared to 56.3 months for placebo, indicating a 27% lower risk of death.

The safety profile of enzalutamide was consistent with previous studies, with a similar rate of serious adverse events compared to placebo, primarily involving fatigue and musculoskeletal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. Sternberg, CN., Fizazi, K., Saad, F., et al.[2021]

Enzalutamide significantly improved radiographic progression-free survival (rPFS) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer across various disease subgroups, including nonvisceral and visceral disease, as well as low- and high-volume bone disease.

The treatment was well tolerated, showing clinically significant benefits in overall survival (OS) for most subgroups, although the results were less definitive for patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer. Evans, CP., Higano, CS., Keane, T., et al.[2022]

In men with metastatic hormone-sensitive prostate cancer, enzalutamide, when combined with androgen-deprivation therapy, significantly prolonged radiographic progression-free survival compared to a placebo.

This finding highlights the efficacy of enzalutamide as an androgen-receptor inhibitor in improving outcomes for patients undergoing treatment for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eyeing Enzalutamide for Hormone-Sensitive Prostate Cancer. [2020]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

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 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]

In the SPARTAN study, apalutamide combined with androgen deprivation therapy (ADT) led to rapid and significant reductions in prostate-specific antigen (PSA) levels in most patients, with 90% achieving at least a 50% reduction by 6 months, compared to only 1.5% in the placebo group.

Deep PSA responses (≥90% reduction or PSA ≤0.2 ng/ml) at 6 months were strongly linked to improved outcomes, including metastasis-free survival and overall survival, indicating that early PSA monitoring can be a valuable prognostic tool for patients with high-risk nonmetastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN. Saad, F., Small, EJ., Feng, FY., et al.[2022]

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