Enzalutamide Implants for Prostate Cancer

Overseen By Pamela Munster, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Alessa Therapeutics Inc.

Must not be taking: 5 alpha reductase inhibitors

Disqualifiers: Prior radiotherapy, Hormonal therapy, Metastatic disease, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6-12 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Enolen, which uses implants to deliver the drug enzalutamide (also known as Xtandi) directly to the prostate. The goal is to determine if this treatment is safe and effective in reducing androgens, hormones that fuel prostate cancer, in men planning to have their prostate removed. The trial seeks men diagnosed with prostate cancer who are scheduled for surgery. Participants should have a prostate tumor clearly visible on an MRI scan. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

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 have ongoing hormonal therapy for prostate cancer or use 5 alpha reductase inhibitors within 3 months of starting the trial.

What prior data suggests that Enolen implants are safe for prostate cancer patients?

Research shows that enzalutamide, the active ingredient in the Enolen implants, is generally well-tolerated by patients with prostate cancer. The FDA has already approved enzalutamide in pill form for treating prostate cancer, confirming its safety profile.

In the pill form, some patients have reported side effects such as fatigue, hot flashes, and high blood pressure. However, the implant version of enzalutamide is still under study, so specific safety information remains limited. As this is an early-phase trial, the primary goal is to ensure the implants are safe. Early trials like this one focus on monitoring for any possible side effects to ensure safety.

Prospective participants will be closely monitored for any side effects. The trial aims to confirm that the implant's drug delivery method is safe for patients awaiting prostate surgery. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Enolen™ because it uses a novel delivery method: implants containing enzalutamide. Unlike traditional oral medications for prostate cancer, like hormone therapies or chemotherapy, Enolen™ provides a steady release of the active ingredient directly into the body, potentially reducing side effects and improving patient compliance. This targeted approach could lead to more consistent therapeutic levels and enhanced effectiveness, offering a promising new option for managing prostate cancer.

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

Research shows that enzalutamide, used in the Enolen implant under study in this trial, has promising results for treating prostate cancer. Studies have found that men taking enzalutamide had a 61% lower chance of their cancer worsening compared to those not taking it. In another study, survival rates improved with enzalutamide, with 50% of patients surviving at 96 months compared to 40% in the other group. The treatment also extended the time patients lived without their cancer spreading. These findings suggest that enzalutamide could effectively manage prostate cancer by blocking the hormones that help the cancer grow. ^{1 3 6 7 8}

Who Is on the Research Team?

Peter Pinto, MD

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Men over 21 with prostate cancer, a Gleason score of at least 3+4, and PSA levels ≥3 ng/mL. They must be fit for surgery, have no history of prostate infection in the last two years or hormonal therapy within three months. No metallic implants that affect MRI quality or conditions preventing surgery are allowed.

Inclusion Criteria

I am fully active or can carry out light work.

I am at least 21 years old.

PSA greater or equal to 3 ng/mL within 3 months of screening

Exclusion Criteria

My cancer has spread to other parts of my body.

Metallic hip implant or any other metallic implant or device that distorts the quality of prostatic MR images

I am currently on hormone therapy for prostate cancer or was on it less than 3 months ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants undergo multiparametric MRI of the prostate

1 week

1 visit (in-person)

Treatment

Placement of drug eluting Enolen implants and follow-up MRI

6-12 weeks

2 visits (in-person)

Surgery

Participants undergo standard of care radical prostatectomy

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery, including clinical labs and quality of life questionnaires

6-12 weeks

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide

Trial Overview The trial is testing Enolen implants to see if they safely deliver anti-androgen medication directly to the prostate before radical prostatectomy. Participants will undergo MRI post-treatment to assess the implant's effects.

How Is the Trial Designed?

Group I: Enolen (tm) Experimental Treatment 1 Intervention

Enolen (tm) implants containing enzalutamide

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?

Alessa Therapeutics Inc.

Lead Sponsor

Trials

3

Recruited

60+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Enzalutamide, a treatment for metastatic castration-resistant prostate cancer, was linked to a case of acute generalized exanthematous pustulosis (AGEP) in a 62-year-old male patient, indicating a potential skin-related side effect of this medication.

The patient's skin reaction occurred shortly after starting enzalutamide and resolved within four weeks, suggesting that the long half-life of enzalutamide (5.8 days) may contribute to the prolonged duration of symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide induced acute generalized exanthematous pustulosis. Alberto, C., Konstantinou, MP., Martinage, C., et al.[2020]

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 survival and delays skeletal-related events in patients with metastatic castration-resistant prostate cancer (mCRPC), as shown in the phase III AFFIRM study with consistent benefits across all subgroups.

In the phase III PREVAIL study, enzalutamide reduced the risk of radiographic progression and death in chemotherapy-naïve mCRPC patients, while also demonstrating a favorable safety profile with similar adverse event rates compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on enzalutamide in the treatment of prostate cancer. Merseburger, AS., Haas, GP., von Klot, CA.[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 PREVAIL trial, enzalutamide significantly improved both radiographic progression-free survival and overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (CRPC), demonstrating its efficacy as a treatment option.

Enzalutamide was well tolerated and delayed the need for chemotherapy and decline in health-related quality of life, making it a convenient choice for patients who are asymptomatic or mildly symptomatic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a review of its use in chemotherapy-naïve metastatic castration-resistant prostate cancer. Keating, GM.[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]

The ENZAMET phase III trial demonstrated that adding enzalutamide to standard treatment significantly prolongs survival in men with metastatic hormone-sensitive prostate cancer.

Enzalutamide is more effective than older nonsteroidal antiandrogen drugs, highlighting its potential as a superior treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide Bests Older NSAAs in mHSPC. [2021]

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]

Oral enzalutamide (Xtandi®) is an effective treatment for castration-resistant prostate cancer (CRPC), showing efficacy in both nonmetastatic and metastatic cases, as well as in patients who have or have not undergone chemotherapy.

Enzalutamide is generally well tolerated and is particularly beneficial for high-risk nonmetastatic CRPC patients, making it a key first-line treatment option for those with metastatic CRPC, regardless of their chemotherapy history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: A Review in Castration-Resistant Prostate Cancer. Scott, LJ.[2021]

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8149336/

Deep and ongoing response of castrate-resistant prostate ... This case report shows long-term effectiveness of a low dose enzalutamide (40 mg qd) in an 82-year-old patient with metastatic CRPC. No significant side effects ...

3. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06257693?cond=NCT06257693&rank=1

Enzalutamide Implants (Enolen) in Patients With Prostate ... Study Overview​​ This study is a single-center, open-label feasibility study. Up to 20 participants planning for radical prostatectomy will be recruited to ...

5. 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) ...

6. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=001837-C&&query=

NIH Clinical Center: Search the Studies This study is a single-center, open-label feasibility study. Up to 20 participants planning for radical prostatectomy will be recruited to assess the safety ...

7. trialx.com trialx.com/clinical-trials/listings/302052/enzalutamide-implants-enolen-in-patients-with-prostate-cancer/

Enzalutamide Implants (Enolen) in Patients With Prostate ... The study is to assess whether the Enolen is safe and delivers anti-androgen medication locally in patients that are planning for radical ...

8. app.trialscreen.org app.trialscreen.org/trials/phase-1-enzalutamide-implants-enolen-patients-prostate-cancer-trial-nct06257693

Enzalutamide Implants (Enolen) in Patients With Prostate ... A Phase 1 Study of Enzalutamide Implants in Prostate Cancer. Evaluating the Safety and Localized Delivery of Enzalutamide Implants in Prostate Cancer Patients ...