Enzalutamide + Leuprolide for Prostate Cancer

Recruiting at 269 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Must not be taking: Hormonal therapy, Chemotherapy

Disqualifiers: Metastatic disease, Recent surgery, others

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: Up to 98 months

1068 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess enzalutamide plus leuprolide in patients with high-risk nonmetastatic prostate cancer progressing after radical prostatectomy or radiotherapy or both. The randomized / blinded portion of the study is now completed following primary endpoint analyses. The study remains ongoing in open label format.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as 5-α reductase inhibitors (like finasteride or dutasteride), at least 4 weeks before joining. If you are on hormonal therapy, it must have been completed at least 9 months before joining the trial.

What data supports the effectiveness of the drug Enzalutamide + Leuprolide for prostate cancer?

Research shows that leuprolide, delivered through implants like Viadur, is effective in treating advanced prostate cancer by maintaining low testosterone levels, which helps control cancer growth. Enzalutamide, another component, is FDA-approved for treating metastatic castration-resistant prostate cancer, indicating its effectiveness in managing advanced stages of the disease. ^{1 2 3 4 5}

Is the combination of Enzalutamide and Leuprolide safe for humans?

Enzalutamide has been shown to have a generally favorable safety profile in clinical trials for prostate cancer, with common side effects including fatigue, diarrhea, back pain, and hot flashes. Some patients experienced high blood pressure and breast-related disorders, and a few had seizures. Leuprolide, used in prostate cancer treatment, is generally well-tolerated but can cause hot flashes, mood changes, and injection site reactions. ^{5 6 7 8 9}

How is the drug combination of Enzalutamide and Leuprolide unique for treating prostate cancer?

The combination of Enzalutamide and Leuprolide is unique because it combines a non-steroidal antiandrogen (Enzalutamide) with a hormone therapy (Leuprolide) that suppresses testosterone, potentially offering a more comprehensive approach to managing advanced prostate cancer compared to using either drug alone. ^{3 10 11 12 13}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

Men with high-risk, nonmetastatic prostate cancer that's progressing after surgery or radiation can join. They need a PSA doubling time of ≤9 months and certain PSA levels depending on prior treatments. Exclusions include recent use of specific drugs, brain metastasis, distant metastases, previous hormonal therapy (with some exceptions), chemotherapy for prostate cancer, major surgery within the last month, or another invasive cancer in the past 3 years.

Inclusion Criteria

Serum testosterone ≥ 150 ng/dL (5.2 nmol/L)

My PSA level is above 1 ng/mL after prostate surgery or 2 ng/mL above the lowest point after radiotherapy.

My prostate cancer was initially treated with surgery or radiation aimed at curing it.

Exclusion Criteria

I have not taken finasteride or dutasteride in the last 4 weeks.

I have received specific treatments for prostate cancer.

My cancer has spread to distant parts of my body, confirmed by scans.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enzalutamide plus leuprolide, enzalutamide monotherapy, or leuprolide plus placebo

Up to 98 months

Open-label extension

Participants continue to receive leuprolide alone in an open-label format

Ongoing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Enzalutamide
• Leuprolide

Trial Overview The study is testing enzalutamide combined with leuprolide against prostate cancer that hasn't spread elsewhere in the body. The trial was initially randomized and blinded but now continues as an open-label study where everyone receives the actual treatment without any placebo.

Participant Groups

Group I: Enzalutamide plus leuprolide Experimental Treatment 2 Interventions

Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with leuprolide administered as as a single intramuscular or subcutaneous injection once every 12 weeks

Group II: Enzalutamide monotherapy Experimental Treatment 1 Intervention

Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily

Group III: Leuprolide plus placebo Active Control 1 Intervention

Enzalutamide placebo (placebo) capsules (identical in appearance to enzalutamide) administered as 4 capsules by mouth once daily in combination with leuprolide administered as a single intramuscular or subcutaneous injection once every 12 weeks. The randomized blinded portion of the study has concluded following primary endpoint analyses. In the Open Label Period the placebo is no longer applicable in this study arm, and patients continue to receive leuprolide alone.

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?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Astellas Pharma Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Industry Sponsor

Trials

24

Recruited

10,200+

Findings from Research

The Viadur++ leuprolide delivery system effectively suppressed testosterone levels to the castrate range in 100% of patients over a 12-month period, demonstrating its efficacy in treating advanced prostate cancer.

The treatment was well tolerated, with no serious adverse events linked to the implant, indicating a favorable safety profile for patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of an implantable leuprolide delivery system in patients with advanced prostate cancer. Fowler, JE., Gottesman, JE., Reid, CF., et al.[2019]

In a study involving 1,906 patients with advanced prostate cancer, both 3-month and 6-month leuprorelin acetate depot formulations significantly reduced prostate-specific antigen (PSA) levels from an average of 12.0 ng/mL to 0.5 ng/mL after 12 months, indicating effective treatment.

The treatment was well-tolerated, with only 8.8% of patients experiencing adverse events, suggesting that leuprorelin acetate is a safe option for managing advanced prostate cancer in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer. Ohlmann, CH., Gross-Langenhoff, M.[2018]

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]

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, 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]

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]

In a study involving 1919 patients with metastatic prostate cancer, the addition of abiraterone acetate to standard androgen deprivation therapy significantly improved overall survival, with a median survival of 76.6 months compared to 45.7 months for standard care alone.

Combining both abiraterone and enzalutamide did not provide additional survival benefits over abiraterone alone, and it was associated with higher rates of severe side effects, suggesting that this combination should be avoided in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

Enzalutamide has been shown to significantly improve overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC), both in those who have not received chemotherapy and those who have been pretreated with docetaxel, based on results from large phase III trials.

The current treatment landscape for mCRPC has expanded beyond just docetaxel to include various therapies, but there is still a need for direct comparisons between these treatments to determine the best sequence for patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of enzalutamide in the treatment of advanced prostate cancer. Ciccarese, C., Nobili, E., Grilli, D., et al.[2021]

References

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

Safety and efficacy of an implantable leuprolide delivery system in patients with advanced prostate cancer. [2019]

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

Evaluation of an implant that delivers leuprolide for 1 year for the palliative treatment of prostate cancer. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer. [2018]

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

Luteinizing hormone-releasing hormone agonists in the treatment of men with prostate cancer: timing, alternatives, and the 1-year implant. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. [2020]

6. Australia pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

An update on enzalutamide in the treatment of prostate cancer. [2020]

8. Poland pubmed.ncbi.nlm.nih.gov

Enzalutamide induced acute generalized exanthematous pustulosis. [2020]

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

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]

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

Clinical effects of gonadotropin-releasing hormone analogue in metastatic carcinoma of prostate. [2019]

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

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. [2023]

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

Androgen suppression by a gonadotropin releasing hormone analogue in patients with metastatic carcinoma of the prostate. [2019]

13. England pubmed.ncbi.nlm.nih.gov

The safety and efficacy of enzalutamide in the treatment of advanced prostate cancer. [2021]