Enzalutamide + Leuprolide for Prostate Cancer

Not currently recruiting at 302 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of enzalutamide and leuprolide for prostate cancer that has returned after surgery or radiation. Researchers aim to determine if this combination can manage the cancer more effectively than each drug alone. Participants take enzalutamide pills daily and receive leuprolide injections every 12 weeks. Men who had prostate cancer treated with surgery or radiation and now have rising PSA levels (a protein marker in the blood) might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that enzalutamide, used alone or with leuprolide, is generally safe for treating prostate cancer. Studies indicate that enzalutamide is usually well-tolerated, though some patients might experience side effects such as tiredness, hot flashes, and high blood pressure, which are typically manageable.

When combined with leuprolide, enzalutamide has improved survival rates without causing additional safety issues. The side effects are mostly similar to those seen with enzalutamide alone. The FDA has approved this combination for treating high-risk prostate cancer, supporting its safety for this condition.

Overall, while side effects can occur, research suggests that both treatments are relatively safe for prostate cancer patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they offer a fresh approach to managing the condition. Unlike traditional therapies that often involve surgery or radiation, enzalutamide targets androgen receptors, which are crucial in prostate cancer growth, effectively slowing down tumor development. When combined with leuprolide, which lowers testosterone levels, the treatment aims to more effectively inhibit cancer progression. This dual-action strategy could provide a more comprehensive treatment option, potentially improving outcomes for patients compared to current standard therapies.

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

In this trial, participants will receive different treatment options. Research has shown that combining enzalutamide and leuprolide, one of the treatment arms in this trial, greatly improves survival in men with high-risk prostate cancer that hasn't spread. Specifically, studies found that 87.3% of patients on this combination remained free from cancer spread after five years. Another arm in this trial involves enzalutamide monotherapy, which also performs well, significantly slowing cancer progression and reducing the risk of death by 33% compared to other treatments. Both options offer better results than standard therapies, providing hope for those with prostate cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

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.

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

Citations

1. 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) ...

2. 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 ...

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. xtandihcp.com xtandihcp.com/cspc/safety

Safety Profile in CSPC Data are n (%) shown for grade 3 adverse reactions occurring in >2% of participants and other relevant events associated with XTANDI.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34114527/

A drug safety evaluation of enzalutamide to treat advanced ... This literature review presents safety data from pivotal trials and real-world data studies of enzalutamide in patients with advanced PC.

8. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/xtandi

Xtandi | European Medicines Agency (EMA) Patients treated with Xtandi lived for an average of 37 months without their disease becoming metastatic compared with 15 months on placebo.

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/203415lbl.pdf

XTANDI (enzalutamide) capsules Label - accessdata.fda.gov The efficacy and safety of XTANDI in patients with metastatic castration-resistant prostate cancer who had received prior docetaxel-based therapy were ...

10. xtandihcp.com xtandihcp.com/crpc/safety

Safety CRPC | HCP Site | XTANDI® (enzalutamide) Learn about the efficacy and safety of XTANDI® (enzalutamide) in the results of the AFFIRM Trial for post-docetaxel mCRPC patients. See Risk Info.