Enzalutamide + M9241 for Recurrent Prostate Cancer

Overseen By Ravi A Madan, M.D.

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Enzalutamide

Must not be taking: CYP2C8, CYP3A4 inhibitors

Disqualifiers: Soft tissue disease, Bone lesions, Seizures, 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: 13

Duration: 12 weeks

65 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Prostate cancer may return after treatment in 30,000 to 50,000 people each year. There is no clear best way to treat these people. Better treatments are needed. Objective: To test a study drug (enzalutamide), both alone and combined with a second drug (PDS01ADC), in people with prostate cancer that returned after treatment. Eligibility: People aged 18 years and older with prostate cancer that returned after treatment. Design: Participants will be screened. They will have a physical exam, with blood tests. All their urine will be collected for 24 hours. They will have imaging scans of their chest, abdomen, pelvis, and bones. Their ability to perform everyday activities will be assessed. They may opt to give a stool sample. Participants will be treated in 4-week cycles. Enzalutamide is a pill taken by mouth once a day, every day. All participants will be given a supply of this drug to take at home. PDS01ADC is injected under the skin once a month, on the first day of each cycle. Half of the participants will receive both drugs. All participants will visit the clinic once a month. Each visit should last no more than 8 hours. Blood and urine tests will be repeated. All participants will receive the study treatment for 3 cycles. Some participants may need 3 more cycles of treatment with enzalutamide only. This re-treatment can be done only once. Participants will have a follow-up visit 1 month after they finish treatment. After that, they will have visits every 6 weeks for up to 5 years. Imaging scans and blood tests will be repeated. ...

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on medications that strongly affect certain liver enzymes (CYP2C8 or CYP3A4).

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

Research shows that Enzalutamide is effective in treating metastatic castration-resistant prostate cancer, improving overall survival and delaying disease progression compared to a placebo. It has been shown to significantly prolong life and improve quality of life in patients with advanced prostate cancer. ^{1 2 3 4 5}

Is the combination of Enzalutamide and M9241 safe for humans?

Enzalutamide, also known as Xtandi, is generally considered safe for treating prostate cancer, but it can cause side effects like skin reactions and cognitive changes. There is no specific safety data available for the combination with M9241 (NHS-IL12) in the provided research. ^{2 6 7 8 9}

What makes the drug Enzalutamide + M9241 unique for recurrent prostate cancer?

Enzalutamide is a second-generation androgen receptor inhibitor that has shown to improve survival in metastatic castration-resistant prostate cancer, while M9241 (NHS-IL12) is an investigational immunotherapy that may enhance the immune system's ability to fight cancer. This combination could offer a novel approach by targeting cancer through both hormonal and immune pathways, which is different from standard treatments like chemotherapy or radiation. ^{2 3 4 5 10}

Research Team

Ravi A Madan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Men aged 18+ with recurrent prostate cancer after primary treatment, a rising PSA level, and PSMA PET/CT scan evidence of cancer. They must have adequate organ function, agree to contraception use post-treatment for 3 months, and be able to swallow pills. Excluded are those with certain other medical conditions or allergies related to the study drugs.

Inclusion Criteria

Creatinine < 1.5 X institution ULN

Prostate-specific antigen (PSA) doubling time within less than 12 months.

Testosterone >100 ng/dL.

Exclusion Criteria

Evidence of bone lesions on Tc99 bone scan.

I am on long-term steroids or other drugs that weaken my immune system.

My scans show cancer in soft tissues, meeting specific size criteria.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive enzalutamide or enzalutamide plus M9241 in 4-week cycles for 3 cycles

12 weeks

3 visits (in-person, monthly)

Re-treatment

Participants who experience PSA recovery to baseline may receive a second course of enzalutamide treatment for 3 additional cycles

12 weeks

3 visits (in-person, monthly)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with visits every 6 weeks for up to 5 years

5 years

Visits every 6 weeks

Treatment Details

Interventions

• Enzalutamide
• M9241

Trial Overview The trial is testing enzalutamide (a daily pill) alone and combined with M9241 (a monthly injection), in men whose prostate cancer has returned. Participants will undergo cycles of treatment followed by regular clinic visits for monitoring up to five years.

Participant Groups

Group I: Arm 2 Experimental Treatment 2 Interventions

Enzalutamide+PDS01ADC

Group II: Arm 1 Experimental Treatment 1 Intervention

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 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 (Enz) was evaluated in a retrospective study of 47 men with heavily pretreated metastasized castration-resistant prostate cancer (mCRPC), showing a 23% response rate with significant PSA declines, indicating its potential efficacy even in later treatment lines.

The treatment was generally well tolerated, with common side effects like fatigue and nausea, and resulted in a median overall survival of 40.1 weeks and a median progression-free survival of 12.1 weeks, suggesting it can be a viable option for patients who have exhausted other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide as a Fourth- or Fifth-Line Treatment Option for Metastatic Castration-Resistant Prostate Cancer. Badrising, SK., van der Noort, V., Hamberg, P., et al.[2021]

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]

In a phase III trial involving patients with metastatic, castration-resistant prostate cancer (mCRPC) who had progressed after docetaxel treatment, enzalutamide significantly improved overall survival, with a median survival of 18.4 months compared to 13.6 months for placebo, indicating a 37% reduction in mortality risk.

Enzalutamide was generally well tolerated, with most side effects being mild to moderate, although there is a small, dose-dependent risk of seizures; it also improved quality of life and pain management for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer. Sanford, M.[2021]

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 (XTANDI) was approved by the FDA for treating metastatic castration-resistant prostate cancer based on a study of 1,199 patients, showing a significant improvement in overall survival (18.4 months for enzalutamide vs. 13.6 months for placebo).

The treatment was well-tolerated, with common side effects including fatigue and back pain, and a low incidence of seizures (0.9% in the enzalutamide group), indicating a favorable benefit-risk profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel: U.S. Food and Drug Administration drug approval summary. Ning, YM., Pierce, W., Maher, VE., et al.[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]

Enzalutamide significantly improves overall survival in men with metastatic, castration-resistant prostate cancer (mCRPC), showing a 37% reduced risk of death compared to placebo, with median survival times of 18.4 months versus 13.6 months.

The results from the phase III AFFIRM trial support the continued targeting of the androgen receptor as an effective treatment strategy for prostate cancer, even after patients have developed resistance to castration therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide (formerly MDV3100) as a new therapeutic option for men with metastatic castration-resistant prostate cancer. Aragon-Ching, JB.[2021]

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]

References

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

Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. [2021]

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

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

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

Enzalutamide as a Fourth- or Fifth-Line Treatment Option for Metastatic Castration-Resistant Prostate Cancer. [2021]

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

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

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

Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer. [2021]

6. Poland pubmed.ncbi.nlm.nih.gov

Enzalutamide induced acute generalized exanthematous pustulosis. [2020]

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

Enzalutamide for treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel: U.S. Food and Drug Administration drug approval summary. [2021]

8. Switzerland 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. [2023]

9. China pubmed.ncbi.nlm.nih.gov

Enzalutamide (formerly MDV3100) as a new therapeutic option for men with metastatic castration-resistant prostate cancer. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. [2021]