Enzalutamide + M9241 for Recurrent Prostate Cancer
Recruiting in Palo Alto (17 mi)
Overseen byRavi A Madan, M.D.
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
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.
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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.
12345Is 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.
26789What 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.
234510Eligibility 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.
+18 more
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.
+5 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Arm 2Experimental Treatment2 Interventions
Enzalutamide+PDS01ADC
Group II: Arm 1Experimental Treatment1 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. [2021]Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic, castration-resistant prostate cancer and rapidly increasing prostate-specific antigen (PSA) levels while taking androgen-deprivation therapy. Results from the final analysis of overall survival have not yet been reported.
Enzalutamide for patients with metastatic castration-resistant prostate cancer. [2020]To review and evaluate current literature on the US Food and Drug Administration (FDA)-approved drug enzalutamide (XTANDI(®)) in metastatic castration-resistant prostate cancer.
Enzalutamide as a Fourth- or Fifth-Line Treatment Option for Metastatic Castration-Resistant Prostate Cancer. [2021]To evaluate the efficacy of enzalutamide (Enz) as fourth- or fifth-line treatment in men with metastasized castration-resistant prostate cancer (mCRPC), by analyzing a retrospective cohort of heavily pretreated patients.
The safety and efficacy of enzalutamide in the treatment of advanced prostate cancer. [2021]Enzalutamide - a non-steroidal second-generation antiandrogen - represents an active treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) in both chemotherapy-naïve and docetaxel-pretreated settings, based on the demonstration of improved overall survival over placebo in two large phase III trials.
Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer. [2021]Enzalutamide (MDV3100, XTANDI(®)) is an androgen receptor inhibitor that is indicated for the treatment of metastatic, castration-resistant, prostate cancer (mCRPC) that has progressed despite treatment with docetaxel. This article reviews the pharmacology, efficacy and tolerability of enzalutamide relevant to this indication. In a randomized, double-blind, placebo-controlled, multinational, phase III trial in patients with mCRPC progressing after docetaxel therapy, enzalutamide significantly prolonged overall survival (OS), delayed prostate specific antigen progression and prolonged radiographic progression-free survival and time to the first skeletal event. The median OS was 18.4 months in the enzalutamide group and 13.6 months in the placebo group, which represents a 37 % reduction in the mortality risk in the enzalutamide group. Enzalutamide was also associated with significant benefits in health-related quality of life and in pain palliation. Enzalutamide was generally as well tolerated as placebo during the trial, with most adverse events at a mild or moderate level of severity. Enzalutamide carries a small increased risk of seizures that appears to be dose-dependent. Enzalutamide is an efficacious and well tolerated treatment for this severe, rapidly progressive disease.
Enzalutamide induced acute generalized exanthematous pustulosis. [2020]Label="INTRODUCTION" NlmCategory="BACKGROUND"> Enzalutamide (Xtandi®) is a new potent inhibitor of the signaling pathway for the androgen receptor with a half-life of 5.8 days. It has been on the market for the treatment of metastatic castration-resistant prostate cancer since November 2013.
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]This article summarizes the regulatory evaluation that led to the full approval of enzalutamide (XTANDI, Medivation Inc.) by the U.S. Food and Drug Administration (FDA) on August 31, 2012, for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel. This approval was based on the results of a randomized, placebo-controlled trial which randomly allocated 1,199 patients with mCRPC who had received prior docetaxel to receive either enzalutamide, 160 mg orally once daily (n = 800), or placebo (n = 399). All patients were required to continue androgen deprivation therapy. The primary endpoint was overall survival. At the prespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for the enzalutamide arm compared with the placebo arm [HR = 0.63; 95% confidence interval: 0.53-0.75; P
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]Darolutamide and enzalutamide are second-generation androgen receptor inhibitors with activity in men with castrate-resistant prostate cancer (CRPC) and different toxicity profiles.
Enzalutamide (formerly MDV3100) as a new therapeutic option for men with metastatic castration-resistant prostate cancer. [2021]Enzalutamide marks the latest addition to the drugs currently approved by the US Food and Drug Administration for metastatic, castration-resistant prostate cancer (mCRPC). AFFIRMwas a phase III international randomized trial that evaluated the clinical utility of enzalutamide versus placebo in men with mCRPC who have failed prior docetaxel-containing chemotherapy. Enzalutamide showed a remarkable 37% decreased risk of death with a median overall survival of 18.4 months versus 13.6 months for those who received placebo. These findings confirm the validity of further targeting the androgen receptor as a valid therapeutic approach in prostate cancer despite emergence of castration resistance.
Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. [2021]Enzalutamide (MDV3100) is a second-generation androgen receptor antagonist that improves survival in metastatic, castration-resistant prostate cancer (mCRPC). Alternatives include chemotherapy, radiation, immunotherapy and abiraterone.