Androgen Receptor Antagonists for Prostate Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Beth Israel Deaconess Medical Center
Must be taking: AR antagonists
Must not be taking: Older AR antagonists
Disqualifiers: High disease burden, others
No Placebo Group
Approved in 6 Jurisdictions
Trial Summary
What is the purpose of this trial?
The goal of this research study is to determine whether hormonal therapies used early in the course of prostate cancer could increase the amount of Prostate-Specific Membrane Antigen (PSMA) as detected by PET/CT scans for participants with recurrent prostate cancer. This study will measure PSMA levels using standard PET/CT scans and participants will receive standard-of-care androgen receptor antagonist monotherapy. The names of the treatment interventions involved in this study are: * Androgen receptor antagonist monotherapy. * PSMA PET/CT scan It is expected that about 15 people will take part in this research study. Participation in this research study is expected to last about 4 weeks.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop your current medications, but you must be suitable for androgen receptor antagonist therapy and not have any drug interactions with the study medications.
What data supports the effectiveness of the drugs Apalutamide, Darolutamide, and Enzalutamide for prostate cancer?
Research shows that Darolutamide, Apalutamide, and Enzalutamide are effective in treating prostate cancer. Darolutamide has been shown to reduce tumor growth and improve survival in prostate cancer models. Apalutamide and Enzalutamide have also improved survival rates in patients with castration-resistant prostate cancer.12345
Is darolutamide safe for humans?
What makes the drug darolutamide unique for prostate cancer treatment?
Eligibility Criteria
Men aged 40+ with prostate cancer previously treated but now showing rising PSA levels indicating recurrence. They must have a PSMA PET/CT scan suggesting recurrent cancer, normal testosterone levels, and be prescribed standard AR antagonist therapy (apalutamide, darolutamide, or enzalutamide) by their doctor.Inclusion Criteria
My doctor has prescribed me a specific prostate cancer medication.
My scan shows at least one area that might mean my prostate cancer has come back.
I am over 40, had prostate cancer treatment, and my PSA levels are rising.
See 1 more
Exclusion Criteria
I cannot receive AR antagonist therapy.
My condition requires urgent treatment due to severe symptoms or high disease burden.
I am not taking older AR blockers like bicalutamide for my condition.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1 week
1 visit (in-person)
Treatment
Participants receive androgen receptor antagonist monotherapy and undergo PSMA PET/CT scans
4 weeks
2 visits (in-person) at weeks 1 and 4
Follow-up
Participants are monitored for safety and effectiveness after treatment
2 weeks
1 visit (in-person)
Treatment Details
Interventions
- Apalutamide [Erleada], darolutamide [Nubeqa], or enzalutamide [Xtandi] (Hormone Therapy)
- Prostate-Specific Membrane Antigen (PSMA) PET/CT Scan (Diagnostic Test)
Trial OverviewThis study tests if early hormonal therapies increase PSMA detected by PET/CT scans in men with recurring prostate cancer. About 15 participants will receive standard AR antagonist monotherapy and undergo PSMA level measurements for approximately 4 weeks.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Androgen Receptor Antagonist MonotherapyExperimental Treatment2 Interventions
* Participants will receive pre-determined doses of apalutamide, darolutamide, or enzalutamide per standard care.
* Participants will undergo Prostate-Specific Membrane Antigen (PSMA) PET/CT scans at weeks 1 and 4.
Apalutamide [Erleada], darolutamide [Nubeqa], or enzalutamide [Xtandi] is already approved in United States, United States, United States, European Union, European Union, European Union for the following indications:
🇺🇸 Approved in United States as Xtandi for:
- Nonmetastatic castration-resistant prostate cancer
- Metastatic castration-resistant prostate cancer
- Nonmetastatic castration-sensitive prostate cancer with biochemical recurrence
🇺🇸 Approved in United States as Erleada for:
- Nonmetastatic castration-resistant prostate cancer
- Metastatic castration-sensitive prostate cancer
🇺🇸 Approved in United States as Nubeqa for:
- Nonmetastatic castration-resistant prostate cancer
🇪🇺 Approved in European Union as Xtandi for:
- Metastatic castration-resistant prostate cancer
- Nonmetastatic castration-resistant prostate cancer
🇪🇺 Approved in European Union as Erleada for:
- Nonmetastatic castration-resistant prostate cancer
🇪🇺 Approved in European Union as Nubeqa for:
- Nonmetastatic castration-resistant prostate cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Beth Israel Deaconess Medical CenterBoston, MA
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Who Is Running the Clinical Trial?
Beth Israel Deaconess Medical CenterLead Sponsor
Dana-Farber Cancer InstituteCollaborator
References
Darolutamide: First Approval. [2020]Darolutamide (NUBEQA™) is a structurally distinct non-steroidal androgen receptor antagonist being developed by Orion and Bayer as a treatment for prostate cancer. Based on positive results in the phase III ARAMIS trial, darolutamide was recently approved in the USA for the treatment of men with non-metastatic castration-resistant prostate cancer. This article summarizes the milestones in the development of darolutamide leading to this first approval.
Darolutamide is a potent androgen receptor antagonist with strong efficacy in prostate cancer models. [2020]Darolutamide is a novel androgen receptor (AR) antagonist with a distinct chemical structure compared to other AR antagonists and currently in clinical Phase 3 trials for prostate cancer. Using cell-based transactivation assays, we demonstrate that darolutamide, its diastereomers and its main metabolite keto-darolutamide are strong, competitive antagonists for AR wild type, and also for several mutants identified in prostate cancer patients for which other AR antagonists show reduced antagonism or even agonism. Darolutamide, its two diastereomers and main metabolite are also strong antagonists in assays measuring AR N/C interaction and homodimerization. Molecular modeling suggests that the flexibility of darolutamide allows accommodation in the W742C/L mutated AR ligand-binding pocket while for enzalutamide the loss of the important hydrophobic interaction with W742 leads to reduced AR interaction. This correlates with an antagonistic pattern profile of coregulator recruitment for darolutamide. In vitro efficacy studies performed with androgen-dependent prostate cancer cell lines show that darolutamide strongly reduces cell viability and potently inhibits spheroid formation. Also, a marked down-regulation of androgen target genes paralleled by decreased AR binding to gene regulatory regions is seen. In vivo studies reveal that oral dosing of darolutamide markedly reduces growth of the LAPC-4 cell line-derived xenograft and of the KuCaP-1 patient-derived xenograft. Altogether, these results substantiate a unique antagonistic profile of darolutamide and support further development as a prostate cancer drug.
Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. [2022]In SPARTAN, apalutamide improved metastasis-free and overall survival for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) with a prostate-specific antigen doubling time of ≤10 mo.
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.
The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer. [2022]Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naïve metastatic castration-resistant prostate cancer.
Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. [2022]Oral darolutamide (Nubeqa™) is a novel second-generation, nonsteroidal, selective androgen receptor (AR) inhibitor indicated for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). In the pivotal multinational, phase 3 ARAMIS trial in men with nmCRPC, relative to placebo plus ongoing androgen deprivation therapy (ADT), darolutamide (+ ADT) significantly prolonged metastasis-free survival (MFS) at the time of the primary analysis and overall survival (OS) at the time of the final OS analysis and was generally well tolerated in extended follow-up. Albeit long-term data from the real-world setting are required to fully define the safety profile of darolutamide, current evidence from the final ARAMIS analysis indicates that darolutamide has a low propensity for CNS-related adverse events (AEs) associated with other currently approved second-generation AR inhibitors. Given the efficacy and safety evidence from the final ARAMIS analysis and the key role of second-generation AR inhibitors in the management of nmCRPC, darolutamide + ADT represents an important emerging option for the treatment of men with nmCRPC who are at high risk of developing metastatic prostate cancer.
Apalutamide: First Global Approval. [2019]Apalutamide (ErleadaTM) is a next-generation oral androgen receptor (AR) inhibitor that is being developed by Janssen for the treatment of prostate cancer (PC). It binds directly to the ligand-binding domain of the AR and blocks the effects of androgens. In February 2018, apalutamide received its first global approval in the USA for the treatment of non-metastatic castration-resistant PC (nmCRPC). Apalutamide is undergoing phase III investigation in chemotherapy-naive patients with metastatic CRPC (in combination with abiraterone acetate plus prednisone), patients with high-risk localized or locally advanced PC receiving primary radiation therapy, and in patients with metastatic hormone-sensitive PC and biochemically-relapsed PC. This article summarizes the milestones in the development of apalutamide leading to this first approval in nmCRPC.
Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. [2021]Apalutamide (Erleada®) is an oral selective androgen receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. It is approved in the EU and the USA for the treatment of adult men with metastatic castration-sensitive prostate cancer (mCSPC). In a multinational, phase III study (TITAN) in this patient population, the addition of apalutamide (240 mg once daily) to androgen deprivation therapy (ADT) significantly improved median radiographic progression-free survival (rPFS), median overall survival (OS) and the median time to cytotoxic chemotherapy, while maintaining health-related quality of life (HR-QOL) and not substantially differing from placebo plus ADT in safety. Although mature OS data are awaited with interest, the addition of apalutamide to ADT extends the treatment options available for standard of care in adult men with mCSPC.
Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. [2022]Darolutamide is a structurally unique androgen-receptor antagonist that is under development for the treatment of prostate cancer. We evaluated the efficacy of darolutamide for delaying metastasis and death in men with nonmetastatic, castration-resistant prostate cancer.