Darolutamide + Relugolix 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: AdventHealth
Must not be taking: Chemotherapy, Radiotherapy, Antivirals, others
Disqualifiers: Stroke, Myocardial infarction, Angina, others
Stay on Your Current Meds
No Placebo Group
Trial Summary
What is the purpose of this trial?The goal of this clinical trial is to determine the safety and feasibility of a new combination of darolutamide and relugolix as neoadjuvant therapy preceding radical prostatectomy (RP) for high-risk prostate cancer (PCa) in adult males.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, if you are on drugs that strongly affect liver enzymes (CYP3A4), you may need to stop or switch them before starting the trial. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug Darolutamide for prostate cancer?
Darolutamide has been shown to improve survival in men with non-metastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer when used with other therapies, according to clinical trials. It is generally well-tolerated and has a low risk of causing side effects related to the brain.
12345Is the combination of Darolutamide and Relugolix safe for humans?
Darolutamide has been shown to be generally well tolerated in clinical trials for prostate cancer, with a low risk of central nervous system side effects and manageable overall side effects. It is important to note that dose adjustments may be necessary for patients with kidney or liver issues.
12346How is the drug combination of Darolutamide and Relugolix unique for prostate cancer treatment?
The combination of Darolutamide and Relugolix for prostate cancer is unique because Darolutamide is a novel androgen receptor inhibitor that has shown effectiveness in both metastatic and non-metastatic prostate cancer, while Relugolix is an oral medication that reduces testosterone levels, potentially offering a more convenient and less invasive option compared to traditional hormone therapies.
12357Eligibility Criteria
Men over 18 with high-risk prostate cancer who can swallow pills and have good performance status (able to carry out daily activities). They must have adequate organ function, be candidates for surgery to remove the prostate, and not have had certain treatments or other cancers recently.Inclusion Criteria
I am fully active or can carry out light work.
I am eligible for radical prostatectomy.
I am a man aged 18 or older.
+5 more
Exclusion Criteria
I haven't had chemotherapy or radiotherapy in the last 4 weeks.
Histologic variants comprising more than 50% of the sample as determined by pathology review
Receiving any other investigational agents
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Neoadjuvant Treatment
Participants receive a combination of darolutamide and relugolix as neoadjuvant therapy before radical prostatectomy
12 weeks
Radical Prostatectomy
Participants undergo radical prostatectomy following neoadjuvant treatment
Follow-up
Participants are monitored for safety and effectiveness after treatment
8 weeks
Participant Groups
The trial is testing a new combination of two drugs, darolutamide and relugolix, given before surgery to remove the prostate in men with aggressive prostate cancer. The aim is to see if it's safe and doable as a pre-surgery treatment.
1Treatment groups
Experimental Treatment
Group I: Combination Therapy ArmExperimental Treatment3 Interventions
This arm is designed to evaluate the safety and feasibility of the combination therapy using darolutamide and relugolix as neoadjuvant treatment before radical prostatectomy (RP) in patients with high-risk prostate cancer (PCa).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
AdventHealth OrlandoOrlando, FL
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Who Is Running the Clinical Trial?
AdventHealthLead Sponsor
BayerIndustry Sponsor
Sumitomo Pharma SwitzerlandCollaborator
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: A Review in Metastatic Hormone-Sensitive Prostate Cancer. [2023]Darolutamide (NUBEQA®) is an oral androgen receptor inhibitor (ARi) that is approved for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT) and docetaxel. In a pivotal trial, darolutamide plus ADT and docetaxel was superior to placebo plus ADT and docetaxel in prolonging the primary endpoint of overall survival, with improvements also reported in most secondary endpoints. Treatment with darolutamide plus ADT and docetaxel was associated with a manageable tolerability profile. Furthermore, the adverse events reported with darolutamide plus ADT and docetaxel were generally consistent with the safety profiles previously reported for ADT and docetaxel. Darolutamide expands the availability of treatment options in mHSPC and may be useful as a treatment for high-volume disease (typically defined as ≥ 4 bone metastases with spread outside of the pelvis and vertebral column).
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.
Clinical Pharmacokinetics and Pharmacodynamics of the Next Generation Androgen Receptor Inhibitor-Darolutamide. [2023]Darolutamide is a next-generation androgen receptor signaling inhibitor (ARSI) currently approved for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone sensitive prostate cancer (mHSPC). Studies suggest that darolutamide also has the potential to be used to treat other stages of prostate cancer (PC), suggesting that its indications will broaden in the near future. Since ARSIs show similar efficacy for the treatment of PC, pharmacokinetic properties of these drugs and patient characteristics could help physicians decide which drug to select. This review provides an overview of the pharmacokinetic and pharmacodynamic properties of darolutamide. One of the most important pharmacological advantages of darolutamide is its low brain distribution and therefore limited seizure potential and central nervous system adverse effects. In addition, darolutamide has little drug-drug interaction potential and is unlikely to alter the exposure of other cytochrome P450 or P-glycoprotein substrates. Nevertheless, it may significantly increase the exposure of breast cancer resistant protein (BCRP) substrates. The limited solubility and bioavailability of darolutamide increases when taken together with food, regardless of the fat content. Darolutamide is excessively metabolized by oxidation and glucuronidation and excreted in the urine and feces. For this reason, dose reduction is required in patients with moderate and severe renal or severe hepatic impairment. Although no exposure-response relationship was observed with darolutamide, less advanced stages of PC showed better PSA response on treatment. Overall, darolutamide has some advantageous pharmacological properties that may lead to its preferred use, when broader registered, in selected patients across different disease stages.
Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. [2023]Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown.
Phase 1 study of darolutamide (ODM-201): a new-generation androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer. [2023]This trial assessed the safety, pharmacokinetics, and efficacy of darolutamide (ODM-201), a new-generation nonsteroidal androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC).
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.