Darolutamide + SBRT for Prostate Cancer
Recruiting in Palo Alto (17 mi)
+9 other locations
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Sir Mortimer B. Davis - Jewish General Hospital
Must be taking: LHRH agonists
Must not be taking: AR inhibitors, Opiate analgesics
Disqualifiers: Severe disease, Metastasis, Other malignancy, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests a combination of precise radiation therapy and a hormone-blocking drug in prostate cancer patients with limited spread. It aims to control the disease and delay more toxic treatments. The approach targets small areas of cancer spread and blocks the cancer's growth signals. The hormone-blocking drug is a novel treatment approved for specific prostate cancer cases.
Do I have to stop taking my current medications for this trial?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot use certain treatments like opiate analgesics for prostate cancer pain, estrogens, AR inhibitors, systemic biologic therapy, investigational agents, or herbal products with hormonal activity within 4 weeks of enrollment. It's best to discuss your specific medications with the trial team.
What data supports the idea that Darolutamide + SBRT for Prostate Cancer is an effective treatment?
The available research shows that Darolutamide, when used with other therapies, has been effective in treating prostate cancer. In the ARAMIS trial, Darolutamide combined with ongoing hormone therapy significantly delayed the spread of cancer and improved survival in patients with non-metastatic prostate cancer. Additionally, in another trial, Darolutamide combined with hormone therapy and chemotherapy improved survival in patients with metastatic prostate cancer. These results suggest that Darolutamide is a promising option for treating prostate cancer, especially when combined with other treatments.
12345What safety data exists for Darolutamide and SBRT in prostate cancer treatment?
Darolutamide, an androgen receptor inhibitor, has been studied in various trials for prostate cancer. In the ARAMIS trial for non-metastatic castration-resistant prostate cancer (nmCRPC), it was well tolerated with a low propensity for CNS-related adverse events. In combination with androgen deprivation therapy (ADT) and docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC), it showed a manageable tolerability profile with adverse events consistent with those of ADT and docetaxel. However, specific safety data for the combination of Darolutamide and Stereotactic Body Radiation Therapy (SBRT) is not detailed in the provided research.
13567Is the drug Darolutamide a promising treatment for prostate cancer?
Yes, Darolutamide is a promising drug for prostate cancer. It has shown to improve survival rates in patients with advanced prostate cancer when used with other treatments. It is also effective against certain resistant forms of the disease and has a favorable safety profile.
12578Eligibility Criteria
Men with advanced prostate cancer that hasn't spread widely (≤5 sites, ≤4 in one organ excluding the brain) and is resistant to hormone therapy but has not metastasized according to standard scans. Participants must have a good performance status, be able to take oral medication, and have no recent other cancers or severe diseases. They should not have had certain previous treatments for prostate cancer.Inclusion Criteria
My prostate cancer is confirmed and does not have certain aggressive features.
I have 5 or fewer cancer spread sites, and none have been treated with radiation.
M0CRPC at study entry defined as follows: Ongoing androgen deprivation therapy with a LHRH agonist or bilateral orchiectomy (i.e., surgical or medical castration); Serum testosterone level ≤ 1.7 nmol/L (50 ng/dL) at the Screening visit; PSA progression defined by a minimum of two subsequent rising PSA levels with an interval of ≥ 1 week between each determination. Patients who received an anti-androgen must have progression after withdrawal (≥ 4 weeks since last flutamide or ≥ 6 weeks since last bicalutamide or nilutamide). The PSA value at the Screening visit should be ≥ 2 μg/L (2 ng/mL) PSA doubling time of 10 months or less, M0 assessed by conventional imaging (CT/MRI + bone scan). Prior cytotoxic chemotherapy for prostate cancer in adjuvant setting post radical therapy is allowed; Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or Karnofsky performance status of > 80% or higher; Estimated life expectancy of ≥ 6 months; Ability to swallow the study drug whole and comply with study. Patients should not have been previously exposed to other ARATs (Abiraterone, Enzalutamide, Apalutamide)
Exclusion Criteria
Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment; Presence of distant metastasis, including previously treated (clinical stage M1) is exclusive, however isolated pelvic nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion criteria. History of another malignancy within the previous 5 years other than curatively treated non-melanoma skin cancer; Absolute neutrophil count < 1,500/μL, platelet count < 100,000/μL, or hemoglobin < 5.6 mmol/L (9 g/dL) at the Screening visit (NOTE: patients may not have received any growth factors within 7 days or blood transfusions within 28 days of the hematologic laboratory values obtained at the Screening visit); Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal and total bilirubin > 1.5 times the upper limit of normal at the Screening visit; Creatinine > 2 times the upper limit of normal at the Screening visit; Clinically significant cardiovascular disease including: Stroke or myocardial infarction within 6 months; Uncontrolled angina within 6 months; Coronary/peripheral artery bypass graft within 6 months; Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within three months results in a left ventricular ejection fraction that is ≥ 45%; History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place; Uncontrolled hypertension as indicated by a resting systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg at screening. Patients may be re-screened after adjustments of antihypertensive medications; Bradycardia as indicated by a heart rate of < 50 beats per minute on the Screening ECG; Gastrointestinal disorder or procedure which expects to interfere significantly with absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months); Major surgery within 4 weeks of enrollment (Day 1 Visit); Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease Use of opiate analgesics (eg. morphine, fentanyl, etc.) for pain from prostate cancer within 4 weeks of enrollment (Day 1 visit). This does not apply to non-morphine drugs like codeine; Radiation therapy for treatment of the primary tumor within 3 weeks of enrollment (Day 1 visit); Radiation or radionuclide therapy for treatment of metastasis; Primary disease not treated; Hormone naïve prostate cancer patients; Treatment with estrogens or AR inhibitors (bicalutamide, flutamide, nilutamide, cyproterone acetate) within 4 weeks of enrollment (Day 1 visit); Treatment with systemic biologic therapy for prostate cancer (other than approved bone targeted agents and GnRH-analogue therapy) or other agents with anti-tumour activity within 4 weeks of enrollment (Day 1 visit); Prior use of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, enzalutamide, Apalutamide, TAK-700, TAK-683, TAK-448) or targets the androgen receptor (e.g., BMS 641988) on clinical trials; Participation in a previous clinical trial of darolutamide, where the patient has received darolutamide. If patient has received placebo and it is known, this may not apply; Known or suspected contraindications or hypersensitivity to darolutamide or GnRH agonists or any of the components of the formulations; Use of an investigational agent within 4 weeks of enrollment (Day 1 visit); Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within four weeks of enrollment (Day 1 visit); Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data; Unable to swallow study medications and comply with study requirements
I have more than 5 cancer spread sites or had radiation in the same area before.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Initial Treatment
Participants receive LHRH agonist in combination with darolutamide
Until progression to oligometastases
Regular PSA testing every 6-12 weeks and re-imaging every 6 months
Ablative Therapy
Participants with oligoprogression receive SBRT or surgery as an ablative therapy
Varies based on treatment response
Follow-up
Participants are monitored for safety and effectiveness after treatment
5 years
Re-imaging at symptom appearance or PSA progression
Participant Groups
The trial tests if adding SBRT (a type of precise radiation therapy) to Darolutamide (a drug blocking male hormones that can fuel prostate cancer growth) can delay the need for more aggressive therapies in men whose prostate cancer is progressing despite treatment but hasn't spread extensively.
1Treatment groups
Experimental Treatment
Group I: Darolutamide (BAY1841788)+ SBRTExperimental Treatment2 Interventions
CRPC subjects will receive LHRH agonist in combination with the new generation of hormonal therapy Darolutamide (300mg).
Subjects who progress on LHRH + Darolutamide and develop oligometastases will receive SBRT
Darolutamide (BAY1841788) is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Nubeqa for:
- Non-metastatic castration-resistant prostate cancer (nmCRPC)
🇪🇺 Approved in European Union as Nubeqa for:
- Non-metastatic castration-resistant prostate cancer (nmCRPC)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Centre hospitalier de l'Université de Montréal (CHUM)Montreal, Canada
Prostate Cancer CentreCalgary, Canada
Centre of Applied Urology ResearchHalifax, Canada
Hôpital Fleurimont (CHUS)Sherbrooke, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
Sir Mortimer B. Davis - Jewish General HospitalLead Sponsor
References
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 (ODM-201) for the treatment of prostate cancer. [2018]Androgen deprivation therapy (ADT) is a mainstay initial treatment for advanced hormone-sensitive prostate cancer (HSPC), but disease progression to castration-resistant prostate cancer (CRPC) invariably occurs when patients do not succumb to another disease or comorbidity. Recognition that the androgen receptor (AR) axis continues to drive disease progression has led to the development of several AR-directed approved agents, including abiraterone acetate and enzalutamide. An investigational agent, darolutamide (ODM-201, BAY-1841788), has completed early-phase clinical trials, and two global phase III trials are currently accruing patients. Areas covered: The unmet clinical need, pharmacokinetics, preclinical development, and clinical efficacy and safety of darolutamide for the treatment of advanced prostate cancer are reviewed. The design of two ongoing phase III trials (ARAMIS and ARASENS) of darolutamide in men with non-metastatic CRPC and metastatic HSPC, respectively, are also discussed. Expert opinion: Darolutamide is an oral, investigational, high-affinity AR antagonist which has activity against known AR mutants that confer resistance to other second-generation antiandrogens, has minimal blood-brain barrier penetration, and does not significantly increase serum testosterone. These features may offer potential advantages over the second-generation antiandrogens. In the phase I/II ARADES trial, darolutamide demonstrated promising antitumor activity and a favorable safety profile in men with metastatic CRPC.
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.
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.
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 for treatment of castration-resistant prostate cancer. [2020]Darolutamide is a novel, nonsteroidal androgen receptor (AR)-signaling inhibitor. It serves as a second-generation antiandrogen and is currently indicated for the treatment of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). The product was approved by the United States Food and Drug Administration (FDA) in July 2019 and by the Japanese Ministry of Health, Labour and Welfare (MHLW) in January 2020 for the treatment of men with nmCRPC, and is awaiting approval in the E.U. for the same indication. This review will cover the background, preclinical development, safety, pharmacokinetics, pharmacodynamics and clinical studies that led to the approval of darolutamide. The key clinical data, ongoing trials and future directions for darolutamide are also discussed herein.
Clinical Pharmacokinetics of the Androgen Receptor Inhibitor Darolutamide in Healthy Subjects and Patients with Hepatic or Renal Impairment. [2022]Darolutamide is a second-generation androgen receptor inhibitor approved for the treatment of nonmetastatic castration-resistant prostate cancer at a dosage of 600 mg orally twice daily.
Using darolutamide in advanced prostate cancer: How I Do It. [2021]Darolutamide is a nonsteroidal androgen inhibitor FDA approved for the treatment of castration-resistant non-metastatic prostate cancer (nmCRPC). After decades of offering androgen deprivation therapy (ADT) alone or first-generation androgen receptor blockers for patients whose PSA was rising despite castrate levels of testosterone, there are now three different treatment options to add to ADT. These include apalutamide approved in February 2018, enzalutamide FDA approved in June 2018, and darolutamide approved July 2019. Each of these androgen receptor pathway blockers, when added to ADT or surgical orchiectomy, prolongs metastasis-free-survival (MFS) and median survival (MS). This paper focuses on the use of the newest approved agent in this class, darololutmide.