Darolutamide + SBRT for Prostate Cancer

Recruiting at 12 trial locations

Overseen By Paola Diego

Age: 18+

Sex: Male

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating prostate cancer that hasn't spread to distant parts of the body but progresses despite current hormone treatments. It combines Darolutamide, a type of hormone therapy, with focused radiation therapy called SBRT to determine if this duo can delay the need for more aggressive treatments. Men with prostate cancer who are undergoing hormone therapy and show specific signs of cancer progression, such as rising PSA levels (a protein marker), might be suitable candidates. The trial aims to determine if this combined treatment can effectively manage the cancer and improve outcomes for these patients.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that patients usually tolerate darolutamide well. Common side effects include rash, tiredness, hot flashes, and sweating. About 7.4% of patients experienced moderate side effects, while serious ones were rare.

Long-term studies suggest that SBRT, a precise radiation therapy, has manageable side effects. It might cause some irritation, but many patients do not experience severe problems.

Both treatments have demonstrated safety in other situations, with side effects often being mild. While no treatment is without risk, evidence suggests these are relatively safe options. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment using Darolutamide for prostate cancer because it represents a new approach to tackling the disease. Unlike most standard treatments that rely heavily on hormone therapy alone, Darolutamide is a next-generation hormonal therapy that targets androgen receptors more precisely, which may lead to fewer side effects and more effective disease control. Additionally, combining Darolutamide with stereotactic body radiation therapy (SBRT) offers a targeted attack on cancer cells, potentially improving outcomes for patients who have developed oligometastases. This combination could offer a more comprehensive treatment strategy, possibly leading to better management of the cancer.

What evidence suggests that Darolutamide + SBRT might be an effective treatment for prostate cancer?

Research has shown that combining darolutamide with androgen deprivation therapy (ADT) can extend the time patients live without cancer progression, improving this outcome by 40%. Studies also indicate that darolutamide is generally safe, with most side effects being mild. In this trial, participants will receive a combination of darolutamide and stereotactic body radiation therapy (SBRT). SBRT offers strong long-term control of prostate cancer, performing as well as other radiation types but with fewer treatment sessions. Together, these treatments show promise in effectively managing prostate cancer. ^{2 3 4 5 6}

Who Is on the Research Team?

Dr. Tamim Niazi, MDCM

Principal Investigator

Jewish General Hospital

Are You a Good Fit for This Trial?

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

I have 5 or fewer cancer spread sites, and none have been treated with radiation.

My prostate cancer is confirmed and does not have certain aggressive features.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide (BAY1841788)
• SBRT

Trial Overview 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.

How Is the Trial Designed?

Group I: Darolutamide (BAY1841788)+ SBRT Experimental Treatment 2 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)

Who Is Running the Clinical Trial?

Sir Mortimer B. Davis - Jewish General Hospital

Lead Sponsor

Trials

61

Recruited

25,800+

Published Research Related to This Trial

Darolutamide is an FDA-approved nonsteroidal androgen inhibitor specifically for treating castration-resistant non-metastatic prostate cancer, providing a new option for patients whose PSA levels are rising despite low testosterone.

When used alongside androgen deprivation therapy (ADT), darolutamide, like other newer agents in its class, has been shown to prolong metastasis-free survival and median survival, making it an effective treatment choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using darolutamide in advanced prostate cancer: How I Do It. Hamilton, J.[2021]

Darolutamide (NUBEQA™) is a new non-steroidal androgen receptor antagonist approved for treating non-metastatic castration-resistant prostate cancer in men, based on positive results from the phase III ARAMIS trial.

The approval of darolutamide marks a significant milestone in prostate cancer treatment, highlighting its efficacy and safety profile as demonstrated in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: First Approval. Markham, A., Duggan, S.[2020]

Darolutamide is an investigational oral medication that acts as a high-affinity androgen receptor antagonist, showing promising antitumor activity and a favorable safety profile in early-phase trials for advanced prostate cancer.

Unlike other antiandrogens, darolutamide has minimal penetration of the blood-brain barrier and does not significantly increase serum testosterone levels, which may provide advantages in treating patients with resistance to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide (ODM-201) for the treatment of prostate cancer. Shore, ND.[2018]

Darolutamide is a new nonsteroidal androgen receptor inhibitor approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), showing promise as a second-generation antiandrogen.

The drug received FDA approval in July 2019 and is currently undergoing further evaluation in the E.U., highlighting its potential as a significant treatment option for men with nmCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide for treatment of castration-resistant prostate cancer. Rhea, LP., Mendez-Marti, S., Aragon-Ching, JB.[2020]

Darolutamide, taken at 600 mg twice daily, shows predictable linear pharmacokinetics with a half-life of 13 hours, allowing for consistent inhibition of androgen receptor signaling in patients with nonmetastatic castration-resistant prostate cancer.

The absorption of darolutamide is significantly improved when taken with food, increasing its bioavailability from about 30% to 60-75%, which is important for optimizing treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics of the Androgen Receptor Inhibitor Darolutamide in Healthy Subjects and Patients with Hepatic or Renal Impairment. Zurth, C., Nykänen, P., Wilkinson, G., et al.[2022]

In the phase 3 ARAMIS trial, darolutamide significantly improved metastasis-free survival and overall survival in men with non-metastatic castration-resistant prostate cancer compared to placebo, indicating its efficacy when combined with ongoing androgen deprivation therapy.

Darolutamide was generally well tolerated, showing a low risk of central nervous system-related side effects, which is a common concern with other second-generation androgen receptor inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. Scott, LJ.[2022]

In a phase 3 trial involving 1509 men with nonmetastatic, castration-resistant prostate cancer, darolutamide significantly improved metastasis-free survival, with a median of 40.4 months compared to 18.4 months for placebo (hazard ratio 0.41).

The safety profile of darolutamide was comparable to placebo, with similar rates of adverse events and no increased risk of serious side effects like seizures or cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. Fizazi, K., Shore, N., Tammela, TL., et al.[2022]

Darolutamide, an oral androgen receptor inhibitor, significantly improves overall survival in patients with metastatic hormone-sensitive prostate cancer when combined with androgen deprivation therapy and docetaxel, compared to placebo.

The treatment with darolutamide has a manageable safety profile, with adverse events aligning with those typically seen in androgen deprivation therapy and docetaxel, making it a viable option for patients with high-volume disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: A Review in Metastatic Hormone-Sensitive Prostate Cancer. Lee, A.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40310703/

Real-world effectiveness of darolutamide in metastatic ... Darolutamide suppressed serum PSA levels by >50% in 5/44 M1-CRPC patients (11.4%), all previously 2GARA-naïve. M1-CRPC patients resistant only ...

2. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-metastatic-castration-sensitive-prostate-cancer

FDA approves darolutamide for metastatic castration ... Treatment with darolutamide resulted in a statistically significant improvement in rPFS compared to placebo. Median rPFS was not reached in the ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e17108

Real world outcomes of darolutamide efficacy and safety in ... Common side effects included rash, fatigue, hot flushes, and sweating, with 7.4% (n=14) experiencing grade 2 adverse events and 0.5% (n=1) with ...

4. bayer.com bayer.com/en/us/news-stories/new-data-for-nubeqa

New Data for NUBEQA® Build on Safety and Efficacy ... NUBEQA (darolutamide) plus androgen deprivation therapy (ADT) improved radiological progression-free survival (rPFS) by 40% (HR 0.60; 95% CI: 0.44-0.80) and 70 ...

5. nature.com nature.com/articles/s41391-025-01047-7

DARolutamide ObservationaL (DAROL) study in patients ... Darolutamide showed consistent safety and effectiveness in DAROL vs ARAMIS. Most treatment-emergent adverse events were grade 1/2. Two-year ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37660438/

Efficacy and safety outcomes of darolutamide in patients ... Darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% versus placebo, with a favourable ...