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~24 spots leftby Nov 2027

Darolutamide + SBRT for Prostate Cancer

Recruiting at9 trial locations

Overseen byDr. Tamim Niazi, MDCM

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.¹ ² ³ ⁴ ⁵

What 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.¹ ³ ⁵ ⁶ ⁷

Is 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.¹ ² ⁵ ⁷ ⁸

Research Team

Dr. Tamim Niazi, MDCM

Principal Investigator

Jewish General Hospital

Eligibility 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

Treatment Details

Interventions

Darolutamide (BAY1841788) (Androgen Receptor Inhibitor)
SBRT (Radiation)

Trial OverviewThe 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.

Participant Groups

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

Sir Mortimer B. Davis - Jewish General Hospital

Lead Sponsor

Trials

Recruited

25,800+

Dr. Lucie Opatrny

Sir Mortimer B. Davis - Jewish General Hospital

President and Executive Director since 2023

MDCM and Master's in Epidemiology and Biostatistics from McGill University

Dr. Guy Rouleau

Sir Mortimer B. Davis - Jewish General Hospital

Chief Medical Officer since 2023

MD from McGill University

Findings from Research

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]

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]

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]