What is the mechanism of action of this treatment?

Prostate cancer treatments often target the androgen receptor pathway, which is crucial for the growth and survival of prostate cancer cells. Androgen deprivation therapy (ADT) reduces androgen levels in the body, either through surgical castration or medications like luteinizing hormone-releasing hormone analogues (LHRHAs). Androgen receptor inhibitors, such as darolutamide, enzalutamide, and apalutamide, block the androgen receptor, preventing androgens from stimulating cancer cell growth. These treatments are vital for prostate cancer patients because they effectively slow disease progression and improve survival rates by targeting the hormonal drivers of cancer growth.

What side effects are associated with this type of intervention?

Common treatments for prostate cancer that involve androgen receptor inhibition, such as darolutamide, enzalutamide, and apalutamide, have several known side effects. Darolutamide is associated with fewer central nervous system side effects compared to enzalutamide and apalutamide, which can cause fatigue, seizures, and falls. When combined with androgen deprivation therapy (ADT) and docetaxel, these treatments can also lead to increased risks of severe myelosuppression, fatigue, peripheral edema, and gastrointestinal issues like diarrhea. It is important to monitor for these side effects and manage them appropriately in consultation with a healthcare provider.

What prior FDA approvals exist?

Enzalutamide and apalutamide are two FDA-approved androgen receptor inhibitors for the treatment of prostate cancer. Enzalutamide is approved for metastatic castration-resistant prostate cancer (CRPC) and has shown to increase median survival in clinical trials. Apalutamide is approved for both nonmetastatic and metastatic castration-sensitive prostate cancer (CSPC), demonstrating significant improvements in overall survival and progression-free survival. These drugs, like darolutamide, work by inhibiting the androgen receptor, which is crucial for the growth of prostate cancer cells.

What other types of research exist?

Promising alternatives to Darolutamide for prostate cancer treatment in 2024 include Enzalutamide, Apalutamide, and Abiraterone Acetate. These therapies have demonstrated efficacy in clinical trials for both hormone-sensitive and castration-resistant prostate cancer. Additionally, combination therapies involving PARP inhibitors like Olaparib and Niraparib with androgen deprivation therapy are emerging as effective options, particularly for patients with specific genetic mutations.

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Darolutamide + Standard Therapy for Prostate Cancer (DASL-HiCaP Trial)

Phase 3

Waitlist Available

Research Sponsored by University of Sydney

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

EITHER planned for primary RT and judged to be at very high risk for recurrence based on any of the following: Grade Group 5, Grade Group 4 AND one or more of the following: clinical T2b-4 OR MRI with seminal vesicle invasion OR extracapsular extension OR PSA* > 20ng/mL, Pelvic nodal involvement (involvement of lymph nodes (LNs) at or below the bifurcation of the aorta into the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or pathologically confirmed (PSMA PET alone is not considered enough if ≤ 10mm) OR Post-radical prostatectomy ≤ 365 days prior to randomisation and planned for RT with PSA* ≥ 0.1 ng/mL that has risen or remained stable (within ≤ 0.05 ng/mL) since a previous level at least 1 week earlier, judged to be at very high risk for recurrence based on any of the following: Grade Group 5, Grade Group 4 AND pT3a or higher, Pelvic nodal involvement (involvement of LNs at or below the bifurcation of the aorta into the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or pathologically confirmed (PSMA PET alone is not considered enough if ≤ 10mm) * This PSA level must be measured within 60 days prior to randomisation. However, if a participant has already commenced endocrine therapy (ET) for prostate cancer, this PSA level must be measured within 180 days prior to commencing ET.,Adequate bone marrow function: Haemoglobin ≥ 100g/L, white cell count (WCC) ≥ 4.0x109/L, absolute neutrophil count (ANC) ≥ 1.5x109/L and platelets > 100 x 109/L,Adequate liver function: alanine aminotransferase (ALT) < 2 x upper limit of normal (ULN) and total bilirubin < 1.5 x ULN, (or if total bilirubin is between 1.5 - 2 x ULN, they must have a normal conjugated bilirubin),Adequate renal function: calculated creatinine clearance > 30 mL/min (Cockroft-Gault),Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1,Study treatment both planned and able to start within 7 days after randomisation,Willing to complete health-related quality of life (HRQL) questionnaires UNLESS is unable to complete because of literacy or limited vision,Willing and able to comply with all study requirements, including standard of care treatment such as EBRT, timing and/or nature of required assessments,Signed, written informed consent

Men aged 18 years and older, with pathological diagnosis of adenocarcinoma of the prostate

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, an average of 5 years

Awards & highlights

Pivotal Trial

Summary

This trial is testing darolutamide, a new drug added to standard hormone therapy, in men with high-risk localized prostate cancer undergoing radiation. The goal is to see if this combination can better prevent the cancer from coming back and spreading compared to current treatments. Darolutamide works by blocking male hormones that help cancer grow, potentially reducing death rates from prostate cancer.

Who is the study for?

Men over 18 with high-risk localized prostate cancer, eligible for radiation therapy and at very high risk of recurrence. They must have a specific type of prostate cancer (adenocarcinoma), certain PSA levels, and no evidence of metastatic disease or previous potent AR inhibition treatments. Participants need good organ function, performance status, and must be willing to follow study procedures.

What is being tested?

The trial is testing the effectiveness of darolutamide in combination with standard hormone therapy using LHRHA and external beam radiotherapy in men undergoing treatment for very high-risk localized prostate cancer. The goal is to see if adding darolutamide helps prevent cancer from coming back.

What are the potential side effects?

Darolutamide may cause fatigue, digestive issues like nausea or diarrhea, skin rash, liver enzyme changes which could indicate liver damage, blood pressure changes, and can affect how other medications work.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am a man over 18 with a prostate cancer diagnosis.

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My kidneys work well enough, with a creatinine clearance over 30 mL/min.

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My liver tests are within the normal range.

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My blood tests show normal levels of hemoglobin, white cells, neutrophils, and platelets.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, an average of 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, an average of 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, an average of 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Metastasis-free survival

Secondary study objectives

Fear of cancer recurrence

Frequency and severity of adverse events (CTCAE v5.0, RTOG/EORTC acute/late radiation morbidity criteria)

Health-related quality of life

+5 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: DarolutamideExperimental Treatment3 Interventions

Darolutamide 600mg (2 x 300mg tablets) twice daily by mouth for 96 weeks, adherence monitored by participant report. All participants are treated with an LHRHA for 96 weeks from randomisation and external beam radiation therapy started within 8-24 weeks after randomisation.

Group II: PlaceboPlacebo Group3 Interventions

Placebo (2 tablets) twice daily by mouth for 96 weeks, adherence monitored by participant report. All participants are treated with an LHRHA for 96 weeks from randomisation and external beam radiation therapy started within 8-24 weeks after randomisation.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Darolutamide

2018

Completed Phase 2

~100

External Beam Radiotherapy

1995

Completed Phase 3

~440

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments often target the androgen receptor pathway, which is crucial for the growth and survival of prostate cancer cells. Androgen deprivation therapy (ADT) reduces androgen levels in the body, either through surgical castration or medications like luteinizing hormone-releasing hormone analogues (LHRHAs). Androgen receptor inhibitors, such as darolutamide, enzalutamide, and apalutamide, block the androgen receptor, preventing androgens from stimulating cancer cell growth. These treatments are vital for prostate cancer patients because they effectively slow disease progression and improve survival rates by targeting the hormonal drivers of cancer growth.