Darolutamide + Standard Therapy for Prostate Cancer

(DASL-HiCaP Trial)

Not currently recruiting at 100 trial locations

Overseen By DASL Trial Coordinator

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: University of Sydney

Must be taking: LHRHA

Must not be taking: Abiraterone, Enzalutamide

Disqualifiers: Metastatic disease, PSA > 100, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 96 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of darolutamide, a type of hormone therapy, when added to standard hormone therapy for men undergoing radiation treatment for localized prostate cancer with a high risk of recurrence. The study includes two groups: one receiving the experimental drug, darolutamide, and the other receiving a placebo, both alongside hormone therapy and radiation. Men diagnosed with prostate cancer at high risk of recurrence, who plan to receive radiation therapy and have not undergone certain previous treatments or conditions, might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for this trial?

The trial requires stopping certain medications before starting the study treatment. If you are taking a first-generation nonsteroidal antiandrogen (NSAA) or a 5-alpha reductase inhibitor, you must stop these before beginning the trial. The protocol does not specify other medications, so it's best to discuss with the study team.

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

Research has shown that darolutamide is generally safe and well-tolerated. Studies have found it significantly improves survival rates in prostate cancer patients. Most side effects are minor, such as fatigue or hot flashes. Serious side effects are rare, with less than 1% of patients experiencing severe reactions. This suggests darolutamide is a safe option for many patients when combined with other treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about darolutamide for prostate cancer because it targets androgen receptors in a novel way. Unlike many standard treatments that rely solely on hormone therapy to reduce androgen production, darolutamide directly blocks the androgen receptor, preventing cancer cells from growing and spreading. This dual action could potentially improve outcomes for patients, offering a more comprehensive approach than current therapies like androgen deprivation therapy and chemotherapy. Additionally, darolutamide has a favorable side effect profile, meaning it might be easier for patients to tolerate while maintaining effectiveness.

What evidence suggests that darolutamide might be an effective treatment for prostate cancer?

Research shows that darolutamide, one of the treatments in this trial, when combined with androgen deprivation therapy (ADT), can significantly improve outcomes for prostate cancer patients. Studies have found that darolutamide increased the time patients lived without their cancer worsening by 40% compared to a placebo. Simply put, patients experienced a longer period without cancer progression. In another study, 29% of men taking darolutamide with ADT saw their cancer worsen or passed away, compared to 42% of those not taking it. These findings suggest that darolutamide may control prostate cancer more effectively than standard treatment alone. Participants in this trial will receive either darolutamide or a placebo, alongside standard therapy with ADT and external beam radiation therapy. ^{2 3 5 6 7}

Who Is on the Research Team?

Christopher Sweeney

Principal Investigator

Dana-Farber Cancer Institute and Harvard Medical School

Tamim Niazi

Principal Investigator

Jewish General Hospital and McGill University

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

You are willing to complete HRQL questionnaires unless you are unable to complete due to literacy or limited vision.

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

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

Exclusion Criteria

Prostate cancer with predominant non-adenocarcinoma features (sarcomatoid or spindle cell or neuroendocrine small cell or squamous cell components or other non-adenocarcinoma),Involvement of LNs by conventional CT imaging superior to the common iliac artery bifurcation, and/or outside the pelvis (distant LNs). LN involvement is defined by histopathological confirmation, or by a short axis measurement > 10mm on standard imaging (CT or MRI, but not PET).,Evidence of metastatic disease. Minimum imaging requirements to exclude metastatic disease are diagnostic quality imaging of both the pelvis and the abdomen (CT or MRI), chest (CXR or CT), and a whole body radioisotope bone scan (WBBS).,If endocrine therapy (ET) had not started, imaging must be within 60 days prior to randomisation.,If ET has been started, imaging must have been performed no more than 60 days prior to starting ET and no more than 30 days after starting ET and prior to randomisation.,PSA > 100 ng/mL at any time,Any prior use of new generation potent AR inhibition (abiraterone, enzalutamide, apalutamide, darolutamide or similar agents).,Prior endocrine therapy for prostate cancer except for the following which are allowed: (i) LHRHA and/or (ii) a first-generation nonsteroidal antiandrogen (NSAA) are allowed if commenced no more than 90 days before randomisation. If an NSAA has been used, it must be stopped before starting study treatment with darolutamide/placebo; and Prior use of 5-alpha reductase inhibitor is allowed and if used it must be stopped before starting study treatment with darolutamide/placebo,Bilateral orchidectomy,Prior pelvic brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields that would preclude the required RT,History of Loss of consciousness or transient ischemic attack or stroke within 6 months prior to randomisation, or Significant cardiovascular disease within 6 months prior to randomisation: including myocardial infarction, unstable angina, congestive heart failure (NYHA grade II or greater), ongoing arrhythmias of Grade > 2 (CTCAE v5.0), thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism), coronary artery bypass graft. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.,Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of darolutamide, including difficulty swallowing tablets,History of another malignancy within 5 years prior to randomisation except for those malignancies treated with curative intent with a predicted risk of relapse of less than 10% including but not limited to non-melanoma carcinoma of the skin; or adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (i.e. Tis, Ta and low grade T1 tumours). All such cases with a history of malignancy within the last 5 years are to be discussed with study team before randomisation. Melanoma in-situ and other adequately treated in-situ neoplasms are not considered malignancies for the purposes of eligibility assessment.,Concurrent illness, including severe infection that might jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety (HIV infection is not an exclusion criterion if it is controlled with anti-retroviral drugs that are unaffected by concomitant darolutamide),Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse,Patients who are sexually active with women of child-bearing potential and not willing/able to use medically acceptable and highly effective forms of contraception during study treatment and for at least 4 weeks after completion of study treatment. Contraception must include: Condom use (also required if sexual partner is pregnant), and Additional birth control with low failure rate (less than 1% per year) when used consistently and correctly. E.g. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, true sexual abstinence. True sexual abstinence will only be an acceptable form of contraception when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study treatment, and withdrawal are not acceptable methods of contraception.,Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases,Major surgery within 21 days prior to randomisation,Patients with history of hypersensitivity to the study treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive darolutamide or placebo along with androgen deprivation therapy and radiation therapy

96 weeks

Regular visits for monitoring adherence and side effects

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Approximately 12-weekly visits for 2 years, then regular follow-up

Long-term follow-up

Participants are monitored for overall survival and prostate cancer-specific survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide
• External Beam Radiotherapy
• Luteinizing Hormone-Releasing Hormone Analog
• Placebo oral tablet

Trial Overview 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.

How Is the Trial Designed?

Group I: Darolutamide Experimental Treatment 3 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: Placebo Placebo Group 3 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.

External Beam Radiotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as External Beam Radiotherapy for:

• Cancer treatment including but not limited to breast cancer, lung cancer, prostate cancer, head and neck cancer

Approved in United States as External Beam Radiotherapy for:

• Cancer treatment including but not limited to breast cancer, lung cancer, prostate cancer, head and neck cancer

Approved in Canada as External Beam Radiotherapy for:

• Cancer treatment including but not limited to breast cancer, lung cancer, prostate cancer, head and neck cancer

Approved in Japan as External Beam Radiotherapy for:

• Cancer treatment including but not limited to breast cancer, lung cancer, prostate cancer, head and neck cancer

Approved in China as External Beam Radiotherapy for:

• Cancer treatment including but not limited to breast cancer, lung cancer, prostate cancer, head and neck cancer

Approved in Switzerland as External Beam Radiotherapy for:

• Cancer treatment including but not limited to breast cancer, lung cancer, prostate cancer, head and neck cancer

Who Is Running the Clinical Trial?

University of Sydney

Lead Sponsor

Trials

208

Recruited

417,000+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Prostate Cancer Clinical Trials Consortium

Collaborator

Trials

12

Recruited

7,400+

Cancer Trials Ireland

Collaborator

Trials

85

Recruited

25,600+

Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Collaborator

Trials

21

Recruited

7,000+

Published Research Related to This Trial

In a study of 215 patients with locally advanced prostate cancer, 97.5% of those treated with external beam radiation therapy (EBRT) showed no biochemical failure after a mean follow-up of 17.3 months, indicating high efficacy of the treatment protocol.

The study suggests that intermittent androgen ablation therapy after EBRT may be a viable option, although the follow-up period was short and further research is needed to confirm long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant endocrine therapy and external beam radiation therapy in men with locally advanced prostate cancer. Yamanaka, H., Ito, K., Naito, S., et al.[2013]

In a study of 46,325 men with high-risk prostate cancer, androgen deprivation therapy (ADT) improved overall survival for those receiving external beam radiation therapy (EBRT) alone, but not for those receiving combined EBRT and brachytherapy.

The findings suggest that while ADT is beneficial with EBRT, it may not enhance survival in patients treated with both EBRT and brachytherapy, highlighting the need for further research to evaluate the risks and benefits of ADT in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of Apparent Survival Benefit With Use of Androgen Deprivation Therapy in Patients With High-risk Prostate Cancer Receiving Combined External Beam Radiation Therapy and Brachytherapy. Yang, DD., Muralidhar, V., Mahal, BA., et al.[2018]

A survey of 42 North American genitourinary physicians revealed a significant divide in treatment recommendations for high-risk prostate cancer, with 45% supporting the addition of brachytherapy (BT) boost to external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT), while 55% preferred EBRT and ADT alone.

Experts in brachytherapy were much more likely to recommend the BT boost, indicating that physician expertise significantly influences treatment decisions, which may impact future clinical guidelines and studies in prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dramatically Polarized Opinion on the Role of Brachytherapy Boost in Management of High-risk Prostate Cancer: A Survey of North American Genitourinary Expert Radiation Oncologists. McClelland, S., Sandler, KA., Degnin, C., et al.[2019]

In a study of 585 high-risk prostate cancer patients treated with high-dose external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT), a biopsy Gleason score (bGS) of 8 to 10 was identified as the strongest predictor of biochemical relapse-free survival (bRFS), distant metastases-free survival (DMFS), and prostate cancer-specific mortality (PCSM).

The study found that the duration of ADT did not significantly impact patient outcomes, highlighting the importance of tumor characteristics over treatment length in predicting survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. Tendulkar, RD., Reddy, CA., Stephans, KL., et al.[2020]

A study of 1,825 men with prostate cancer treated with external beam radiation therapy (EBRT) found that location of treatment significantly influenced the level of adverse effects, with one regional cancer service reporting a higher 'big bother' rate (11.1%) compared to the rest of Victoria (4.8%).

The study indicates that while the technique of EBRT did not show a significant impact on patient outcomes over time, the variation in patient-reported adverse effects highlights the importance of monitoring and evaluating treatment locations for better patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of patient-reported quality of life outcomes after external beam radiation treatment for prostate cancer in Victoria: A cohort study by the Victorian Prostate Cancer Registry. Patabendi Bandarage, VR., Billah, B., Millar, JL., et al.[2018]

In a study of 173 patients with high-risk localized prostate cancer, long-term androgen deprivation therapy (ADT) for 36 months or more combined with external-beam radiotherapy (EBRT) significantly improved five-year progression-free survival rates (92.8%) compared to short-term ADT (72.9%).

Patients receiving short-term ADT experienced a higher incidence of cardiovascular toxicity (grade II or above) compared to those on long-term ADT, indicating that longer ADT may not only enhance survival but also have a more favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the duration of hormonal therapy following radiotherapy for localized prostate cancer. Okubo, M., Nakayama, H., Itonaga, T., et al.[2022]

Citations

1. 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 ...

2. 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 ...

3. 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 ...

4. 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 ...

5. nubeqa-us.com nubeqa-us.com/about-nubeqa/mcspc-study-results

Clinical Study | NUBEQA® (darolutamide) | Patient Website At the time of analysis, 29% (128 out of 446) of men taking NUBEQA + ADT had cancer worsening via scans or were no longer living compared to 42% (94 out of 223) ...

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 ...

7. 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 ...