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

Recruiting in Palo Alto (17 mi)

+96 other locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: University of Sydney

Stay on your current meds

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 6 jurisdictions

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

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

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

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.

+4 more

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

Participant Groups

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.

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.

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: