Darolutamide + ADT for Prostate Cancer

(ARASTEP Trial)

Recruiting in Palo Alto (17 mi)

+359 other locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Bayer

Must be taking: Androgen deprivation therapy

Must not be taking: Second generation ARIs, CYP 17 inhibitors

Disqualifiers: Small cell carcinoma, Brain metastasis, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Researchers are looking for a better way to treat men at high-risk of biochemical recurrence (BCR) of prostate cancer. BCR means that in men who had prostate cancer and were treated by either surgery and/ or radiation therapy, the blood level of a specific protein called PSA rises. PSA is a marker of prostate cancer cells activity. The PSA increase means that the cancer has come back even though conventional imaging such as computed tomography (CT) scans, magnetic resonance imaging (MRI) and bone scans does not show any lesion of prostate cancer. Recently a more sensitive imaging method called prostate-specific membrane antigen \[PSMA\] positron emission tomography \[PET\]) /computed tomography \[CT\]) scan may identify prostate cancer lesions not detectable by conventional imaging. Men with BCR have a higher risk of their cancer spreading to other parts of the body, particularly when PSA levels raised to a certain limit within a short period of time after local therapies. Once the cancer spreads to other parts of the body, it can become even harder to treat. In men with prostate cancer, male sex hormones (also called androgens) like testosterone can help the cancer grow and spread. To reduce androgens levels in these patients, there are treatments that block androgens production in the body called androgen deprivation therapy (ADT). ADT is often used to stop prostate cancer. Another way to stop prostate cancer growth and spread is to block the action of androgen receptors on prostate cancer cells called androgen receptor inhibitors (ARIs). The new generation ARIs including darolutamide can block the action of androgens receptors and are available for the treatment of prostate cancer in addition to ADT. It is already known that men with prostate cancer benefit from these treatments. The main objective of this study is to learn if the combination of darolutamide and ADT prolongs the time that the participants live without their cancer getting worse, or to death due to any cause, compared to placebo (which is a treatment that looks like a medicine but does not have any medicine in it) and ADT given for a pre-specified duration of 24 months. To do this, the study team will measure the time from the date of treatment allocation to the finding of new cancer spread in the participants by using PSMA PET/CT, or death due to any cause. The PSMA PET/CT scans is performed using a radioactive substance called a "tracer" that specifically binds to the prostate-specific membrane antigen (PSMA) which is a protein often found in large amounts on prostate cancer cells. To avoid bias in treatment, the study participants will be randomly (by chance) allocated to one of two treatment groups. Based on the allocated treatment group, the participants will either take darolutamide plus ADT or placebo plus ADT twice daily as tablets by mouth. The study will consist of a test (screening) phase, a treatment phase and a follow-up phase. The treatment duration is pre-specified to be 24 months unless the cancer gets worse, the participants have medical problems, or they leave the study for any reason. In addition, image guided radiotherapy (IGRT) or surgery is allowed and your doctor will explain the benefits and risks of this type of therapy. During the study, the study team will: * take blood and urine samples. * measure PSA and testosterone levels in the blood samples * do physical examinations * check the participants' overall health * examine heart health using electrocardiogram (ECG) * check vital signs * check cancer status using PSMA PET/CT scans, CT, MRI and bone scans * take tumor samples (if required) * ask the participants if they have medical problems About 30 days after the participants have taken their last treatment, the study doctors and their team will check the participants' health and if their cancer worsened. The study team will continue to check this and regularly ask the participants questions about medical problems and subsequent therapies until they leave the study for any reason or until they leave the study for any reason or until the end of the study, whatever comes first.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have been treated with certain prostate cancer drugs like enzalutamide or abiraterone in the past 18 months, you may not be eligible to participate.

What data supports the effectiveness of the drug Darolutamide + ADT for prostate cancer?

Research shows that Darolutamide, when combined with androgen deprivation therapy (ADT), has been effective in increasing survival rates in patients with prostate cancer. In particular, it has been shown to prolong overall survival in metastatic hormone-sensitive prostate cancer and improve metastasis-free survival in non-metastatic castration-resistant prostate cancer. ^{1 2 3 4 5}

Is Darolutamide + ADT safe for humans?

Darolutamide, when used with androgen deprivation therapy (ADT), has been shown to have a manageable safety profile in clinical trials for prostate cancer. The side effects reported are generally consistent with those of ADT and other similar treatments, and it has a low risk of causing central nervous system-related side effects. ^{1 3 4 6 7}

What makes the drug darolutamide unique for prostate cancer treatment?

Darolutamide is a unique non-steroidal androgen receptor antagonist that, when combined with androgen deprivation therapy (ADT), offers a new option for treating non-metastatic castration-resistant prostate cancer by significantly prolonging metastasis-free survival and overall survival, with a lower risk of central nervous system side effects compared to other similar drugs. ^{1 3 4 6 8}

Eligibility Criteria

This trial is for men over 18 with hormone-sensitive prostate cancer who've had a rise in PSA levels after local treatments like surgery or radiation. They must be generally healthy, able to consent, and willing to use contraception. Men with certain types of aggressive prostate cancer, previous extensive treatments, or recent other cancers are excluded.

Inclusion Criteria

Screening values of: Alanine aminotransferase (ALT) ≤1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) ≤1.5 x ULN; Total bilirubin (TBL) ≤1.5 ULN, (except participants with a diagnosis of Gilbert's disease); Estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 m^2 calculated by the CKD-EPI formula

My prostate cancer was first treated with surgery, possibly followed by radiation, or just radiation.

Serum testosterone ≥150 ng/dL (5.2 nmol/L) (local or central values accepted)

Exclusion Criteria

I haven't had PSMA-radiotherapy in the last 12 months.

I haven't had any cancer except for certain skin cancers or superficial bladder cancer in the last 5 years.

I completed radiotherapy less than 8 weeks ago.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either darolutamide plus ADT or placebo plus ADT for a pre-specified duration of 24 months

24 months

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including health checks and cancer status assessments

Approximately 1 month

1 visit (in-person)

Treatment Details

Interventions

• ADT (Hormone Therapy)
• Darolutamide (Androgen Receptor Inhibitor)

Trial Overview The study compares the effectiveness of darolutamide combined with ADT versus placebo plus ADT in preventing cancer progression. Participants will take these treatments orally for 24 months and undergo regular health checks including blood tests and advanced imaging scans to monitor their condition.

Participant Groups

Group I: Darolutamide+ADT Experimental Treatment 2 Interventions

Participants will receive darolutamide plus ADT twice daily with food for a pre-specified duration of 24 months.

Group II: Placebo+ADT Placebo Group 2 Interventions

Participants will receive Placebo plus ADT twice daily with food for a pre-specified duration of 24 months.

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

🇪🇺 Approved in European Union as Androgen Deprivation Therapy for:

• Prostate Cancer

🇺🇸 Approved in United States as Androgen Deprivation Therapy for:

• Prostate Cancer

🇨🇦 Approved in Canada as Androgen Deprivation Therapy for:

• Prostate Cancer

🇯🇵 Approved in Japan as Androgen Deprivation Therapy for:

• Prostate Cancer

🇨🇳 Approved in China as Androgen Deprivation Therapy for:

• Prostate Cancer

🇨🇭 Approved in Switzerland as Androgen Deprivation Therapy for:

• Prostate Cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Alliance Urology Specialists Greensboro, NC

University of Texas Southwestern Medical Center-Harold C. Simmons Comprehensive Cancer Center Dallas, TX

Sir Mortimer B. Davis Jewish General Hospital - Radiation Oncology Montreal, Canada

Northwestern University Feinberg School of Medicine - Department of Urology Chicago, IL

More Trial Locations

Who Is Running the Clinical Trial?

Bayer Lead Sponsor

References

1. Canada pubmed.ncbi.nlm.nih.gov

Using darolutamide in advanced prostate cancer: How I Do It. [2021] Darolutamide is a nonsteroidal androgen inhibitor FDA approved for the treatment of castration-resistant non-metastatic prostate cancer (nmCRPC). After decades of offering androgen deprivation therapy (ADT) alone or first-generation androgen receptor blockers for patients whose PSA was rising despite castrate levels of testosterone, there are now three different treatment options to add to ADT. These include apalutamide approved in February 2018, enzalutamide FDA approved in June 2018, and darolutamide approved July 2019. Each of these androgen receptor pathway blockers, when added to ADT or surgical orchiectomy, prolongs metastasis-free-survival (MFS) and median survival (MS). This paper focuses on the use of the newest approved agent in this class, darololutmide.

2. United States pubmed.ncbi.nlm.nih.gov

Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. [2023] Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown.

3. France pubmed.ncbi.nlm.nih.gov

Darolutamide: A Review in Metastatic Hormone-Sensitive Prostate Cancer. [2023] Darolutamide (NUBEQA®) is an oral androgen receptor inhibitor (ARi) that is approved for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT) and docetaxel. In a pivotal trial, darolutamide plus ADT and docetaxel was superior to placebo plus ADT and docetaxel in prolonging the primary endpoint of overall survival, with improvements also reported in most secondary endpoints. Treatment with darolutamide plus ADT and docetaxel was associated with a manageable tolerability profile. Furthermore, the adverse events reported with darolutamide plus ADT and docetaxel were generally consistent with the safety profiles previously reported for ADT and docetaxel. Darolutamide expands the availability of treatment options in mHSPC and may be useful as a treatment for high-volume disease (typically defined as ≥ 4 bone metastases with spread outside of the pelvis and vertebral column).

4. New Zealand pubmed.ncbi.nlm.nih.gov

Darolutamide: First Approval. [2020] Darolutamide (NUBEQA™) is a structurally distinct non-steroidal androgen receptor antagonist being developed by Orion and Bayer as a treatment for prostate cancer. Based on positive results in the phase III ARAMIS trial, darolutamide was recently approved in the USA for the treatment of men with non-metastatic castration-resistant prostate cancer. This article summarizes the milestones in the development of darolutamide leading to this first approval.

5. United States pubmed.ncbi.nlm.nih.gov

Clinical Development of Darolutamide: A Novel Androgen Receptor Antagonist for the Treatment of Prostate Cancer. [2019] Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths among men. Androgen receptor (AR) signaling plays a key role in PC tumor growth and progression, with androgens stimulating PC proliferation and survival. Castration-resistant PC (CRPC) is characterized by increasing levels of prostate-specific antigen or radiographic progression despite androgen-deprivation therapy (ADT). In most patients, castration resistance results from aberrations in AR or the AR signaling pathway. Up to one-third of patients with localized high-risk PC will have disease progression on local therapy and develop CRPC. This review summarizes the key clinical data, including ongoing trials, for hormonal therapies in CRPC and provides an overview of the clinical development of darolutamide, a novel, nonsteroidal AR antagonist currently in phase III development for the treatment of nonmetastatic CRPC and metastatic hormone-sensitive PC. In phase I/II trials, darolutamide has demonstrated a favorable safety profile, antitumor activity, and significant decreases in prostate-specific antigen in patients with metastatic CRPC. In the phase III ARAMIS (NCT02200614; A Multinational, Randomized, Double-Blind, Placebo-Controlled, Phase III Efficacy and Safety Study of Darolutamide [ODM-201] in Men With High-Risk Non-metastatic Castration-Resistant Prostate Cancer) study, metastasis-free survival is being evaluated in men with nonmetastatic CRPC who will receive ADT in combination with darolutamide or placebo. The ARASENS (NCT02799602; A Randomized, Double-Blind, Placebo Controlled Phase III Study of Darolutamide [ODM-201] Versus Placebo in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Patients With Metastatic Hormone Sensitive Prostate Cancer) study is a placebo-controlled trial assessing whether the addition of darolutamide to ADT and docetaxel significantly prolongs overall survival in men with metastatic hormone-sensitive PC.

6. France pubmed.ncbi.nlm.nih.gov

Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. [2022] Oral darolutamide (Nubeqa™) is a novel second-generation, nonsteroidal, selective androgen receptor (AR) inhibitor indicated for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). In the pivotal multinational, phase 3 ARAMIS trial in men with nmCRPC, relative to placebo plus ongoing androgen deprivation therapy (ADT), darolutamide (+ ADT) significantly prolonged metastasis-free survival (MFS) at the time of the primary analysis and overall survival (OS) at the time of the final OS analysis and was generally well tolerated in extended follow-up. Albeit long-term data from the real-world setting are required to fully define the safety profile of darolutamide, current evidence from the final ARAMIS analysis indicates that darolutamide has a low propensity for CNS-related adverse events (AEs) associated with other currently approved second-generation AR inhibitors. Given the efficacy and safety evidence from the final ARAMIS analysis and the key role of second-generation AR inhibitors in the management of nmCRPC, darolutamide + ADT represents an important emerging option for the treatment of men with nmCRPC who are at high risk of developing metastatic prostate cancer.

7. Spain pubmed.ncbi.nlm.nih.gov

Darolutamide for treatment of castration-resistant prostate cancer. [2020] Darolutamide is a novel, nonsteroidal androgen receptor (AR)-signaling inhibitor. It serves as a second-generation antiandrogen and is currently indicated for the treatment of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). The product was approved by the United States Food and Drug Administration (FDA) in July 2019 and by the Japanese Ministry of Health, Labour and Welfare (MHLW) in January 2020 for the treatment of men with nmCRPC, and is awaiting approval in the E.U. for the same indication. This review will cover the background, preclinical development, safety, pharmacokinetics, pharmacodynamics and clinical studies that led to the approval of darolutamide. The key clinical data, ongoing trials and future directions for darolutamide are also discussed herein.

8. United States pubmed.ncbi.nlm.nih.gov

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. [2022] Darolutamide is a structurally unique androgen-receptor antagonist that is under development for the treatment of prostate cancer. We evaluated the efficacy of darolutamide for delaying metastasis and death in men with nonmetastatic, castration-resistant prostate cancer.