Lead-in phase: Darolutamide treatment for Biochemically Recurrent Prostate Cancer

Phase-Based Progress Estimates
Biochemically Recurrent Prostate CancerDarolutamide(BAY1841788, Nubeqa) - Drug
What conditions do you have?

Study Summary

Researchers are looking for a better way to treat men who have biochemically recurrent hormone-naïve prostate cancer. Hormone-naïve prostate cancer is a prostate cancer that has not yet been treated with hormonal therapy including androgen deprivation therapy (ADT). Biochemically recurrence (BCR) means that patients who received local treatment (surgery or radiation therapy) for prostate cancer now present with a rise in the blood level of a specific protein called PSA (prostate-specific antigen) but no detectable cancer or cancer spreading after a treatment that aimed to cure their prostate cancer (e.g. surgery and radiation). This may mean that the cancer has come back as the PSA level can be taken as a marker for prostate cancer development. Although men with BCR may not have symptoms for many years, proper treatment for BCR is important as the cancer may spread to other parts of the body in 7-8 years. In prostate cancer patients, male sex hormones like testosterone (also called androgens) can sometimes help the cancer spread and grow. To reduce androgen levels in these patients, androgen deprivation therapy (ADT) is often used. Second generation androgen receptor inhibitors including Darolutamide and Enzalutamide are available for the treatment of prostate cancer in addition to ADT. These inhibitors work by blocking androgen receptors and preventing it from attaching to proteins in cancer cells in the prostate. It is already known that men with prostate cancer benefit from these treatments. But besides benefits, Darolutamide and Enzalutamide are not without side effects. Clinical studies have shown that treatment with Enzalutamide increase testosterone level in serum, probably because it can pass blood brain barrier and goes into the central nervous system (CNS). The increased testosterone levels are thought to cause some specific side effects including so called feminizing side effects like overdevelopment of the breast tissue in men, and breast tenderness. Darolutamide has a distinct chemical structure and reduced ability to enter the CNS compared with Enzalutamide. That means that Darolutamide potentially leads to fewer and less severe side effects than Enzalutamide. In this study researchers will collect more data to learn to what extent Darolutamide affects serum testosterone levels in men with BCR in hormone-naïve prostate cancer. This study will consist of 2 stages. In stage 1 (also called lead-in phase) all participants will take Darolutamide by mouth twice a day. The study team will monitor and measure testosterone levels in the blood after: 12 weeks 24 weeks and 52 weeks of treatment. The second stage (also called randomized phase) is conditional and depends on the results from the stage 1. It will be conducted if after 24 weeks of treatment with Darolutamide in stage 1: a mean change in blood testosterone levels is below 45% and if the feminizing side effects (including overdevelopment of the breast tissue in men, and breast tenderness) will occur less frequently than previously reported. In the second stage of this study all participants will be randomly (by chance) assigned into two treatment groups, taking either Darolutamide twice daily or Enzalutamide once daily by mouth for a minimum of 12 and a maximum of 52 weeks. During both stages of this study the study team will: do physical examinations take blood and urine samples examine heart health using ECG examine heart and lung health using CPET check bone density using x-ray scan (DEXA) check vital signs check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and, if needed, bone scan ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments. The study participants who receive Darolutamide in stage 2 can continue to receive their treatments as long as they benefit from the treatment. The participants from the Enzalutamide group can also switch to treatment with Darolutamide after finishing stage 2. The study team will continue to check the participants' health and collect information about medical problems that might be related to Darolutamide until up to 30 days of last dose for those participants who continue on treatment with Darolutamide.

Eligible Conditions
  • Biochemically Recurrent Prostate Cancer

Treatment Effectiveness

Effectiveness Progress

1 of 3

Study Objectives

0 Primary · 14 Secondary · Reporting Duration: At week 4, 12, 24, 36, 52

Week 4
Body Weight Changes
Randomized Phase: Changes in the blood levels of Fat body mass and Lean body mass
Randomized Phase: Changes in the blood levels of Haemoglobin A1c
Body Weight Changes
Randomized Phase: Changes in the blood levels of dehydroepiandrosterone (DHEA), sex hormone-binding globulin (SHBG), Androstenedione and Prolactin
Body Weight Changes
Randomized Phase: Changes in the blood levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
Week 4
Lead-in phase: Serum Prostate-specific antigen (PSA)
Randomized Phase: Serum PSA
Week 24
Lead-in phase: Change in serum testosterone
Randomized Phase: Change in serum testosterone
Month 13
Lead-in phase: Number of participants with Adverse Event (AE)
Randomized Phase: Number of participants with Adverse Event (AE)
Randomized Phase: Quality of life (QoL) assessments

Trial Safety

Safety Progress

2 of 3
This is further along than 68% of similar trials

Trial Design

3 Treatment Groups

Randomized phase: Enzalutamide treatment
1 of 3
Lead-in phase: Darolutamide treatment
1 of 3
Randomized phase: Darolutamide treatment
1 of 3

Active Control

Experimental Treatment

65 Total Participants · 3 Treatment Groups

Primary Treatment: Lead-in phase: Darolutamide treatment · No Placebo Group · Phase 2

Lead-in phase: Darolutamide treatment
Experimental Group · 1 Intervention: Darolutamide(BAY1841788, Nubeqa) · Intervention Types: Drug
Randomized phase: Darolutamide treatment
Experimental Group · 1 Intervention: Darolutamide(BAY1841788, Nubeqa) · Intervention Types: Drug
Randomized phase: Enzalutamide treatment
ActiveComparator Group · 1 Intervention: Enzalutamide · Intervention Types: Drug

Trial Logistics

Trial Timeline

Screening: ~3 weeks
Treatment: Varies
Reporting: at week 4, 12, 24, 36, 52

Who is running the clinical trial?

BayerLead Sponsor
2,151 Previous Clinical Trials
23,875,082 Total Patients Enrolled

Eligibility Criteria

Age 18+ · Male Participants · 10 Total Inclusion Criteria

Mark “Yes” if the following statements are true for you:
You have had a prostatectomy or definitive radiotherapy for prostate cancer.
Patients must have a PSA rise ≥2 ng/ml at screening.
You have had a rising PSA for at least 3 consecutive PSA values, AND the interval between your first and last PSA values is >8 weeks but <12 months.
You have an ECOG score of 0 - 1.
You are male and ≥ 18 years of age.
You have a baseline serum testosterone level of 150 ng/dl or higher.
Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate.
You have 5 or less asymptomatic metastatic lesions on conventional or PSMA-PET based imaging methods permitted