A Study Called ARAMON to Learn to What Extent Does Study Treatment With Darolutamide Affects Testosterone Levels in Men With Prostate Cancer That Had Not Been Treated With Hormonal Therapy Compared to Treatment With Enzalutamide
- Conditions
- Biochemically Recurrent Prostate Cancer
- Interventions
- Drug: Darolutamide(BAY1841788, Nubeqa)
- Registration Number
- NCT05526248
- Lead Sponsor
- Bayer
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 65
- Male of ≥ 18 years of age.
- Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate.
- Prior treatment with primary radical prostatectomy or definitive RT for localized prostate cancer
- Patients must have PSA ≥0.2 ng/mL after ART or SRT post-RP or after RP in participants who are unfit for ART or SRT, OR PSA ≥2 ng/mL above the nadir after primary RT only. (RP, radical prostatectomy; ART, adjuvant radiotherapy; SRT, salvage radiotherapy; RT primary radiotherapy)
- The presence of < 5 asymptomatic metastatic lesions on conventional or PSMA-PET based imaging methods permitted. Lesions that need treatment with any opioid based analgetic are considered symptomatic
- PSADT ≤ 20 months calculated per PCWG3 + RECIST 1.1 per Scher et al. (Scher et al. 2016) and MSKCC nomogram.
- Eastern Cooperative Oncology Group ECOG (PS) of 0 - 1.
- Serum testosterone >150 ng/dl.
- Patients must have adequate organ function within 4 weeks before the first dose of study intervention.
- More than 30 days (or 5 half-lives) (whichever is longer) since prior participation in another clinical trial with an investigational medicinal product.
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Prior treatment with ADT of up to 6 months for localized disease is permitted but not if during the prior 6 months before first dose of study intervention. Plan to initiate ADT during the trial period is not allowed.
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Radiation therapy or major surgery within 4 weeks of screening.
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Systemic glucocorticoids within 3 months prior to the first dose or study intervention was expected to require systemic glucocorticoids during the study period
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Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV)
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Uncontrolled hypertension
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A gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study intervention.
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Prior history of a clinically significant malignancy with the exception of basal cell, squamous cell carcinoma of the skin, and superficial bladder cancer.
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Prior treatment with:
- Second-generation androgen receptor (AR) inhibitors such as enzalutamide, apalutamide, darolutamide other investigational AR inhibitors
- or Cytochrome P17 enzyme inhibitor such as abiraterone acetate as antineoplastic treatment for prostate cancer
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Prior history of gynecomastia
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Use of herbal products that may have had hormonal anti-prostate cancer activity or were known to decrease PSA levels (e.g., saw palmetto) within 4 weeks before the first dose of study intervention
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lead-in phase: Darolutamide treatment Darolutamide(BAY1841788, Nubeqa) Darolutamide treatment arm is single cohort in lead-in phase. Randomized phase: Darolutamide treatment Darolutamide(BAY1841788, Nubeqa) The conduct of the randomized phase is dependent on the results of the lead-in phase. Randomized phase: Enzalutamide treatment Enzalutamide The conduct of the randomized phase is dependent on the results of the lead-in phase.
- Primary Outcome Measures
Name Time Method Randomized Phase: Change in serum testosterone From baseline to week 12 Lead-in phase: Change in serum testosterone From baseline to week 12
- Secondary Outcome Measures
Name Time Method Lead-in phase: Number of participants with Adverse Event (AE) From the signing of Informed Consent Form (ICF) up to 30 days after last dose administration, up to 13 months AE assessments using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0
Randomized Phase: Change in serum testosterone From baseline to week 24 and 52 Randomized Phase: Serum PSA At week 4, 12, 24, 36, 52 Randomized Phase: Number of participants with Adverse Event (AE) From the signing of Informed Consent Form (ICF) up to 30 days after last dose administration, up to 13 months AE assessments using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0
Randomized Phase: Quality of life (QoL) assessments From the signing of Informed Consent Form (ICF) up to 30 days after last dose administration, up to 13 months QoL assessment using Functional Assessment of Cancer Therapy - Prostate Cancer (FACT-P) questionnaire. FACT-P is a multidimension, selfreport QoL instrument specifically designed for patients with prostate cancer. It consists of 39 questions items, made up by 2 parts: the 27 questions for functional assessment of cancer therapy general (FACT-G) and 12 prostate cancer subscale questions. It assesses 4 main domains which are: physical (n=7), social/family (n=7), emotional (n=6) and functional wellbeing (n=7).
Randomized Phase: Changes in the blood levels of dehydroepiandrosterone (DHEA), sex hormone-binding globulin (SHBG), Androstenedione and Prolactin At week 4, 12, 24, 36 and 52 Randomized Phase: Changes in the blood levels of Estradiol At week 4, 12, 24, 36 and 52 Randomized Phase: Changes in the blood levels of Fat body mass and Lean body mass At week 4, 12, 24, 36 and 52 Lead-in phase: Change in serum testosterone From baseline to week 24 and 52 Lead-in phase: Serum Prostate-specific antigen (PSA) At week 4, 12, 24, 36, 52 Randomized Phase: Changes in the blood levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) At week 4, 12, 24, 36 and 52 Randomized Phase: Changes in the blood levels of Total cholesterol, High-density and low-density lipoproteins, Triglycerides and Fasting glucose At week 4, 12, 24, 36 and 52 Randomized Phase: Changes in the blood levels of Haemoglobin A1c At week 4, 12, 24, 36 and 52 Randomized Phase: Changes in the blood levels of dihydrotestosterone (DHT) At week 4, 12, 24, 36 and 52
Trial Locations
- Locations (5)
Memorial Sloan Kettering Cancer Center New York - Main Campus
🇺🇸New York, New York, United States
Unio Specialty Care - Urology - Sherman Oaks
🇺🇸Sherman Oaks, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center - Oncology
🇺🇸Boston, Massachusetts, United States
Central Ohio Urology Group - Gahanna
🇺🇸Gahanna, Ohio, United States