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 (ARAMON)

A 2-stage, Lead-in and Randomized, Phase 2, Open-label Study of Darolutamide Versus Enzalutamide as Monotherapy on Testosterone Levels Change in Men With Hormone-Naïve Prostate Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Biochemically Recurrent Prostate Cancer
• Intervention / Treatment: Drug: Darolutamide(BAY1841788, Nubeqa); Drug: Enzalutamide

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bayer Clinical Trials Contact; Phone Number: (+)1-888-84 22937; Email: clinical-trials-contact@bayer.com

Study Locations

• United States
  • California
    • Sherman Oaks, California, United States, 91411
      • Not yet recruiting
      • Genesis Research LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-2696
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Not yet recruiting
      • Beth Israel Deaconess Medical Center - Boston
  • New York
    • New York, New York, United States, 10021-0005
      • Not yet recruiting
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43214-2416
      • Not yet recruiting
      • Central Ohio Urology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Radiation therapy or major surgery within 4 weeks of screening.
• Systemic glucocorticoids within 3 months prior to the first dose or study intervention was expected to require systemic glucocorticoids during the study period
• 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)
• Uncontrolled hypertension
• A gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study intervention.
• Prior history of a clinically significant malignancy with the exception of basal cell, squamous cell carcinoma of the skin, and superficial bladder cancer.

• 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
• Prior history of gynecomastia
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lead-in phase: Darolutamide treatment; Darolutamide treatment arm is single cohort in lead-in phase.	Drug: Darolutamide(BAY1841788, Nubeqa); tablet, oral
Experimental: Randomized phase: Darolutamide treatment; The conduct of the randomized phase is dependent on the results of the lead-in phase.	Drug: Darolutamide(BAY1841788, Nubeqa); tablet, oral
Active Comparator: Randomized phase: Enzalutamide treatment; The conduct of the randomized phase is dependent on the results of the lead-in phase.	Drug: Enzalutamide; tablet, oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Lead-in phase: Change in serum testosterone	From baseline to week 12
Randomized Phase: Change in serum testosterone	From baseline to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Lead-in phase: Number of participants with Adverse Event (AE)	AE assessments using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0	From the signing of Informed Consent Form (ICF) up to 30 days after last dose administration, up to 13 months
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)	AE assessments using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0	From the signing of Informed Consent Form (ICF) up to 30 days after last dose administration, up to 13 months
Randomized Phase: Quality of life (QoL) assessments	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).	From the signing of Informed Consent Form (ICF) up to 30 days after last dose administration, up to 13 months
Randomized Phase: Changes in the blood levels of dihydrotestosterone (DHT)		At week 4, 12, 24, 36 and 52
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 luteinizing hormone (LH) and follicle-stimulating hormone (FSH)		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 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 Fat body mass and Lean body mass		At week 4, 12, 24, 36 and 52

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2022
• Primary Completion (Estimated): August 19, 2025
• Study Completion (Estimated): May 28, 2026

Study Registration Dates

• First Submitted: August 31, 2022
• First Submitted That Met QC Criteria: August 31, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Hormone-naive prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 21953

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No