ODM-201 in Addition to Standard ADT and Docetaxel in Metastatic Castration Sensitive Prostate Cancer (ARASENS)

• ClinicalTrials.gov Identifier: NCT02799602
• Recruitment Status: Active, not recruiting
• First Posted: June 15, 2016
• Last Update Posted: September 29, 2022
• Sponsor: Bayer
• Collaborator: Orion Corporation, Orion Pharma
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: June 6, 2016
• First Posted Date: June 15, 2016
• Last Update Posted Date: September 29, 2022
• Actual Study Start Date: November 30, 2016
• Actual Primary Completion Date: October 25, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 10, 2016)

Overall survival [ Time Frame: approximately 70 months ]

From date of randomization until death from any cause, during treatment and during active and long term follow-up

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 27, 2018)

• Time to castration resistant prostate cancer [ Time Frame: approximately 70 months ]
  Approximately every 12 weeks (according to standards of care) up to the time of PSA progression by soft tissue/visceral lesions or progression by bone lesions, whatever come first.
• Time to initiation of subsequent antineoplastic therapy [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the date of first subsequent antineoplastic therapy for prostate cancer.
• Symptomatic skeletal event free survival (SSE-FS) [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the first occurrence of SSE or death from any cause, whatever comes first SSE is defined as external beam radiation therapy (EBRT) to relieve skeletal symptoms, or new symptomatic pathologic bone fracture, or occurrence of spinal cord compression or tumor-related orthopedic surgical intervention, whichever comes first.
• Time to first symptomatic skeletal event (SSE) [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the first occurrence of SSE. SSE is defined as EBRT to relieve skeletal symptoms, or new symptomatic pathologic bone fracture, or occurrence of spinal cord compression or tumor-related orthopedic surgical intervention, whichever comes first.
• Time to initiation of opioid use [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the opiod use.
• Time to pain progression [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the first date a subject experiences a pain progression. Pain to be assessed with a patient reported questionaire.
• Time to worsening of physical symptoms of disease [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the first date a subject experiences an increase in physical symptoms. Physical symptoms of disease to be assessed with a patient reported questionaire.
• Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: approximately 70 months ]

Original Secondary Outcome Measures (submitted: June 10, 2016)

• Time to castration resistant prostate cancer [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the time of PSA progression or progression by soft tissue lesions or progression by bone lesions, whatever comes first.
• Time to initiation of subsequent antineoplastic therapy [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the date of first subsequent antineoplastic therapy for prostate cancer.
• Symptomatic skeletal event free survival (SSE-FS) [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the first occurrence of SSE or death from any cause, whatever comes first SSE is defined as external beam radiation therapy (EBRT) to relieve skeletal symptoms, or new symptomatic pathologic bone fracture, or occurrence of spinal cord compression or tumor-related orthopedic surgical intervention, whichever comes first.
• Time to first symptomatic skeletal event (SSE) [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the first occurrence of SSE. SSE is defined as EBRT to relieve skeletal symptoms, or new symptomatic pathologic bone fracture, or occurrence of spinal cord compression or tumor-related orthopedic surgical intervention, whichever comes first.
• Time to initiation of opioid use [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the opiod use.
• Time to pain progression [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the first date a subject experiences a pain progression. Pain to be assessed with a patient reported questionaire.
• Time to worsening of physical symptoms of disease [ Time Frame: approximately 70 months ]
  Every 12 weeks up to the first date a subject experiences an increase in physical symptoms. Physical symptoms of disease to be assessed with a patient reported questionaire.
• Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: approximately 70 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ODM-201 in Addition to Standard ADT and Docetaxel in Metastatic Castration Sensitive Prostate Cancer
• Official Title: 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
• Brief Summary: The purpose of the study is to assess the efficacy and safety of BAY1841788 (darolutamide (ODM-201)) in combination with standard androgen deprivation therapy (ADT) and docetaxel in patients with metastatic hormone sensitive prostate cancer.

Detailed Description

This is a randomized, double-blind, placebo-controlled, multicenter phase III study. The study population will consist of approximately 1300 subjects with metastatic hormone sensitive prostate cancer (mHSPC), who will be randomized (1:1 ratio) to receive 600 mg (2 x 300 mg tablets) of darolutamide (ODM-201)/placebo twice daily with food, equivalent to a total daily dose of 1200 mg, in addition to standard androgen deprivation therapy (ADT) and docetaxel. Subjects will be stratified at randomization for the extent of disease and for Alkaline Phosphatase levels. All subjects will be treated with ADT as standard therapy. Six cycles of docetaxel will be administered after randomization.

The subjects considered for inclusion in the study will have metastatic prostate cancer and will be candidates for ADT and docetaxel.

Treatment with darolutamide (ODM-201)/placebo will be administered until symptomatic progressive disease, change of antineoplastic therapy, unacceptable toxicity, until subject withdraws consent, withdrawal from the study at the discretion of the investigator or his/her designated associate(s), death, non-compliance, or if sponsor terminates the study.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Metastatic Hormone-sensitive Prostate Cancer

Intervention

• Drug: BAY1841788 / darolutamide (ODM-201)
  600mg (2 tablets of 300 mg) of darolutamide (ODM-201)/placebo twice daily with food, equivalent to a total a daily dose of 1200 mg in addition to standard ADT (luteinizing hormone releasing hormone (LHRH) agonist/antagonist or orchiectomy) and 6 cycles of docetaxel
• Drug: Standard ADT (androgen deprivation therapy)
  As prescribed by the treating physician.
• Drug: Docetaxel
  As prescribed by the treating physician.
• Drug: Placebo
  Placebo matching darolutamide (ODM-201) tablets in appearance, bid orally with food, in addition to standard ADT (luteinizing hormone releasing hormone [LHRH] agonist/antagonist or orchiectomy) and 6 cycles of docetaxel.

Study Arms

• Experimental: BAY1841788 /darolutamide (ODM-201)+standard ADT+Docetaxel
  Co-administration of BAY 1841788 / darolutamide (ODM-201), standard ADT and docetaxel
  Interventions:

  • Drug: BAY1841788 / darolutamide (ODM-201)
  • Drug: Standard ADT (androgen deprivation therapy)
  • Drug: Docetaxel
• Placebo Comparator: Placebo + standard ADT + Docetaxel
  Co-administration of Placebo matching BAY 1841788 / darolutamide (ODM-201) tablets, standard ADT and docetaxel
  Interventions:

  • Drug: Standard ADT (androgen deprivation therapy)
  • Drug: Docetaxel
  • Drug: Placebo

Publications *

• Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford D, Manarite J, Muslin D, Farrington T, Tombal B. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer: a patient and caregiver perspective and plain language summary of the ARASENS trial. Future Oncol. 2022 Jul;18(21):2585-2597. doi: 10.2217/fon-2022-0433. Epub 2022 Jun 3.
• Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, Kopyltsov E, Park CH, Alekseev B, Montesa-Pino A, Ye D, Parnis F, Cruz F, Tammela TLJ, Suzuki H, Utriainen T, Fu C, Uemura M, Mendez-Vidal MJ, Maughan BL, Joensuu H, Thiele S, Li R, Kuss I, Tombal B; ARASENS Trial Investigators. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142. doi: 10.1056/NEJMoa2119115. Epub 2022 Feb 17.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 20, 2018): 1303
• Original Estimated Enrollment (submitted: June 10, 2016): 1300
• Estimated Study Completion Date: June 30, 2023
• Actual Primary Completion Date: October 25, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of prostate.
• Metastatic disease
• Candidates for ADT and docetaxel.
• Started ADT with or without first generation anti androgen, but no longer than 12 weeks before randomization
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate bone marrow, liver and renal function

Exclusion Criteria:

• Prior treatment with: LHRH agonist/antagonists; second generation androgen receptor (AR) inhibitors such as enzalutamide, ARN-509, darolutamide (ODM-201), other investigational AR inhibitors; CYP17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as antineoplastic treatment for prostate cancer; chemotherapy or immunotherapy for prostate cancer prior to randomization.
• Treatment with radiotherapy/radiopharmaceuticals within 2 weeks before randomization.
• 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)
• Had a prior malignancy. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e., pTis, pTa, and pT1) is allowed, as well as any other cancer for which treatment has been completed 5 years before randomization and from which the subject has been disease-free
• Gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study treatment.
• Inability to swallow oral medications

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Finland, France, Germany, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, Spain, Sweden, Taiwan, United Kingdom, United States
• Removed Location Countries: Czech Republic, Switzerland

Administrative Information

• NCT Number: NCT02799602
• Other Study ID Numbers: 17777; 2015-002590-38 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bayer
• Original Responsible Party: Same as current
• Current Study Sponsor: Bayer
• Original Study Sponsor: Same as current
• Collaborators: Orion Corporation, Orion Pharma

Investigators

• Study Director: Bayer Study Director; Bayer

• PRS Account: Bayer
• Verification Date: September 2022