Darolutamide in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer

Metastatic Hormone-sensitive Prostate Cancer Clinical Trial

— ARASENS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02799602
• Other study ID #: 17777
• Secondary ID: 2015-002590-38
• Status: Completed
• Phase: Phase 3
• Start date: November 30, 2016
• Est. completion date: April 11, 2023

Study information

• Verified date: March 2024
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1306
• Est. completion date: April 11, 2023
• Est. primary completion date: October 25, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypersensitivity
• Metastatic Hormone-sensitive Prostate Cancer
• Prostatic Neoplasms

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
• Standard ADT (androgen deprivation therapy)
As prescribed by the treating physician.
• Docetaxel
As prescribed by the treating physician.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Orion Corporation, Orion Pharma

Countries where clinical trial is conducted

United States,  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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OS From Date of Randomization Until Death From Any Cause - Number of Events	Overall survival (OS) was defined as the time from the date of randomization until death from any cause.; Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.; Long-term (Survival) follow-up period: After Active follow-up, patients continued to be contacted approximately every 12 weeks by phone. The end of the Survival follow-up period was defined as when the patient died, was lost to follow-up, withdrew consent, or at the end-of-study.	From randomization of the first participant until death from any cause up to 25 OCT 2021 cut-off date 533 OS events were reached (approximate 59 months)
Primary	OS From Date of Randomization Until Death From Any Cause - Month	Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.; Long-term (Survival) follow-up period: After Active follow-up, patients continued to be contacted approximately every 12 weeks by phone. The end of the Survival follow-up period was defined as when the patient died, was lost to follow-up, withdrew consent, or at the end-of-study.; Median, percentile and other 95% CIs were computed using Kaplan-Meier estimates.; NA = Value cannot be estimated due to censored data	From randomization of the first participant until death from any cause up to 25 OCT 2021 cut-off date 533 OS events were reached (approximate 59 months)
Secondary	Number of Participants With TEAEs	TEAEs = Treatment-emergent adverse events, were defined as any event(s) arising or worsening after the first dose of darolutamide or placebo, until 30 days after the last dose of darolutamide or placebo administration.	From the first dose of darolutamide or placebo until 30 days after the last dose of darolutamide or placebo administration up to cut-off date for the final completion analysis 11 APR 2023 (approximately 77 months)
Secondary	Time to Castration-Resistant Prostate Cancer (CRPC) - Number of Events	Time to castration-resistant prostate cancer was defined as the time from randomization to the first occurrence of one of the following events: PSA progression, Radiological progression by bone lesions, or Radiological progression by soft tissue and visceral lesions.; Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first occurrence of an CRPC event up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Time to Castration-Resistant Prostate Cancer (CRPC) - Month	Time to castration-resistant prostate cancer was defined as the time from randomization to the first occurrence of one of the following events: PSA progression, Radiological progression by bone lesions, or Radiological progression by soft tissue and visceral lesions.; Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.; NA = Value cannot be estimated due to censored data	From randomization of the first participant to the first occurrence of an CRPC event up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Time to Pain Progression - Number of Events	Time to pain progression was defined as the time from randomization to the first date a patient experienced pain progression.; Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first occurrence of a pain progression event up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Time to Pain Progression - Month	Time to pain progression was defined as the time from randomization to the first date a patient experienced pain progression.; Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.; NA = Value cannot be estimated due to censored data	From randomization of the first participant to the first occurrence of a pain progression event up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Symptomatic Skeletal Event Free Survival (SSE-FS) - Number of Events	Symptomatic skeletal event-free survival (SSE-FS) was defined as the time from randomization to the first occurrence of an SSE or death from any cause, whichever occurred first.; Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first occurrence of an SSE event or death from any cause, whichever occurred first up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Symptomatic Skeletal Event Free Survival (SSE-FS) - Month	Symptomatic skeletal event-free survival (SSE-FS) was defined as the time from randomization to the first occurrence of an SSE or death from any cause, whichever occurred first.; Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.; NA = Value cannot be estimated due to censored data	From randomization of the first participant to the first occurrence of an SSE event or death from any cause, whichever occurred first up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Time to First Symptomatic Skeletal Event (SSE) - Number of Events	Time to the first SSE was defined as the time from randomization to the first occurrence of an SSE. Identical to the definition used for SSE-FS. Death was not considered as an event in this endpoint.; Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first occurrence of an SSE event up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Time to First Symptomatic Skeletal Event (SSE) - Month	Time to the first SSE was defined as the time from randomization to the first occurrence of an SSE. Identical to the definition used for SSE-FS. Death was not considered as an event in this endpoint.; Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.; NA = Value cannot be estimated due to censored data	From randomization of the first participant to the first occurrence of an SSE event up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Time to Initiation of Subsequent Antineoplastic Therapy - Number of Events	Time to initiation of subsequent systemic antineoplastic therapy was defined as the time from randomization to the initiation of first subsequent systemic antineoplastic therapy.; Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the initiation of first subsequent systemic antineoplastic therapy up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Time to Initiation of Subsequent Antineoplastic Therapy - Month	Time to initiation of subsequent systemic antineoplastic therapy was defined as the time from randomization to the initiation of first subsequent systemic antineoplastic therapy.; Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.; NA = Value cannot be estimated due to censored data	From randomization of the first participant to the initiation of first subsequent systemic antineoplastic therapy up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Time to Worsening of Disease-Related Physical Symptoms - Number of Events	Time to worsening of disease-related physical symptoms was defined as the time from randomization to the first date a patient experienced an increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire.; Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Time to Worsening of Disease-Related Physical Symptoms - Month	Time to worsening of disease-related physical symptoms was defined as the time from randomization to the first date a patient experienced an increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire.; Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Time to Initiation of Opioid Use for =7 Consecutive Days - Number of Events	Time to the initiation of opioid use for =7 consecutive days was defined as the time from randomization to the date of the first opioid use for =7 consecutive days. Data of opioid use related to cancer pain was included in the analysis, and opioid use for non-malignant causes was excluded.; Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first opioid use for =7 consecutive days up to 25 OCT 2021 cut-off date approximately 59 months
Secondary	Time to Initiation of Opioid Use for =7 Consecutive Days - Month	Time to the initiation of opioid use for =7 consecutive days was defined as the time from randomization to the date of the first opioid use for =7 consecutive days. Data of opioid use related to cancer pain was included in the analysis, and opioid use for non-malignant causes was excluded.; Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.; Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.; NA = Value cannot be estimated due to censored data	From randomization of the first participant to the first opioid use for =7 consecutive days up to 25 OCT 2021 cut-off date approximately 59 months

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