A Dose Optimization Study of Enzalutamide in Elderly Patients With Advanced Prostate Cancer

This is a phase II, single-centre, pragmatic, non-randomized, dose escalation study to evaluate optimal dose levels of enzalutamide in elderly patients using pharmacokinetic blood sampling concentrations.

Study Overview

• Status: Not yet recruiting
• Conditions: Elderly Patients; Pharmacokinetic Study; Prostate Cancer Patients
• Intervention / Treatment: Drug: Enzalutamide Dose Escalation; Drug: Standard of Care

Detailed Description

Enzalutamide is an androgen receptor pathway inhibitor (ARPI) drug that is commonly used in prostate cancer. It is safe, effective, and is generally well tolerated by patients at the standard dose of 160mg, however researchers have seen that it may cause unfavorable side effects in elderly patients 75 and older such as fatigue and cognitive impairment that impact their quality of life more significantly than those under 75.

To date there is limited research comparing differences in side effects and quality of life experienced by elderly patients on standard versus a lower dose of enzalutamide. Dose reductions are common, particularly in elderly patients, although they are not explicitly recommended on the drug label, and as a result this study seeks to build on the existing research and practice experience to evaluate how enzalutamide is metabolized in elderly patients and whether this difference warrants different dosing standards in these patients.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Daniel Khalaf, MD; Phone Number: 416-480-4617; Email: daniel.khalaf@sunnybrook.ca
• Study Contact Backup: Name: Elyse Watkins; Email: elyse.watkins@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
      • Contact: Daniel Khalaf, MD; Phone Number: 416-480-4617; Email: daniel.khalaf@sunnybrook.ca
      • Principal Investigator: Daniel Khalaf, MD
      • Sub-Investigator: Urban Emmenegger, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Main Cohort:

1. Male aged 75 years or older.
2. Signed Informed Consent Form

3. Advanced prostate cancer with a Health Canada approved indication for enzalutamide amongst the following:

   1. High-risk biochemical recurrent hormone sensitive prostate cancer (high risk definition: PSA doubling time of ≤9 months and a PSA level of ≥2 ng per milliliter above nadir after radiation therapy or ≥1 ng per milliliter after radical prostatectomy with or without postoperative radiation therapy).
   2. Metastatic castration-sensitive prostate cancer.
   3. Non-metastatic castration-resistant prostate cancer (M0CRPC) with a PSA doubling time of ≤9 months
4. Participants must receive concomitant androgen deprivation therapy with either a Luteinizing hormone-releasing hormone (LHRH) antagonist or agonist, or have had bilateral orchiectomy.

5. Participant is capable, in the opinion of the investigator, of completing all study assessments and procedures, including blood draws for PK sampling according to the required schedule as per the study protocol as well as PROs.

   1. Note, for patients who speak a language other than English, PROs may be completed with the help of an interpreter, or translated PROs may be substituted, if available in the patient's primary language.

Control Cohort:

1. Age < 70 years
2. Receiving enzalutamide for advanced prostate, for any indication as per Product Monograph
3. Receiving the same dose of enzalutamide taken daily and fully compliant for ≥ 29 days
4. Signed Informed Consent Form

Exclusion Criteria:

Main Cohort:

1. Metastatic castration-resistant prostate cancer
2. Pain related to bone metastasis requiring the use of opioid analgesics
3. Impending spinal cord compression related to metastasis to vertebral column
4. Painful femoral neck or any other metastasis judged to be at risk of short-term pathological fracture in the investigator's opinion
5. Co-administration of medications which are moderate to strong CYP2C8 inducers or inhibitors
6. Co-administration of medications which are moderate to strong CYP3A4 inducers or inhibitors
7. History of seizure disorder
8. History of moderate-severe dementia
9. Performance status > ECOG 2
10. Uncontrolled hypertension (defined as sustained systolic blood pressure above 160 and/or diastolic above 100 despite the adequate use of antihypertensive medication)
11. Participants with a known history of dementia, seizure disorder, intracranial lesions, moderate to severe hepatic impairment, stage ≥ 3 chronic renal failure or stroke will also be excluded

Control Cohort:

1. Unable to provide written informed consent
2. Receiving a medication which is a moderate-strong CYP2C8 or CYP3A4 inducer or inhibitor

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Main Cohort; Participants 75 years and older who have have a confirmed diagnosis of advanced prostate cancer, and are suitable candidates to receive enzalutamide but have not started treatment with the drug yet.	Drug: Enzalutamide Dose Escalation; Participants will be allocated to receive one of 4 dose levels of enzalutamide; Level 1: 40mg; Level 2: 80mg; Level 3: 120mg; Level 4: 160mg There will be 4 participants per dose level. After 8 weeks of treatment at the initial dose level, the study doctor will review treatment progress and may escalate to a higher dose level at their discretion. For each dose level participants move up to (if applicable), they will repeat this same 8 weeks of treatment and evaluation process.
Active Comparator: Control Cohort; The control cohort will enroll participants that are under 70 years old, and are currently receiving enzalutamide for a period of more than 29 days.	Drug: Standard of Care; Participants will continue to receive enzalutamide per standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enzalutamide Plasma Levels	To compare enzalutamide plasma concentrations in patients ≥ 75 years of age with younger patients at various dose levels.	At day 29 and 57 of all applicable dose levels, up to 32 weeks maximum (4 levels, 8 weeks apart)

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Investigators: Principal Investigator: Daniel Khalaf, MD, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: March 25, 2026
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: prostate cancer; enzalutamide; elderly patients
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: 6986 (South African Clinical Trials Registry (SANCTR))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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