Duration of Androgen Receptor Pathway Inhibitor and ADT With Metastasis Directed Therapy in Oligometastatic Cancer of the Prostate (DIRECT) (DIRECT)

Duration of Androgen Receptor Pathway Inhibitor and ADT With Metastasis Directed Therapy in Oligometastatic Cancer of the Prostate

This is a multi-centre, investigator-initiated, three-arm, randomized trial to investigate the addition on androgen receptor pathway inhibitor and atorvastatin to standard of care radiation and hormone therapy improve quality of life.

Participants will either receive standard of care radiation and hormone (ADT) therapy (Arm 1), standard of care radiation and hormone (ADT) therapy plus oral abiraterone for 8-9 months (Arm 3) or standard of care radiation and hormone (ADT) therapy plus oral abiraterone for 8-9 months plus atorvastatin for 2 years (Arm 4). Participants will be routinely follow-up in clinic or remotely for up to 5 years.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Prostate Cancer
• Intervention / Treatment: Other: Standard of Care SBRT and ADT; Drug: Abiraterone; Drug: Atorvastatin

• Study Type: Interventional
• Enrollment (Estimated): 352
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rachel Glicksman, MD; Phone Number: 416-946-4961; Email: rachel.glicksman@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Center
      • Contact: Rachel Glicksman, MD; Phone Number: 4483 416-946-4501; Email: rachel.glicksman@uhn.ca
  • Ontartio
    • Toronto, Ontartio, Canada, M4N 3M5
      • Active, not recruiting
      • Sunnybrook Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age > 18 years
2. Able to provide informed consent
3. Histologic diagnosis of prostate adenocarcinoma
4. ECOG performance status 0-2

5. Stage IV castrate sensitive metachronous metastatic prostate cancer. diagnosed within 6 months of study enrollment with 1-10 metastases

   1. Maximum one metastatic deposit on conventional imaging (CT or bone scan or MR)
   2. Additional metastases can be detectable by PSMA PET only
6. All sites of disease are amenable to and can be safely treated with radiotherapy
7. Patients decline continuous use of ADT

Exclusion Criteria (for all patients):

1. Significant comorbidities rendering patient not suitable for ADT, ARPI (enzalutamide or abiraterone) and SBRT

   a. Patients with significant comorbidities rendering patient not suitable for atorvastatin is not an exclusion criteria, as these patients can still enroll and be randomized between Arms 1 and 3.

2. History of malignancy within the past 5 years, excluding non-melanoma skin cancer and in-situ cancer, managed non-curatively
3. Prior use of salvage systemic therapy
4. Evidence of spinal cord compression

Exclusion Criteria (for Arm 4 only, after randomization)

1. ALT/AST > 3 x ULN
2. History of myasthenia gravis or active myasthenia gravis
3. History of ocular myasthenia or active ocular myasthenia

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
Other: Arm 1 - Standard of Care; Participants in this group will receive standard of care radiation treatment and ADT. Participants will start ADT first. Androgen deprivation therapy will be delivered via injection every 3-4 months as per standard of care (for 8-9 months total). At the same time, or within 3 months of starting ADT, participants will begin radiation treatment. The radiation treatment course will consist of 2-5 sessions of radiation daily or every other day (the number of sessions will be determined by the physician depending on the location of cancer, number of cancer spots, etc.).	Other: Standard of Care SBRT and ADT; Standard of care stereotactic body radiation therapy (SBRT) and androgen deprivation therapy (ADT)
Experimental: Arm 3 - Study Treatment (Abiraterone); Participants in this group will receive standard of care radiation treatment and ADT, plus abiraterone. Participants will start ADT first. Androgen deprivation therapy will be delivered via injection every 3-4 months as per standard of care (for 8-9 months total). At the same time, or within 3 months of starting ADT, participants will begin radiation treatment. The radiation treatment course will consist of 2-5 sessions of radiation daily or every other day (the number of sessions will be determined by the physician depending on the location of cancer, number of cancer spots, etc.). In addition, participants will take abiraterone orally (by mouth) daily for 8-9 months. Participants will start the first pill within a month of enrollment. This pill can be taken around the same time of day with or without food.	Other: Standard of Care SBRT and ADT; Standard of care stereotactic body radiation therapy (SBRT) and androgen deprivation therapy (ADT); Drug: Abiraterone; Second-generation androgen pathway inhibitor (ARAT), oral tablet
Experimental: Arm 4: Study Treatment (Abiraterone + Atorvastatin); Participants in this group will receive standard of care radiation treatment and ADT, plus abiraterone and atorvastatin. Participants will start ADT first. Androgen deprivation therapy will be delivered via injection every 3 or 4 months as per standard of care (for 8-9 months total). At the same time, or within 3 months of starting ADT, participants will begin radiation treatment. The radiation treatment course will consist of 2-5 sessions of radiation daily or every other day (the number of sessions will be determined by the physician depending on the location of cancer, number of cancer spots, etc.). In addition, participants will take abiraterone orally (by mouth) daily for 8-9 months. Participants will start the first pill within a month of enrollment. This pill can be taken around the same time of day with or without food. Participants will also take atorvastatin once daily by mouth for 2 years. This may also be taken with or without food.	Other: Standard of Care SBRT and ADT; Standard of care stereotactic body radiation therapy (SBRT) and androgen deprivation therapy (ADT); Drug: Abiraterone; Second-generation androgen pathway inhibitor (ARAT), oral tablet; Drug: Atorvastatin; Lipid metabolism regulator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Determine if progression free survival improves with the addition of short-term ARPI (abiraterone or abiraterone) with or without statin (atorvastatin) to standard of care treatment.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported quality of life	Determine if the addition of short-term ARPI (abiraterone or enzalutamide) with or without statin (atorvastatin) to standard of care treatment results in a patient-reported quality of life difference compared to standard of care treatment alone using quality of life questionnaires (FACT-P).	5 years
Patient-reported quality of life	Determine if the addition of short-term ARPI (abiraterone or enzalutamide) with or without statin (atorvastatin) to standard of care treatment results in a patient-reported quality of life difference compared to standard of care treatment alone using quality of life questionnaires (FACT-Fatigue).	5 years
Physician-reported toxicity	Determine if the addition of short-term ARPI (abiraterone or enzalutamide) with or without statin (atorvastatin) to standard of care treatment results in a physician-reported difference in acute and late toxicities compared to standard of care treatment alone assessed by CTCAE Toxicity 5.0.	5 years
Time to Testosterone Recovery	Determine time to testosterone recovery with the use of standard of care treatment, with or without ARPI (abiraterone or enzalutamide).	5 years
Improvement in Metabolic Parameters	Determine if a statin (atorvastatin) with short-term ARPI (abiraterone) and standard of care treatment results in improved metabolic parameters (e.g. lipid profile, fasting glucose) and lower occurrence of cardiovascular events compared to short-term ARPI and standard of care treatment, alone.	5 years
Circulating Cell-Free DNA	Determine if a statin (atorvastatin) with short-term ARPI (abiraterone) and standard of care treatment results in lower levels of circulating cell-free DNA compared to short-term ARPI and standard of care treatment, alone.	2 years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Astellas Pharma Inc

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2023
• Primary Completion (Estimated): February 1, 2031
• Study Completion (Estimated): February 1, 2031

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: May 30, 2022
• First Posted (Actual): June 3, 2022

Study Record Updates

• Last Update Posted (Actual): July 27, 2026
• Last Update Submitted That Met QC Criteria: July 23, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• 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; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Azoles; Pharmacologic Actions; Chemical Actions and Uses; Pyrroles; Heptanoic Acids; Atorvastatin; Androgen Antagonists; abiraterone
• Other Study ID Numbers: 22-5274

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No