Duration of Enzalutamide and ADT With Metastasis Directed Therapy in Oligometastatic Cancer of the Prostate (DIRECT)

Study Overview
=================
Brief Summary
-----------------
This is a multi-centre, investigator-initiated, two-arm, randomized trial to investigate the addition on enzalutamide 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) or standard of care radiation and hormone (ADT) therapy plus oral enzalutamide for 8 months (Arm 2). Participants will be routinely follow-up in clinic or remotely for up to 5 years.

Official Title
-----------------
Duration of Enzalutamide and ADT With Metastasis Directed Therapy in Oligometastatic Cancer of the Prostate

Conditions
-----------------
Metastatic Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Enzalutamide
* Other: Standard of Care SBRT and ADT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 years Able to provide informed consent Histologic diagnosis of prostate adenocarcinoma ECOG performance status 0-2 Stage IV castrate sensitive metachronous metastatic prostate cancer. diagnosed within 6 months of study enrollment with 1-10 metastases Maximum one metastatic deposit on conventional imaging (CT or bone scan or MR) Additional metastases can be detectable by PSMA PET only All sites of disease are amenable to and can be safely treated with radiotherapy Patients decline continuous use of ADT Exclusion Criteria: Significant comorbidities rendering patient not suitable for ADT, enzalutamide and SBRT History of malignancy within the past 5 years, excluding non-melanoma skin cancer and in-situ cancer, managed non-curatively Prior use of salvage systemic therapy Evidence of spinal cord compression

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm 1 - Standard of Care<br>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 4 months as per standard of care (for 8 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<br>* Standard of care stereotactic body radiation therapy (SBRT) and androgen deprivation therapy (ADT)<br>|
| Experimental: Arm 2 - Study Treatment<br>Participants in this group will receive standard of care radiation treatment and ADT, plus enzalutamide. Participants will start ADT first. Androgen deprivation therapy will be delivered via injection every 4 months as per standard of care (for 8 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 enzalutamide orally (by mouth) daily for 8 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. | Drug: Enzalutamide<br>* Second-generation androgen pathway inhibitor (ARAT), oral tablet<br>Other: Standard of Care SBRT and ADT<br>* Standard of care stereotactic body radiation therapy (SBRT) and androgen deprivation therapy (ADT)<br>|

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 intermittent enzalutamide 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 intermittent enzalutamide 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 (EPIC-26). | 5 years | 
| Patient-reported quality of life | Determine if the addition of intermittent enzalutamide 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 intermittent enzalutamide 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 intermittent enzalutamide 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 |