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

Phase 2RecruitingNCT05404139

University Health Network, Toronto352 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

352

Conditions

Metastatic Prostate Cancer

Interventions

Eligibility

Sex: MALEMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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

Locations (2)

Princess Margaret Cancer Center

Toronto, Ontario, Canada

RECRUITING

Sunnybrook Research Institute

Toronto, Ontartio, Canada

ACTIVE_NOT_RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: 5 years

Secondary Outcomes

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).

Time frame: 5 years

Patient-reported quality of life

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 2 years

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

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts