Radiotherapy for Prostate Cancer
(ARREST Trial)
What You Need to Know Before You Apply
What is the purpose of this trial?
Introduction 177Lu-PSMA radioligand therapy (RLT) is an emerging option for metastatic castration-resistant prostate cancer (mCRPC). However, up to half of patients fail to show meaningful clinical benefit with this therapy. A dual-modality strategy seeks to increase dose via complementary external beam radiotherapy (EBRT) in underdosed tumor regions. We hypothesize that by combining both modalities (EBRT and RLT) in an hybrid, adaptive approach, we can safely improve skeletal related events when compared to standard-of-care (SOC) 177Lu-PSMA alone.
Methodology Adaptive EBRT and RLT for mCRPC (ARREST) is a pragmatic registry-based phase 2, multi-center randomized controlled trial within the PERa prospective cohort (NCT03378856) planned to activate in 2025. Patients who are receiving SOC 177Lu-PSMA with targetable metastatic burden identified on imaging suitable for EBRT will be eligible. One hundred and thirty eligible patients will be randomized 1:1 to receive either SOC 177Lu-PSMA therapy alone (maximum 6 cycles) or to combined 177Lu-PSMA plus EBRT boost. Patients in the experimental arm will undergo FDG-PET at study entry and SPECT-CT after each cycle of radioligand therapy. Lesions selected for EBRT boost will be selected based on a set of criteria that include estimated suboptimal dose absorbed from 177LuPSMA, lesions demonstrating low PSMA but high FDG update, symptomatic lesions, and those at high risk for skeletal-related events. Selected lesions will receive single-fraction EBRT. Dose prescribed will range from 6-12 Gy with the ideal goal of a combined total biological effective dose of ≥75 Gy (α/β = 1.4) with priority to dose limits for organs at risk. A maximum treatment time of 60 minutes is permitted for each EBRT boost treatment. Patients in the experimental arm that achieve complete response measured by 177Lu-SPECT-CT and PSA will pause ARREST and resume at progression. The primary endpoint is skeletal related events at 1 year. Secondary objectives include overal survival, 177Lu-SPECT-CT and PSA response, toxicity, and quality of life. The sample size is designed to detect a 12 month imporvement in the rate of skeletal related events with a HR 1.6, two-sided alpha of 0.1 and 80% power.
Conclusion ARREST is hypothesized to safely optimize tumor dose, offering a personalized hybrid approach that may lead to improved patient outcomes. In addition, this study will permit further understanding of these two distinct radiation delivery methods and their effect on tissues, thereby refining the relative biological effectiveness model for more precise treatment planning.
Who Is on the Research Team?
Cynthia Menard, MD
Principal Investigator
Centre hospitalier de l'Université de Montréal (CHUM)
Are You a Good Fit for This Trial?
This trial is for men with metastatic castration-resistant prostate cancer (mCRPC) who can undergo radioligand therapy and have tumors suitable for external beam radiotherapy. Patients must be part of the PERa cohort, able to receive standard-of-care 177Lu-PSMA, and have targetable metastases on imaging.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive either SOC 177Lu-PSMA therapy alone or combined 177Lu-PSMA plus EBRT boost, with a maximum of 6 cycles
Follow-up
Participants are monitored for skeletal related events, overall survival, PSA response, toxicity, and quality of life
What Are the Treatments Tested in This Trial?
Interventions
- 177Lu-PSMA radioligand therapy
- External Beam Radiotherapy
Trial Overview
The ARREST trial tests if adding external beam radiotherapy to standard radioligand therapy improves outcomes in mCRPC. It's a phase 2 study where patients are randomly chosen to get either just the standard treatment or combined with targeted radiation boosts.
How Is the Trial Designed?
2
Treatment groups
Experimental Treatment
Active Control
Find a Clinic Near You
Who Is Running the Clinical Trial?
Centre hospitalier de l'Université de Montréal (CHUM)
Lead Sponsor
Varian, a Siemens Healthineers Company
Industry Sponsor
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