External Beam and Radioligand Radiotherapy for mCRPC
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: External Beam Radiotherapy Delivered Between Cycles of Radioligand Radiotherapy, Standard of care 177Lutetium-PSMA.
- Who it may be relevant to
- Registry conditions: Prostate Cancer Metastatic Castration-Resistant. Basic parameters: No limits · Male.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Canada
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Adaptive External Beam and Radioligand Radiotherapy for MEtaSTatic Castration Resistant Prostate Cancer (ARREST): a Phase II Registry-based RCT
Overview
Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy with Lutetium-177 (¹⁷⁷Lu-PSMA) is an established treatment for metastatic prostate cancer. Administered intravenously, it enables targeted irradiation of PSMA-expressing tumor cells. However, 30-50% of patients derive limited benefit. This variability could be partly explained by heterogeneity in delivered dose across lesions, leading to under-treatment of certain metastases. The addition of targeted external beam radiotherapy (EBRT) may compensate for this underdosing by delivering a precise dose to insufficiently irradiated lesions. We hypothesize that the addition of adaptive EBRT to ¹⁷⁷Lu-PSMA will reduce the incidence of skeletal-related events (pathologic fracture, spinal cord compression, surgery, or palliative radiotherapy) without increasing toxicity. 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 2026. Patients who are receiving SOC 177Lu-PSMA with targetable metastatic burden identified on imaging suitable for EBRT will be eligible. One hundred and twenty eligible patients will be randomized 1:1 to receive either SOC 177Lu-PSMA therapy alone (maximum 6 cycles) or to combined 177Lu-PSMA plus adaptive EBRT. 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 ≥50 Gy (α/β = 5) with priority to dose limits for organs at risk. A maximum treatment time of 60 minutes is permitted for each adaptive EBRT 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 overall survival, 177Lu-SPECT-CT and PSA response, toxicity, and quality of life. The sample size is designed to detect a 12 month improvement in the rate of skeletal related events with a HR 0.61, one-sided alpha of 0.1 and 80% power. 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.
Interventions
- Radiation External Beam Radiotherapy Delivered Between Cycles of Radioligand Radiotherapy
Adaptive EBRT dose based on 177Lutetium dosimetry - Radiation Standard of care 177Lutetium-PSMA
Per Standard of care
Primary outcome measures
- Skeletal Related Events [Time frame: 12 months]
Secondary outcome measures (5)
- Adverse Events [Time frame: 12 months]
- Overall suvival [Time frame: 24 months]
- PSA Response [Time frame: week 12]
- CR/PR on SPECT-CT [Time frame: After 3 cycles]
- Quality of Life Questionnaires [Time frame: 12 and 24 months]
Eligibility criteria
Inclusion criteria
- Receiving 177Lu-PSMA for mCRPC
- ECOG 0-1
- Presence of a discernible metastatic burden suitable for EBRT
- Receiving bone protective therapy
Exclusion criteria
- no exclusions
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Canada · 1 center
- Centre Hospitalier de l'Université-de-Montréal — Montreal
Identifiers
NCT: NCT07354594 · 2026-13179