External Beam and Radioligand Radiotherapy for mCRPC

NCT07354594 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2026-13179
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer Metastatic Castration-Resistant

Keywords

radiotherapy; radioligand therapy

Outcome Measures

Primary Outcomes (1)

• Skeletal Related Events

  12 months

Secondary Outcomes (5)

• Adverse Events

  12 months

• Overall suvival

  24 months

• PSA Response

  week 12

• CR/PR on SPECT-CT

  After 3 cycles

• Quality of Life Questionnaires

  12 and 24 months

Study Arms (2)

Standard of care 177Lutetium-PSMA

ACTIVE COMPARATOR

Radiation: Standard of care 177Lutetium-PSMA

EBRT + 177Lutetium-PSMA

EXPERIMENTAL

Radiation: External Beam Radiotherapy Delivered Between Cycles of Radioligand Radiotherapy

Interventions

Standard of care 177Lutetium-PSMA RADIATION

Per Standard of care

Standard of care 177Lutetium-PSMA

External Beam Radiotherapy Delivered Between Cycles of Radioligand Radiotherapy RADIATION

Adaptive EBRT dose based on 177Lutetium dosimetry

EBRT + 177Lutetium-PSMA

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Receiving 177Lu-PSMA for mCRPC
• ECOG 0-1
• Presence of a discernible metastatic burden suitable for EBRT
• Receiving bone protective therapy

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead
• Varian, a Siemens Healthineers Company: collaborator

Study Sites (1)

Centre Hospitalier de l'Université-de-Montréal

Montreal, Quebec, H2X 3E4, Canada

Location

Study Officials

• Cynthia Menard, MD

  Centre hospitalier de l'Université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mom Phat

CONTACT

514-890-8000; mom.phat.chum@ssss.gouv.qc.ca

Eva Nkurunziza

CONTACT

514-890-8000; eva-sabrina.nkurunziza.chum@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: January 21, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: April 8, 2026

Record last verified: 2026-01

Locations

CA (1)