Prostate Cancer Metastatic Castration-ResistantPhase 2ARRESTNCT07354594
External Beam and Radioligand Radiotherapy for mCRPC
A Phase 2 study testing External Beam Radiotherapy Delivered Between Cycles of Radioligand Radiotherapy in people with Prostate Cancer Metastatic Castration-Resistant, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Prostate Cancer Metastatic Castration-Resistant
- What is being tested?
- External Beam Radiotherapy Delivered Between Cycles of Radioligand Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteCanada
- Study dates
- 7 Jul 2026to May 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Receiving 177Lu-PSMA for mCRPC
- ECOG 0-1
- Presence of a discernible metastatic burden suitable for EBRT
- Receiving bone protective therapy
Who cannot join
- no exclusions
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Centre Hospitalier de l'Université-de-Montréal
Montreal, Quebec, H2X 3E4
Mom Phat, 514-890-8000 ext. 11171, mom.phat.chum@ssss.gouv.qc.ca
Eva Nkurunziza, 514-890-8000 ext. 30898, eva-sabrina.nkurunziza.chum@ssss.gouv.qc.ca
About this study
Official title: Adaptive External Beam and Radioligand Radiotherapy for MEtaSTatic Castration Resistant Prostate Cancer (ARREST): a Phase II Registry-based RCT
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.
The investigators 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.
Read more
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 receiving standard-of-care (SOC) ¹⁷⁷Lu-PSMA with targetable metastatic burden identified on imaging and 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 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 chosen based on a set of criteria that include estimated suboptimal absorbed dose from ¹⁷⁷Lu-PSMA, lesions demonstrating low PSMA but high FDG uptake, symptomatic lesions, and lesions at high risk for skeletal-related events. Selected lesions will receive single-fraction EBRT. The prescribed dose will range from 6-12 Gy, with the goal of achieving a combined total biological effective dose of ≥50 Gy (α/β = 5), while prioritizing 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 who achieve a complete response, as measured by ¹⁷⁷Lu-SPECT-CT and PSA, will pause ARREST treatment and resume at disease 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 hazard ratio of 0.61, a one-sided alpha of 0.1, and 80% power.
ARREST is expected 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 effects on tissues, thereby refining the relative biological effectiveness model for more precise treatment planning.
- Being tested
- External Beam Radiotherapy Delivered Between Cycles of Radioligand Radiotherapy, Standard of care 177Lutetium-PSMA
- Keywords
- radiotherapy, radioligand therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
External Beam Radiotherapy Delivered Between Cycles of Radioligand RadiotherapyRadiation
Adaptive EBRT dose based on 177Lutetium dosimetry
Standard of care 177Lutetium-PSMARadiation
Per Standard of care
| Study group | Role | What they receive |
|---|---|---|
| Standard of care 177Lutetium-PSMA | Active comparator | Not described Receives: Radiation: Standard of care 177Lutetium-PSMA |
| EBRT + 177Lutetium-PSMA | Experimental | Not described Receives: Radiation: External Beam Radiotherapy Delivered Between Cycles of Radioligand Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Skeletal Related Events
Measured: 12 months
Secondary outcomes (5)
Adverse Events
CTCAE Grade 2+ events
Measured: 12 months
Overall suvival
Measured: 24 months
PSA Response
Proportion of patients achieving a >'50% PSA decline
Measured: week 12
CR/PR on SPECT-CT
Measured: After 3 cycles
Quality of Life Questionnaires
EORTIC QLQ-C30, PRO-CTCAE
Measured: 12 and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2026
- Study start7 Jul 2026
- Primary completionMay 2028 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate Cancer Metastatic Castration-ResistantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)
- Sponsor type
- University, hospital or other
- Collaborators
- Varian, a Siemens Healthineers Company
- Responsible party
- Sponsor
- Investigators
- Cynthia Menard, MD, Principal investigator, Centre hospitalier de l'Université de Montréal (CHUM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07354594
- Sponsor's protocol ID
- 2026-13179
- Acronym
- ARREST
- Status last verified
- Jan 2026
- First submitted
- 17 Nov 2025
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided