Consolidative Use of Radiotherapy to Block Oligoprogression in Patients With Metastatic Melanoma (CURB-Melanoma)

Consolidative Use of Radiotherapy to Block Oligoprogression in Patients With Metastatic Melanoma (CURB-Melanoma) - a Phase 2 Clinical Trial

This open-label, prospective, single-arm Phase II trial explores whether adding stereotactic body radiotherapy (SBRT) or hypofractionated radiotherapy to oligoprogressive lesions can help delay disease progression in patients with metastatic melanoma. Participants may have up to ten extracranial oligoprogressive sites, with no upper limit on the total number of metastatic lesions. The study aims to assess whether targeting these progressing sites with focused radiotherapy can extend progression-free survival in this patient population.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Melanoma; OligoProgressive Metastatic Disease
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy (SBRT)

Detailed Description

This study evaluates the use of stereotactic body radiotherapy (SBRT) or hypofractionated radiotherapy in patients with metastatic melanoma who have up to 10 extracranial oligoprogressive lesions while receiving first-line systemic therapy. Oligoprogression refers to progression at a limited number of sites, while the remaining disease remains controlled by systemic treatment.

Participants will continue their current systemic therapy and receive SBRT or hypofractionated radiotherapy to all oligoprogressive lesions. The study will assess whether this approach can delay overall disease progression and extend the duration of benefit from ongoing systemic therapy.

Imaging will be used to monitor disease progression, and blood samples will be collected at baseline, after radiation, and at disease progression for exploratory analysis. Additional outcomes include overall survival, time on current therapy, toxicity, quality of life, and out-of-field response.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jillian C Tsai, MD; Phone Number: 4866 416-946-4501; Email: jillian.tsai@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Recruiting
      • University Health Network
      • Contact: Jillian C Tsai, MD; Phone Number: 4866 416-946-4501; Email: jillian.tsai@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 or older
• ECOG 0-2
• Willing and able to provide informed consent
• Metastatic melanoma detected on imaging and clinically confirmed.
• Treated with first line immunotherapy or BRAF inhibitors.
• No upper limit to the number of total metastatic sites, but a maximum of ten progressive metastatic sites, inclusive of primary disease and metastatic lesions, all of which must be extra cranial.
• Patients who had any prior radiation therapy near or overlapping with the oligoprogressive sites are allowed to enroll.
• All sites of oligoprogression that can be safely treated with SBRT or hypofractionated radiotherapy.

Exclusion Criteria:

• >10 extracranial sites of progressive disease.
• Pregnancy.
• Leptomeningeal disease.
• Serious medical comorbidities precluding radiotherapy, such as ataxia-telangiectasia or scleroderma.
• Prior radiotherapy near the oligoprogressive lesion precluding SBRT or hypofractionated radiotherapy due to exceeding OAR tolerance.
• Any psychological, sociological or geographical issue potentially hampering compliance with the study.
• Any other condition which in the judgment of the investigator would make the patient inappropriate for entry into this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single Arm; This is a single-arm trial, meaning all participants will receive the same treatment. There is no control or comparison group. All eligible patients will continue their existing first-line systemic therapy and receive additional radiation treatment-either stereotactic body radiotherapy (SBRT) or hypofractionated radiotherapy-directed at oligoprogressive lesions. The outcomes will be measured and analyzed based on this single group.

Radiation: Stereotactic Body Radiation Therapy (SBRT); SBRT will be delivered as per institutional standard.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) assessed by radiological imaging using RECIST v1.1 criteria	To determine if the addition of SBRT or hypofractionated radiation to progressive lesions improves progression-free survival in patients with metastatic melanoma. Radiological progression will be evaluated using CT, PET-CT, or MRI according to RECIST v1.1.	From enrollment up to 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS) measured from date of enrollment to death from any cause	Enrollment up to 24 months
Time on Current Systemic Therapy After Initial Oligoprogression	From enrollment up to 24 months
Out-of-field response assessed by radiological imaging (CT, PET-CT, or MRI)	From enrollment up to 24 months.
Participant-reported adverse events measured using PRO-CTCAE questionnaire	From baseline through follow-up (up to 24 months)
Participant-reported quality of life measured using EORTC QLQ-C30 questionnaire	From baseline through follow-up (up to 24 months)
Reporting acute and late toxicities of SBRT	Enrollment up to 24 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2025
• Primary Completion (Estimated): July 24, 2027
• Study Completion (Estimated): July 24, 2028

Study Registration Dates

• First Submitted: July 29, 2025
• First Submitted That Met QC Criteria: August 6, 2025
• First Posted (Actual): August 8, 2025

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Melanoma; stereotactic body radiation therapy (SBRT)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: 25-5162

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No