Prophylactic Radiotherapy to Prevent Bone Complications in Patients With Metastatic Solid Cancers (pRevenT)

A Randomized Controlled Trial of Early Prophylactic Radiotherapy to Prevent Bone Complications in Patients With Metastatic Solid Cancers

This is a prospective, randomized, single-center clinical trial evaluating whether early prophylactic radiotherapy to high-risk asymptomatic or minimally symptomatic bone metastases reduces the 1-year rate of skeletal-related events (SREs) in patients with metastatic solid cancers. Patients will be randomized in a 1:1 ratio to receive either standard of care systemic therapy or observation, or prophylactic radiotherapy in addition to standard of care. The primary endpoint is the 1-year rate of SREs. Secondary endpoints include adverse events, quality of life, economic burden, pain-free survival, and overall survival.

Study Overview

• Status: Not yet recruiting
• Conditions: Bone Metastases; Metastatic Solid Tumor
• Intervention / Treatment: Radiation: Prophylactic External Beam Radiotherapy; Other: Standard of Care

Detailed Description

Bone metastases are a common complication in patients with metastatic solid cancers and are associated with significant morbidity, including skeletal-related events (SREs) such as pathological fractures, spinal cord compression, and severe pain requiring intervention. While palliative radiotherapy is an established treatment for symptomatic bone metastases, the role of prophylactic radiotherapy in asymptomatic or minimally symptomatic high-risk lesions remains insufficiently defined.

This prospective, randomized, single-center phase II clinical trial evaluates the effectiveness of early prophylactic radiotherapy in reducing the incidence of SREs. Eligible patients with metastatic solid cancers and up to five high-risk asymptomatic or minimally symptomatic bone metastases will be randomized in a 1:1 ratio into two groups. The control group will receive standard of care systemic therapy or observation according to tumor type and clinical guidelines. The intervention group will receive prophylactic external-beam radiotherapy (25 Gy in 5 fractions) to selected high-risk bone metastases in addition to standard of care.

Patients will be followed from baseline up to 12 months, with assessments conducted at predefined intervals. Study outcomes include the incidence of SREs, adverse events (graded according to CTCAE), patient-reported outcomes using validated questionnaires (EORTC QLQ-C30, EQ-5D-5L, BPI), economic burden, pain-free survival, and overall survival.

This study aims to determine whether early radiotherapy intervention can prevent skeletal complications, reduce healthcare burden, and improve patient outcomes in metastatic bone disease.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eva Ćirić, MD; Phone Number: +38615879623; Email: eciric@onko-i.si
• Study Contact Backup: Name: Klavdija Korošec; Phone Number: +38631630065; Email: kkorosec@onko-i.si

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Institute of Oncology Ljubljana
    • Contact: Eva Ćirić, MD; Phone Number: +38615879623; Email: eciric@onko-i.si
    • Contact: Klavdija Korošec; Phone Number: +38631630065; Email: kkorosec@onko-i.si

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years
• Histologically confirmed solid malignancy
• Metastatic disease confirmed by imaging (CT, MRI, or PET-CT)
• Presence of up to five high-risk bone metastases
• High-risk bone metastases defined according to protocol criteria
• Asymptomatic or minimally symptomatic bone metastases (not requiring opioid analgesics)
• ECOG performance status 0-2
• Ability to provide written informed consent

Exclusion Criteria:

• Prior radiotherapy to the index bone metastases preventing safe treatment planning
• Symptomatic bone metastases requiring immediate palliative radiotherapy
• Evidence of spinal cord compression
• Bone metastases causing significant pain requiring opioid analgesics
• Oligometastatic disease suitable for radical treatment
• Leptomeningeal disease
• ECOG performance status ≥3
• Life expectancy less than 3 months
• Any condition that, in the investigator's opinion, would interfere with study participation or assessment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prophylactic Radiotherapy + Standard of Care; Participants receive prophylactic external-beam radiotherapy (25 Gy in 5 fractions) to up to five high-risk asymptomatic or minimally symptomatic bone metastases, in addition to standard of care systemic therapy or observation.	Radiation: Prophylactic External Beam Radiotherapy; External beam radiotherapy delivered to up to five high-risk asymptomatic or minimally symptomatic bone metastases at a total dose of 25 Gy in 5 fractions.; Other: Standard of Care; Systemic therapy or observation according to tumor type and clinical guidelines.
Active Comparator: Standard of Care; Participants receive standard of care systemic therapy or observation according to tumor type and clinical guidelines, without prophylactic radiotherapy.	Other: Standard of Care; Systemic therapy or observation according to tumor type and clinical guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year rate of skeletal-related events (SREs)	Number of participants experiencing at least one skeletal-related event (pathological fracture, spinal cord compression, need for radiation to bone, need for surgery to bone, or tumor-related hypercalcemia) within 12 months after randomization.	From randomization to 12 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Adverse events assessed and graded according to CTCAE version 6.0	Up to 12 months after randomization
EORTC QLQ-C30 global health status score	EORTC QLQ-C30 global health status score at each assessment time point (range: 0-100; higher scores indicate better quality of life).	Baseline, 3 months, 6 months, and 12 months after randomization
EQ-5D-5L index score	EQ-5D-5L index score at each assessment time point (range typically from <0 to 1; higher values indicate better health status).	Baseline and follow-up visits up to 12 months after randomization
Brief Pain Inventory (BPI) pain intensity score	Pain intensity score measured using the Brief Pain Inventory (scale 0-10; higher scores indicate worse pain).	Baseline and follow-up visits up to 12 months after randomization
Pain-free survival	Time from randomization to first occurrence of pain requiring opioid analgesics or death from any cause, whichever occurs first.	From randomization to 12 months after randomization
Overall survival	Time from randomization to death from any cause.	From randomization to 12 months after randomization
Healthcare resource utilization	Number and duration of hospitalizations, number of outpatient visits, and associated healthcare costs during the study period.	From randomization to 12 months after randomization

Collaborators and Investigators

• Sponsor: Institute of Oncology Ljubljana

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: April 2, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: prophylactic radiotherapy; early radiotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: ORI2025-23

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