Early radiotherapy versus observation for high‑risk painless or minimally painful bone metastases

Phase III Randomized Trial for High-risk Asymptomatic or Minimally Symptomatic Bone Metastases: Early Radiotherapy Versus Observation

This will test whether giving preventive radiotherapy to people with high‑risk but painless or minimally painful bone metastases can reduce future bone complications, hospital stays, and symptoms compared with observation and usual treatment.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cancer Research Antwerp (Academic / other)
• Drugs / interventions: radiation
• Locations: 8 sites (Wilrijk, Antwerp and 7 other locations)
• Trial ID: NCT07146074 on ClinicalTrials.gov

What this trial studies

This randomized interventional trial compares early targeted radiotherapy to observation with standard systemic care for patients with solid tumors who have polymetastatic disease and one or more high‑risk, asymptomatic or minimally symptomatic bone lesions. High‑risk lesions are defined by size and location (for example hip, shoulder, long bones, or junctional vertebrae), cortical involvement, or epidural extension, and target lesions must have pain ≤2 on the Numeric Rating Scale. The trial measures symptomatic skeletal events (pathologic fracture, spinal cord compression, need for palliative radiotherapy or orthopedic surgery), related hospitalizations, overall survival, health‑related quality of life, and treatment side effects. Participants receive either preventive radiotherapy to high‑risk sites plus usual care or observation/standard systemic therapy, with scheduled follow‑up to capture events and patient‑reported outcomes.

Who should consider this trial

Good fit: Adults with histologically confirmed solid tumors with polymetastatic spread (≥3 metastases) and one or more high‑risk bone metastases that are asymptomatic or minimally symptomatic (pain ≤2 for the lesion) fit the eligibility profile.

Not a fit: Patients who already have symptomatic, unstable, or imminently threatening bone lesions that need immediate local treatment, those with fewer than three metastases, or non‑solid tumor malignancies are unlikely to benefit from this preventive approach.

Why it matters

Potential benefit: If successful, early radiotherapy could prevent fractures, spinal cord compression and other skeletal events, reduce hospitalizations, and help preserve quality of life for people with high‑risk bone metastases.

How similar studies have performed: Some retrospective series and smaller prospective reports and routine clinical practice support local radiotherapy to prevent or treat skeletal complications, but large randomized evidence specifically testing preventive radiotherapy for asymptomatic high‑risk lesions is limited.

Eligibility criteria

Inclusion Criteria:

* I1: Histologically confirmed solid tumor malignancy (with polymetastastic spread (≥ 3 metastases))
* I2: High-risk bone metastasis(es) that is (are) asymptomatic or minimally symptomatic:

  \*Asymptomatic or minimally symptomatic is defined as follows: O Numeric Pain Rating Scale (NRS) score ≤2 for the specific lesion(s)

  \*High-risk is defined as follows (i.e. at least one of the following points must be applicable): O Bulky site of disease in bone (diameter ≥ 2 cm) O Disease involving the hip (acetabulum, femoral head, femoral neck), shoulder (acromion, glenoid, humeral head), or sacroiliac joints O Disease in long bones with cortical involvement of \>1/3 in proportion to the diameter of the bone (humerus, radius, ulna, clavicle, femur, tibia, fibula, metacarpals, phalanges) O Disease in vertebrae of the junctional spine (C1-2, C7- T1, T12-L1, L5-S1) and/or disease with posterior element involvement or epidural extension (Bilsky epidural compression score 1a-3) \[Bilsky et al\]. The posterior elements of the spine consist of the pedicles, laminae, facets (articular processes), transverse processes, and the spinous process.
* I3: Number of Risk Factors (NRF) prognostic score 0-2
* I4: Age ≥ 18 years
* I5: Ability to provide informed consent (either by the patient or by a legally authorized representative)
* I6: A female participant is eligible to participate if she confirms not to be pregnant at screening, and one of the following conditions applies:

Is not a woman of child bearing potential or A woman of child bearing potential must confirm that she is not pregnant at screening and must agree to use a very effective method of birth control

Exclusion Criteria:

* E1: Previous RT to the target treatment site(s)
* E2: NRF prognostic score 3
* E3: Serious medical co-morbidities that preclude radiotherapy
* E4: Bone lesion complicated with a pathological fracture or impending pathologic fracture for which prophylactic stabilization is recommended, characterized by Mirels score of ≥9 \[Mirels et al\].
* E5: Spinal metastasis with SINS score \>13 requiring upfront neurosurgical stabilization \[Fourney et al\].
* E6: More than 5 high-risk asymptomatic or minimally symptomatic metastatic bone locations
* E7: Patient already included in another clinical trial that would interfere with the HERMES clinical trial, as assessed by the Investigator.

Where this trial is running

Wilrijk, Antwerp and 7 other locations

• ZAS Augustinus — Wilrijk, Antwerp, Belgium (Recruiting)
• Azorg — Aalst, Belgium (Recruiting)
• UZ Gent — Ghent, Belgium (Recruiting)
• Jessa Ziekenhuis — Hasselt, Belgium (Not_yet_recruiting)
• AZ Groeninge — Kortrijk, Belgium (Recruiting)
• UZ Leuven Gasthuisberg — Leuven, Belgium (Not_yet_recruiting)
• AZ Delta — Roeselare, Belgium (Recruiting)
• AZ Turnhout — Turnhout, Belgium (Recruiting)

Study contacts

• Principal investigator: Charlotte Billiet, MD, PhD — Ziekenhuis aan de Stroom
• Study coordinator: Charlotte Billiet, MD, PhD

Conditions Solid Neoplasms; Bone Metastases; Asymptomatic or Minimally Symptomatic; High Risk for Skeletal Events; Bone metastases; Randomized; Radiotherapy; Symptomatic skeletal events