Early Radiotherapy Versus Observation for High-risk Asymptomatic or Minimally Symptomatic Bone Metastases

NCT07146074 | Recruiting

• 1 other identifier: CTO23032GZA
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 8

Brief Summary

The goal of this clinical trial is to learn whether radiotherapy (i.e. treatment with ionizing radiation to destroy cancer cells) can prevent symptoms in patients with metastatic cancer, having high-risk bone metastases that currently result in no or only mild symptoms. High-risk bone metastases are bone metastases at high-risk of developing bone complications, such as fractures or myelum compression. The main questions this study aims to answer are:

• Can preventive radiation of high-risk asymptomatic or minimally symptomatic bone metastases (and observation or medication) decrease the number of skeletal related events (i.e. bone complications due to bone metastases) in patients with metastatic cancer?
• Can preventive radiation of high-risk asymptomatic or minimally symptomatic bone metastases (and observation or medication) decrease the need for hospitalization related to such bone metastases, improve overall survival and (health-related) quality of life?
• What are the side effects of preventive radiation of high-risk asymptomatic or minimally symptomatic bone metastases? Researchers will compare 2 treatment groups in order to answer the questions listed above: 1 group treated with medication or observation alone (group A) and 1 group treated with medication or observation and preventive radiotherapy (group B). Participants will
• be screened to assess whether they are eligible to participate in the study.
• be randomized (i.e. drawn) into the 2 treatment groups mentioned above.
• be treated with preventive radiotherapy if they were drawn in treatment group B.
• need to attend follow-up visits (may be via teleconsultation) at 1, 3, 6, 12, 18 and 24 months after date of randomization during which safety and efficacy is monitored. During these follow-up visits, the general health condition of the participant is evaluated, the occurrence of any bone complication, the medications taken by the participant are registered, the degree of pain and location of the high-risk bone metastases are determined and possible side effects are registered. Furthermore, the participant needs to complete 2 questionnaires at each visit regarding his/her quality of life.

Conditions

Solid Neoplasms; Bone Metastases; Asymptomatic or Minimally Symptomatic; High Risk for Skeletal Events

Keywords

Bone metastases; Randomized; Radiotherapy; Symptomatic skeletal events; Preventive

Outcome Measures

Primary Outcomes (1)

• Time to a symptomatic skeletal related event (SSE) in any bone metastasis or death due to any cause whichever occurs first

  Time to an SSE in any bone metastasis or death due to any cause whichever occurs first. An exception are SSE in bone metastases that were already treated with surgery or radiotherapy before study participation.

  Measured from the date of randomization to the date when an SSE occurs in any bone metastasis, date of death due to any cause or last follow-up visit at 24 months after randomization whichever occurs first.

Secondary Outcomes (7)

• Need for hospitalization related to the high-risk bone metastasis(es).

  Measured from date of study randomization to last follow-up visit (24 months after randomization date), date of death of any cause or early end of participation in the study due to other reasons whichever occurs first.

• Overall survival (OS)

  Measured from time of study randomization to date of death of any cause or last follow-up visit (24 months after randomization date) whichever occurs first

• Quality of life (QoL) measurement by EORTC QLQ-C15-PAL questionnaire (physical and emotional function, dyspnoea, pain, sleeping difficulties, appetite, nausea/vomiting, constipation, fatigue)

  From screening until last follow-up visit (24 months after randomization date), date of death of any cause, early end of study participation due to other reason or unscheduled follow-up visit at 1 week after occurrence of an SSE whichever occurs first.

• Quality of life (QoL) measurement by EORTC QLQ-C15-PAL questionnaire (overall quality of life)

  From screening until last follow-up visit (24 months after randomization date), date of death of any cause, early end of study participation due to other reason or unscheduled follow-up visit at 1 week after occurrence of an SSE whichever occurs first.

• Quality of life measurement by EuroQol Group EQ-5D-5L questionnaire (mobility, self-care, usual activities, pain/discomfort, anxiety/depression).

  From screening until last follow-up visit (24 months after randomization date), date of death of any cause, early end of study participation due to other reason or unscheduled follow-up visit at 1 week after occurrence of an SSE whichever occurs first.

Study Arms (2)

Arm A: observational arm

ACTIVE COMPARATOR

Patients in arm A will receive either systemic therapy or observation.

Drug: Systemic therapy (Standard of Care)/Observation

Arm B: upfront radiotherapy arm

EXPERIMENTAL

Patients in arm B will receive preventive (upfront) radiotherapy in addition to either systemic therapy or observation.

Radiation: Preventive radiotherapy; Drug: Systemic therapy (Standard of Care)/Observation

Interventions

Preventive radiotherapy RADIATION

Either conventional radiotherapy (single dose of 8 Gy) or Stereotactic Ablative Body Radiation (either 1x20 Gy, 2x12 Gy, 3x10 Gy or 5x8 Gy) will be delivered depending on the participant's prognostic outcome.

Arm B: upfront radiotherapy arm

Systemic therapy (Standard of Care)/Observation DRUG

It concerns systemic therapy if applicable according to the standard of care or only observation.

Arm A: observational arm; Arm B: upfront radiotherapy arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cancer Research Antwerp: lead
• Kom Op Tegen Kanker: collaborator

Study Sites (8)

ZAS Augustinus

Wilrijk, Antwerp, 2610, Belgium

RECRUITING

AZORG

Aalst, 9300, Belgium

RECRUITING

UZ Gent

Ghent, 9000, Belgium

RECRUITING

Jessa Ziekenhuis

Hasselt, 3500, Belgium

NOT YET RECRUITING

AZ Groeninge

Kortrijk, 8500, Belgium

RECRUITING

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

NOT YET RECRUITING

AZ Delta

Roeselare, 8800, Belgium

RECRUITING

AZ Turnhout

Turnhout, 2300, Belgium

RECRUITING

Study Officials

• Charlotte Billiet, MD, PhD

  Ziekenhuis aan de Stroom

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charlotte Billiet, MD, PhD

CONTACT

034433759; cancertrials@zas.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: August 28, 2025
• Study Start: February 5, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

BE (8)