Hypofractionated (3×10 Gy) versus single‑dose (20–25 Gy) stereotactic radiotherapy for limited brain metastases

Stereotactic Radiotherapy in Oligometastatic Brain Disease: a Randomised Phase III Study Comparing Hypofractionated Stereotactic Radiation Therapy (3*10 Gy) to the Historical Single-dose Radiosurgery (1*20 to 25 Gy) With Medico-economic Evaluation.

This trial will try whether giving stereotactic radiotherapy in three 10 Gy sessions works as well or better than the traditional single high‑dose (20–25 Gy) radiosurgery for adults with up to five small brain metastases.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 504 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre Francois Baclesse (other)
• Drugs / interventions: radiation
• Locations: 15 sites (Bordeaux and 14 other locations)
• Trial ID: NCT05102747 on ClinicalTrials.gov

What this trial studies

This randomized phase III trial compares hypofractionated stereotactic radiotherapy (3×10 Gy) to the historical single‑dose stereotactic radiosurgery (20–25 Gy) for patients with up to five brain metastases. Eligible lesions are generally 10–25 mm with a maximum cumulative gross tumor volume of 30 cm3, and patients must have good performance status and no bleeding lesions or meningeal carcinomatosis. The protocol includes standard target definition and delivery of stereotactic radiotherapy and will record tumor control, neurological function, toxicity, and health‑economic outcomes. Results aim to inform decisions about dose fractionation by balancing tumor control, side effects, patient convenience, and cost.

Who should consider this trial

Good fit: Adults (≥18 years) with WHO performance status 0–1 who are eligible for stereotactic radiotherapy and have 1–5 solid tumor brain metastases (typically 10–25 mm, cumulative GTV ≤30 cm3) without bleeding or meningeal carcinomatosis are ideal candidates.

Not a fit: Patients with more than five brain metastases, active bleeding lesions or leptomeningeal disease, poor performance status, or those requiring whole‑brain radiotherapy or immediate surgery are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the hypofractionated approach could provide similar or better tumor control with lower toxicity, better functional preservation, and greater convenience compared with single‑dose radiosurgery.

How similar studies have performed: Retrospective series and smaller prospective cohorts suggest hypofractionated SRT can improve safety and local control for certain lesion sizes, but a direct randomized phase III comparison with single‑dose SRS has been lacking.

Eligibility criteria

Inclusion Criteria:

* Patients aged ≥ 18 years
* WHO performance status 0 or 1;
* Patient eligible for SRT after a multidisciplinary committee decision; Patient with BMs from radioresistant cancer (renal cell carcinoma, sarcoma, melanoma) is eligible
* Patient having up to 5 BM of solid tumours with an histologically proven diagnoses; patients who have had a metastasectomy and having 1 to 4 BM lesions is eligible (ANOCEF recommendations); post-operative cavity must be treated by radiosurgery according to local procedures with respect of non-inclusion criteria\* (cavity will not be analyzed for efficacy)
* Presence of at least one and no more than 5 target lesions for SRT, measuring between 10 and 25 mm. In the event of synchronous BM, lesions measuring less than 10mm or more than 25mm (1 to 4 lesions) will be treated at the discretion of the investigator
* Max cumulative GTV of 30cm3
* Normal complete blood count (CBC)
* Absence of bleeding BM or meningeal carcinomatosis;
* Symptomatic BM are allowed
* DS-GPA score:

  * Renal cancer: DS-GPA 2,5 or more
  * Breast cancer: DS-GPA 2,5 or more
  * Melanoma: DS-GPA 1.5 or more
  * Gastro-instestinal (GI) cancer: DSGPA 3 or more
  * Adenocarcinoma lung cancer: DS-GPA 2 or more (DS-GPAmol)
  * Squamous lung cancer : DS-GPA 2,5 or more (DS-GPAmol)
  * For cancers where the DS-GPA score is not applicable, the patient is eligible if eligibility criteria are met
* Patient with no concomitant systemic treatment; in case of ongoing systemic treatment, wash out period of 3-7 days before and after SRT, depending of drug and at the discretion of investigator;
* Patient sufficiently cooperating to perform the treatment with the use of a thermoformed mask;
* Patient whose neuropsychological abilities allow to follow the requirements of the protocol;
* Female with childbearing potential must use adequate contraception
* Signed informed consent formOligoBM-01 Trial - ID-RCB number: 2021-A01622-39 - version 3.1 dated from 2023-06-22 Page 9 of 51
* Patients affiliated to the social security system

Exclusion Criteria:

* Patients with current or past history small cell lung cancer, germ-cell tumours, lymphoma, leukemia and multiple myeloma within the last 5 years;
* Patients with metastases in the brain stem, or within 1 cm of the optic apparatus;
* Patients with an associated neurodegenerative disease;
* Any symptoms not attributable to BM or cancer disease requiring long term corticosteroid use (regardless of dose);
* Contraindication to perform the brain MRI or gadolinium or iodinated contrast;
* Known hypersensitivity to the contrast product or to any their excipients
* Patients with previous brain stereotactic irradiation
* Whole brain irradiation history;
* Haemorrhagic metastasis;
* Ongoing anti angiogenic treatment (treatment should be held 3-7 days before irradiation and re-initiated 3-7 days after irradiation for patient to be eligible);
* Patients with too close brain lesions for whom a treatment plan on one target metastasis delivers a dose \> 5 Gy on other concomitant metastasis ;
* Patient deprived of liberty or under guardianship;
* Known pregnancy or breastfeeding
* Any geographical conditions, social and associated psychopathology that may compromise the patient's ability to participate in the study;
* Participation in a therapeutic trial for less than 30 days.
* Patient deprived of freedom or under guardianship

Where this trial is running

Bordeaux and 14 other locations

• CHU — Bordeaux, France (NOT_YET_RECRUITING)
• Institut Bergonié — Bordeaux, France (NOT_YET_RECRUITING)
• CHU — Brest, France (RECRUITING)
• Centre François Baclesse — Caen, France (RECRUITING)
• CHU — Grenoble, France (NOT_YET_RECRUITING)
• Centre Guillaume le Conquérant — Le Havre, France (RECRUITING)
• Groupe hospitalier Bretagne Sud — Lorient, France (RECRUITING)
• Centre Antoine Lacassagne — Nice, France (NOT_YET_RECRUITING)
• La Pitié Salpétrière — Paris, France (NOT_YET_RECRUITING)
• Centre hospitalier Lyon Sud — Pierre-Bénite, France (NOT_YET_RECRUITING)
• Centre Eugène Marquis — Rennes, France (RECRUITING)
• Centre Henri Becquerel — Rouen, France (NOT_YET_RECRUITING)
• Centre d'Oncologie et Radiothérapie Saint-Jean — Saint-Doulchard, France (RECRUITING)
• Institut Claudius Regaud — Toulouse, France (NOT_YET_RECRUITING)
• Gustave Roussy — Villejuif, France (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Dinu STEFAN, MD

Conditions: Brain Metastasis, Oligoprogression, Stereotactic radiosurgery, Fractionated stereotactic radiotherapy