Evolution of Hypofractionated Stereotactic Irradiation for Radio-Resistant Brain Metastases From D1-3-5 to D1-2-3

NCT ID: NCT07167134

Last Updated: 2025-09-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

264 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-31

Study Completion Date

2030-04-30

Brief Summary

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The goal of this prospective, multi-center, randomized double-arm clinical trial is to demonstrate a benefit in term of local control of a shorter spread of hypofractionated stereotactic radiotherapy at D1-2-3 vs D1-3-5, in the treatment of "radioresistant" Brain Metastases (BM). This trial aims to recruit patients with 1 to 5 unoperated BM originating from radioresistant primary sites. Patients will be randomly assigned to either the D1-3-5 radiotherapy arm or the D1-2-3 radiotherapy arm. Stereotactic brain irradiation will be administered at a dose of 33 Gy delivered in 3 fractions.

Detailed Description

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Brain metastases (BM), originating from various primary tumors, are associated with decreased progression-free survival, overall survival, and neurological function. Stereotactic radiotherapy offers a precise and targeted approach to treat BM while minimizing cognitive side effects. Studies have shown comparable local control rates to surgery and conventional radiotherapy, but radioresistant cancers exhibit lower response rates whatever the technique of radiotherapy. The radiobiological implications of treatment duration in brain stereotactic irradiation remain understudied, resulting in a lack of available data. However, there is potential for a shorter irradiation duration to enhance tumor control without an accompanying increase in treatment-related toxicity. This study aims to demonstrate a benefit in terms of local control of a shorter spread of hypofractionated stereotactic radiotherapy at D1, D2, D3 vs D1, D3, D5, in the treatment of radioresistant brain metastases.

This prospective, multi-center, randomized, double-arm clinical trial aims to recruit patients with 1 to 5 unoperated brain metastases originating from radioresistant primary sites. Patients will be randomly assigned to either the D1,3,5 radiotherapy arm or the D1,2,3 radiotherapy arm and will be followed for 2 years. Stereotactic brain irradiation will be administered at a dose of 33 Gy delivered in 3 fractions at the isocenter.

The primary endpoint of the study is the assessment of local control at 6 months per brain metastasis. Secondary endpoints include evaluating cerebral control, overall survival, radionecrosis rate, quality of life, neurological function, and treatment-related toxicity.

A more condensed treatment approach may exploit the radiobiological properties of tumors, potentially increasing their sensitivity to radiation while minimizing the opportunity for tumor repopulation. Moreover, reducing treatment duration also has the potential to improve the patient's quality of life by minimizing fatigue towards the end of the irradiation course.

Conditions

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Brain Metastases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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D1-3-5 radiotherapy

The prescribed total dose will be 23.1 Gy delivered in 3 fractions of 7.7 Gy on days 1, 3, and 5\*\*. The prescription will be based on 70% isodose line, resulting in a total dose of 33 Gy at the isocenter.

Group Type ACTIVE_COMPARATOR

D1-3-5 radiotherapy

Intervention Type RADIATION

23.1 Gray (Gy) delivered in 3 fractions of 7.7 Gy at D1, D3, and D5

D1-2-3 radiotherapy

The prescribed dose will be 23.1 Gy at delivered in 3 fractions of 7.7 Gy on days 1, 2, and 3\*. The prescription will be based on 70% isodose line, resulting in a total dose of 33 Gy at the isocenter.

Group Type EXPERIMENTAL

D1-2-3 radiotherapy

Intervention Type RADIATION

23.1 Gray (Gy) delivered in 3 fractions of 7.7 Gy at D1, D2, and D3

Interventions

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D1-3-5 radiotherapy

23.1 Gray (Gy) delivered in 3 fractions of 7.7 Gy at D1, D3, and D5

Intervention Type RADIATION

D1-2-3 radiotherapy

23.1 Gray (Gy) delivered in 3 fractions of 7.7 Gy at D1, D2, and D3

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* Age \> 18 years
* Patients with one or more unoperated brain metastases (1-5) originating from radioresistant primary locations, including melanoma, kidney, digestive, sarcoma, and prostate \*
* Karnofsky Performance Status (KPS) greater than 50% (Annex 3).
* Absence of major psychiatric conditions in the medical history that may interfere with follow-up, based on the investigator's judgement.
* Proficiency in understanding French.
* Signed informed consent.
* For the ancillary study only: Patients included in the SISMIC study at centers with adequate resources and who have agreed to participate in the optional ancillary study.

* Note: Patients who have had one or more surgery for metastasis removal and also have unresectable metastases are eligible for inclusion. Irradiation of the operating bed will follow the same treatment regimen as existing metastases but will not be considered for the evaluation of local control.

Exclusion Criteria

* Pregnant or breastfeeding women
* An unoperated brain metastasis whose maximum diameter is \> 3.5 cm
* Patients deprived of liberty or under guardianship (including curatorship).
* Patients with a history of cerebral radiotherapy.
* Patients with known allergy to gadolinium.
* Contraindication to magnetic resonance imaging (MRI).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre Paul Strauss

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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ICANS

Strasbourg, , France

Site Status

Countries

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France

Central Contacts

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Anne ANTHONY

Role: CONTACT

(0)388252413 ext. 33

Manon VOEGELIN

Role: CONTACT

(0)3 68 33 95 23 ext. 33

Facility Contacts

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Jordan EBER

Role: primary

(0)368766767 ext. 33

Other Identifiers

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2021-014

Identifier Type: -

Identifier Source: org_study_id

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