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

Study Purpose

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.#46;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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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).

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT07167134
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Centre Paul Strauss
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	France
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Brain Metastases

Additional Details

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.#46;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.

Arms & Interventions

Arms

Active Comparator: 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.

Experimental: 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.

Interventions

Radiation: - D1-3-5 radiotherapy

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

Radiation: - D1-2-3 radiotherapy

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

ICANS, Strasbourg 2973783, France

Status

Address

ICANS

Strasbourg 2973783, ,

Site Contact

Jordan EBER

[email protected]

(0)368766767 #33

Clinical Trial Finder