Brain MetastasesPhase 3SISMICNCT07167134
Evolution of Hypofractionated Stereotactic Irradiation for Radio-Resistant Brain Metastases From D1-3-5 to D1-2-3
A Phase 3 study testing D1-3-5 radiotherapy and D1-2-3 radiotherapy in people with Brain Metastases, run by Centre Paul Strauss at 1 site in France.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases
- What is being tested?
- D1-3-5 radiotherapy and D1-2-3 radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 264 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2025to Apr 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
ICANS
Strasbourg
Jordan EBER, (0)368766767 ext. 33, j.eber@icans.eu
About this study
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.
Read the detailed description
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
- Brain Metastases
- Being tested
- D1-3-5 radiotherapy, D1-2-3 radiotherapy
- Keywords
- hypofractionated stereotactic radiotherapy, treatment duration
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D1-3-5 radiotherapyRadiation
23.1 Gray (Gy) delivered in 3 fractions of 7.7 Gy at D1, D3, and D5
D1-2-3 radiotherapyRadiation
23.1 Gray (Gy) delivered in 3 fractions of 7.7 Gy at D1, D2, and D3
| Study group | Role | What they receive |
|---|---|---|
| D1-3-5 radiotherapy | Active comparator | 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. Receives: Radiation: D1-3-5 radiotherapy |
| D1-2-3 radiotherapy | Experimental | 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. Receives: Radiation: D1-2-3 radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local control of brain metastases at 6 months
Local control at 6 months per brain metastasis evaluated with magnetic resonance imaging (MRI)
Measured: at 6 months
Secondary outcomes (13)
Local control of brain metastases at 12, 18 and 24 months
Local control at 6 months per brain metastasis evaluated with magnetic resonance imaging (MRI).
Measured: at 12, 18 and 24 months
Cerebral control at 12, 18 and 24 months
Cerebral control is defined as the assessment of the control of the entire cerebral parenchyma, including the treated site(s) evaluated with magnetic resonance imaging (MRI).
Measured: at 12, 18 and 24 months
Overall survival
The time from the date of randomization to the date of death, whatever the cause. Patients alive at the time of analysis will be censored on the date of last contact.
Measured: From the date of randomization until the date of death from any cause, loss to follow-up, or 24 months, whichever occurs first
Progression-free survival
Time between the date of randomization and the date of first progression of the irradiated site (or one of the sites irradiated in the event of irradiation of several sites) or the date of death. Patients alive without progression will be censored on the last news date.
Measured: According to local practices until the date of first documented progression or the date of death from any cause or until 24 months, whichever occurs first
Patient Quality of life
Assessment of all dimensions of EORTC QLG Core Questionnaire (EORTC QLQ-C30). Difference on specific symptom scales (from 1 = " not at all " to 4 = " very much ", or from 1 = " really bad " to 7 = " excellent ")
Measured: Before radiotherapy, then at 3, 6, 12, 18 and 24 months from randomization
Patient Quality of life
Assessment of difference on specific symptom scales of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BN20 brain tumour module questionnaire (from 1 = " not at all " to 4 = " very much).
Measured: Before radiotherapy, then at 3, 6, 12, 18 and 24 months from randomization
Risk of leptomeningeal dissemination
Local or diffuse leptomeningeal disease or positive cerebrospinal fluid examination for malignant cells based on MRI findings
Measured: according to local practices until death from any cause or lost to follow-up or until 24 months, whichever came first
Radionecrosis-free survival
The time from the date of randomization to the date of detection of radionecrosis
Measured: according to local practices until death from any cause or lost to follow-up or until 24 months, whichever came first
Patient Safety
Incidence of treatment-related adverse events (TRAEs) graded according to CTCAE v5.0 criteria and deaths
Measured: From the date of randomization until the date of death from any cause, loss to follow-up, or 24 months, whichever occurs first
Patient Safety according to Patient Reported Outcome
Incidence of treatment-related adverse events (TRAEs) according to patient's declaration
Measured: From the date of randomization until the date of death from any cause, loss to follow-up, or 24 months, whichever occurs first
Cognitive decline assessment
Evaluation of neurological function by neuropsychological evaluation, centered on global deficiencies with the Montreal Cognitive Assessment (MoCA). It allows assessment of attention, concentration, executive functions, memory, language, visuoconstructive abilities, abstraction, calculation, and orientation. Maximum score = 30. A score below 26 is considered abnormal.
Measured: At baseline (before radiotherapy), then at 3, 6 and 12 months from randomization
Cognitive decline assessment
Evaluation of neurological function by neuropsychological evaluation, centered on cognitive complaints with the Functional Assessment of Cancer Therapy - Cognitive Function (Fact-Cog) self-questionnaire. It allows assessment of Perceived Cognitive Impairments (from 0 = " never " to 4 = " several times a day "), Comments from Others (from 0 = " never " to 4 = " several times a day "), Perceived Cognitive Abilities (from 0 = " not at all " to 4 = " very much "), Impact on Quality of Life (from 0 = " not at all " to 4 = " very much ")
Measured: at baseline (before radiotherapy), then at 3, 6 and 12 months from randomization
Cognitive decline assessment
Evaluation of neurological function by neuropsychological evaluation. Evaluations centered on information processing speed (Computerized Speed Cognitive Test - CSCT).
Measured: at baseline (before radiotherapy), then at 3, 6 and 12 months from randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2025
- Study startOct 2025 (estimated)
- Primary completionOct 2028 (estimated)
- Study completionApr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 264 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Paul Strauss
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07167134
- Sponsor's protocol ID
- 2021-014
- Acronym
- SISMIC
- Status last verified
- Sep 2025
- First submitted
- 21 Aug 2025
- Last updated
- 11 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evolution of Hypofractionated Stereotactic Irradiation for Radio-Resistant Brain Metastases From D1-3-5 to D1-2-3
- ClinicalTrials.gov ID
- NCT07167134
- Acronym / sponsor ID
- SISMIC / 2021-014
- Conditions
- Brain Metastases
- Keywords
- hypofractionated stereotactic radiotherapy, treatment duration
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 264 participants (estimated)
- Lead sponsor
- Centre Paul StraussUniversity, hospital or other
- Study start
- Oct 2025 (estimated)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Apr 2030 (estimated)
- First posted
- 11 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D1-3-5 radiotherapy | Active comparator | Radiation: D1-3-5 radiotherapyThe 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. |
| D1-2-3 radiotherapy | Experimental | Radiation: D1-2-3 radiotherapyThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D1-3-5 radiotherapy23.1 Gray (Gy) delivered in 3 fractions of 7.7 Gy at D1, D3, and D5 | Radiation | D1-3-5 radiotherapy |
| D1-2-3 radiotherapy23.1 Gray (Gy) delivered in 3 fractions of 7.7 Gy at D1, D2, and D3 | Radiation | D1-2-3 radiotherapy |
Primary outcome
Local control of brain metastases at 6 months
Time frame: at 6 months
Local control at 6 months per brain metastasis evaluated with magnetic resonance imaging (MRI)
13 secondary outcomes
Local control of brain metastases at 12, 18 and 24 months
Time frame: at 12, 18 and 24 months
Cerebral control at 12, 18 and 24 months
Time frame: at 12, 18 and 24 months
Overall survival
Time frame: From the date of randomization until the date of death from any cause, loss to follow-up, or 24 months, whichever occurs first
Progression-free survival
Time frame: According to local practices until the date of first documented progression or the date of death from any cause or until 24 months, whichever occurs first
Patient Quality of life
Time frame: Before radiotherapy, then at 3, 6, 12, 18 and 24 months from randomization
Patient Quality of life
Time frame: Before radiotherapy, then at 3, 6, 12, 18 and 24 months from randomization
Risk of leptomeningeal dissemination
Time frame: according to local practices until death from any cause or lost to follow-up or until 24 months, whichever came first
Radionecrosis-free survival
Time frame: according to local practices until death from any cause or lost to follow-up or until 24 months, whichever came first
Patient Safety
Time frame: From the date of randomization until the date of death from any cause, loss to follow-up, or 24 months, whichever occurs first
Patient Safety according to Patient Reported Outcome
Time frame: From the date of randomization until the date of death from any cause, loss to follow-up, or 24 months, whichever occurs first
Cognitive decline assessment
Time frame: At baseline (before radiotherapy), then at 3, 6 and 12 months from randomization
Cognitive decline assessment
Time frame: at baseline (before radiotherapy), then at 3, 6 and 12 months from randomization
Cognitive decline assessment
Time frame: at baseline (before radiotherapy), then at 3, 6 and 12 months from randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing D1-3-5 radiotherapy and D1-2-3 radiotherapy in people with Brain Metastases, run by Centre Paul Strauss at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anne ANTHONY ((0)388252413 ext. 33, promotion-rc@icans.eu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local control of brain metastases at 6 months (time frame: at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2025.