Brain MetastasesPhase 2NCT06649058
EXCLAIM: Exploring Combined Local and Systemic Approaches In Brain Metastasis: a Multi-cohort Randomized Phase II Study Evaluating Initial Response to Systemic Therapy and Subsequent Integration of Stereotactic Radiosurgery in Patients With Low-risk Brain Metastases and Central Nervous System-active
A Phase 2 study testing Systemic Therapy and Stereotactic Radiosurgery in people with Brain Metastases, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To learn if consolidative stereotactic radiosurgery (cSRS) can help to control central nervous system (CNS) disease in patients who have brain metastases and have a partial response or stable brain metastases after systemic therapy. 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?
- Systemic Therapy and Stereotactic Radiosurgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 316 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Feb 2025to 30 Sep 2030
- Phase
- Phase 2
- 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.
- Evaluation by a brain metastasis multidisciplinary team (BM-MDT) consisting of a medical oncologist (can be the patient's primary medical oncologist), a radiation oncologist who regularly performs SRS, and a neurosurgeon. This evaluation can take place in clinic or during a multidisciplinary conference.
- Life expectancy > 6 months as estimated by BM-MDT.
- BM-MDT agreement that the planned systemic therapy regimen may provide intracranial benefit (SD, PR, or CR in the CNS).
- BM-MDT agreement that the patient's BM does not require immediate local therapy (surgery and/or radiation therapy); i.e. it is judged to be safe to omit local therapy as initial BM management.
- The patient's BM are amenable to SRS as initial local therapy as determined by BM-MDT.
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- Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
- Histologically confirmed metastatic cancer with at least one measurable metastasis in the brain (≥ 5 mm).
- At least one measurable intracranial target lesion which was not previously treated with SRS. Regrowth in a cavity of previously excised lesion will not qualify as a measurable lesion. Growth or change in a lesion previously irradiated will not qualify as a measurable lesion.
- Prior SRS and prior excision of BM is permitted if other measurable non irradiated lesions as described in #9 remain.
- The resection cavity of excised BM must have received appropriate radiation therapy (pre or post operative SRS, brachytherapy) or have been observed for >6 months after resection without evidence of local cavity recurrence.
- Subjects must be free of neurologic signs and symptoms related to metastatic brain lesions either without systemic corticosteroids or requiring ≤ 2 mg dexamethasone daily for symptom resolution.
- ECOG performance status ≤ 1.
- Documented agreement by the patient's primary medical oncologist with the appropriateness of planned SST regimen.
- This study will allow non-English speaking subjects to be enrolled. Verbal Translation Preparative Sheet (VTPS) will be used if a translated consent form is not available in the subject's language. The consent form will be translated into the language of the subject after 2 or more occurrences. This will apply to any MD Anderson patient.
Who cannot join
- History of known leptomeningeal involvement (radiographic or cytological).
- Small cell lung cancer, lymphoma, or leukemia histology.
- Non-small cell lung cancer histology with targetable oncogenic driver mutation with planned initiation of highly CNS active targeted therapy (eg osimertinib, brigatinib, alectinib, or lorlatinib).
- Subjects previously treated with WBRT.
- Any intact BM size > 3 cm. After surgical excision and appropriate radiation therapy to the cavity, patients may enroll if additional eligible lesions are present.
- Prior disease progression on one or more of the agents comprising SST.
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- Exposure to one or more agents comprising SST within the last 30 days.
- Prior unacceptable toxicity during treatment with one or more agents comprising SST.
- Subjects with a major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled.
- History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Note: The time requirement does not apply to participants who underwent successful treatment of superficial bladder cancer, in situ cervical cancer, ductal carcinoma in situ, or other in-situ cancers. Subjects with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.
- Skin Cancer Exclusion: Please note that localized cutaneous basal cell carcinoma and squamous cell carcinoma is not an exclusion criterion regardless of treatment status. Biopsy proven metastatic disease from these histologies is an exclusion criterion if this constitutes a second cancer.
- Patient weight >450 pounds.
- Patient had prior SRS to any intracranial lesion <15mm from a metastasis on the screening MRI. Prior MRIs and DICOMs will be used to make this determination.
- Patient unable to receive a brain MRI (implanted metal devices or foreign bodies) or MRI contrast.
- Any BM with a significant hemorrhagic component (defined as MRI T1 intrinsic hyperintensity comprising ≥ 25% of maximal lesion diameter).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Thomas H Beckham, MD,PHD, 713-825-3169, thbeckham@mdanderson.org
Thomas H Beckham, MD,PHD
About this study
Official title: EXCLAIM: Exploring Combined Local and Systemic Approaches In Brain Metastasis: a Multi-cohort Randomized Phase II Study Evaluating Initial Response to Systemic Therapy and Subsequent Integration of Stereotactic Radiosurgery in Patients With Low-risk Brain Metastases and Central Nervous System-active Systemic Therapy Options
To learn if consolidative stereotactic radiosurgery (cSRS) can help to control central nervous system (CNS) disease in patients who have brain metastases and have a partial response or stable brain metastases after systemic therapy.
To learn if using SRS to treat all brain metastases that do not respond to systemic therapy versus treating only metastases that are getting worse can help to control CNS disease in patients whose disease gets worse after systemic therapy.
Read the detailed description
Primary Objectives:
To assess whether cSRS improves CNS progression-free survival (CNS-PFS) in patients with BM who have a PR or SD with upfront systemic therapy.
To assess whether SRS to all BM not in CR (cSRS + pdSRS) versus only progressing lesions (pdSRS) improves CNS-PFS in patients with CNS progression on upfront systemic therapy.
Secondary Objectives:
To report the rate and degree of response of BM to systemic therapy by specific regimen and histology.
To report adverse neurologic events that occur with BM treated with upfront systemic therapy and differences in these events between various downstream radiation therapy options (omission, cSRS, pdSRS, etc).
To evaluate rates of LMD in all patients managed with upfront systemic therapy and differences in LMD rates between various downstream radiation therapy options (omission, cSRS, pdSRS, etc).
To evaluate neurocognitive changes in patients treated with upfront systemic therapy for BMand differences in these changes between various downstream radiation therapy options (omission, cSRS, pdSRS, etc).
To perform inference on overall survival as estimated by the Kaplan-Meier estimator in patients treated with upfront systemic therapy for BM and differences in these changes between various downstream radiation therapy options (omission, cSRS, pdSRS, etc).
Exploratory Objectives:
To correlate imaging biomarkers with outcomes of BM treated with systemic therapy.
To correlate volumetric assessment of lesion response to conventional assessment by mRECIST 1.1.
To explore ML as a tool to predict outcomes of BM treatment based on disease specific, clinical, and lesion specific features.
To explore the association of circulating bioanalytes with up front systemic therapy for BM and subsequent downstream management strategies (i.e. cSRS).
- Conditions
- Brain Metastases
- Being tested
- Systemic Therapy, Stereotactic Radiosurgery
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Systemic TherapyOther
Participants will receive systemic therapy as a standard of care therapeutic option
Stereotactic RadiosurgeryRadiation
Participants will receive systemic therapy as a standard of care therapeutic option
| Study group | Role | What they receive |
|---|---|---|
| cSRS PR or SD | Experimental | Patients with a CR will be observed with ongoing standard of care MRI. Patients with SD or PR will be randomized to receive cSRS or ongoing observation. Receives: Other: Systemic Therapy; Radiation: Stereotactic Radiosurgery |
| a-pdSR CNS PD | Experimental | At the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS. Receives: Other: Systemic Therapy; Radiation: Stereotactic Radiosurgery |
| b-PDC CNS PD | Experimental | At the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS. Receives: Other: Systemic Therapy; Radiation: Stereotactic Radiosurgery |
| SST treated SD or PR patients to receive cSRS/ ongoing observation | Experimental | Patients with a CR will be observed with ongoing standard of care MRI. Patients with SD or PR will be randomized to receive cSRS or ongoing observation. Receives: Other: Systemic Therapy; Radiation: Stereotactic Radiosurgery |
| SST treated PD patients to pdSRS / pdSRS+cSRS | Experimental | At the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS. Receives: Other: Systemic Therapy; Radiation: Stereotactic Radiosurgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Adverse Events (AEs).
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2024
- Study start14 Feb 2025
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 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.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 316 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thomas H Beckham, MD,PHD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06649058
- Sponsor's protocol ID
- 2024-1383
- Other IDs
- NCI-2024-08780
- Status last verified
- Oct 2026
- First submitted
- 17 Oct 2024
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EXCLAIM: Exploring Combined Local and Systemic Approaches In Brain Metastasis: a Multi-cohort Randomized Phase II Study Evaluating Initial Response to Systemic Therapy and Subsequent Integration of Stereotactic Radiosurgery in Patients With Low-risk Brain Metastases and Central Nervous System-active Systemic Therapy Options
- ClinicalTrials.gov ID
- NCT06649058
- Acronym / sponsor ID
- 2024-1383
- Conditions
- Brain Metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 316 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 14 Feb 2025 (actual)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 30 Sep 2030 (estimated)
- First posted
- 18 Oct 2024 (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.
To learn if consolidative stereotactic radiosurgery (cSRS) can help to control central nervous system (CNS) disease in patients who have brain metastases and have a partial response or stable brain metastases after systemic therapy.
To learn if using SRS to treat all brain metastases that do not respond to systemic therapy versus treating only metastases that are getting worse can help to control CNS disease in patients whose disease gets worse after systemic therapy.
Detailed description
Primary Objectives:
To assess whether cSRS improves CNS progression-free survival (CNS-PFS) in patients with BM who have a PR or SD with upfront systemic therapy.
To assess whether SRS to all BM not in CR (cSRS + pdSRS) versus only progressing lesions (pdSRS) improves CNS-PFS in patients with CNS progression on upfront systemic therapy.
Secondary Objectives:
To report the rate and degree of response of BM to systemic therapy by specific regimen and histology.
To report adverse neurologic events that occur with BM treated with upfront systemic therapy and differences in these events between various downstream radiation therapy options (omission, cSRS, pdSRS, etc).
To evaluate rates of LMD in all patients managed with upfront systemic therapy and differences in LMD rates between various downstream radiation therapy options (omission, cSRS, pdSRS, etc).
To evaluate neurocognitive changes in patients treated with upfront systemic therapy for BMand differences in these changes between various downstream radiation therapy options (omission, cSRS, pdSRS, etc).
To perform inference on overall survival as estimated by the Kaplan-Meier estimator in patients treated with upfront systemic therapy for BM and differences in these changes between various downstream radiation therapy options (omission, cSRS, pdSRS, etc).
Exploratory Objectives:
To correlate imaging biomarkers with outcomes of BM treated with systemic therapy.
To correlate volumetric assessment of lesion response to conventional assessment by mRECIST 1.1.
To explore ML as a tool to predict outcomes of BM treatment based on disease specific, clinical, and lesion specific features.
To explore the association of circulating bioanalytes with up front systemic therapy for BM and subsequent downstream management strategies (i.e. cSRS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| cSRS PR or SD | Experimental | Other: Systemic Therapy, Radiation: Stereotactic RadiosurgeryPatients with a CR will be observed with ongoing standard of care MRI. Patients with SD or PR will be randomized to receive cSRS or ongoing observation. |
| a-pdSR CNS PD | Experimental | Other: Systemic Therapy, Radiation: Stereotactic RadiosurgeryAt the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS. |
| b-PDC CNS PD | Experimental | Other: Systemic Therapy, Radiation: Stereotactic RadiosurgeryAt the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS. |
| SST treated SD or PR patients to receive cSRS/ ongoing observation | Experimental | Other: Systemic Therapy, Radiation: Stereotactic RadiosurgeryPatients with a CR will be observed with ongoing standard of care MRI. Patients with SD or PR will be randomized to receive cSRS or ongoing observation. |
| SST treated PD patients to pdSRS / pdSRS+cSRS | Experimental | Other: Systemic Therapy, Radiation: Stereotactic RadiosurgeryAt the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age ≥ 18 years.
- Evaluation by a brain metastasis multidisciplinary team (BM-MDT) consisting of a medical oncologist (can be the patient's primary medical oncologist), a radiation oncologist who regularly performs SRS, and a neurosurgeon. This evaluation can take place in clinic or during a multidisciplinary conference.
- Life expectancy > 6 months as estimated by BM-MDT.
- BM-MDT agreement that the planned systemic therapy regimen may provide intracranial benefit (SD, PR, or CR in the CNS).
- BM-MDT agreement that the patient's BM does not require immediate local therapy (surgery and/or radiation therapy); i.e. it is judged to be safe to omit local therapy as initial BM management.
Key exclusion criteria (15 listed)
- History of known leptomeningeal involvement (radiographic or cytological).
- Small cell lung cancer, lymphoma, or leukemia histology.
- Non-small cell lung cancer histology with targetable oncogenic driver mutation with planned initiation of highly CNS active targeted therapy (eg osimertinib, brigatinib, alectinib, or lorlatinib).
- Subjects previously treated with WBRT.
- Any intact BM size > 3 cm. After surgical excision and appropriate radiation therapy to the cavity, patients may enroll if additional eligible lesions are present.
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 |
|---|---|---|
| Systemic TherapyParticipants will receive systemic therapy as a standard of care therapeutic option | Other | SST treated PD patients to pdSRS / pdSRS+cSRS, SST treated SD or PR patients to receive cSRS/ ongoing observation, a-pdSR CNS PD, b-PDC CNS PD, cSRS PR or SD |
| Stereotactic RadiosurgeryParticipants will receive systemic therapy as a standard of care therapeutic option | Radiation | SST treated PD patients to pdSRS / pdSRS+cSRS, SST treated SD or PR patients to receive cSRS/ ongoing observation, a-pdSR CNS PD, b-PDC CNS PD, cSRS PR or SD |
Primary outcome
Safety and Adverse Events (AEs).
Time frame: Through study completion; an average of 1 year.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
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 6 Oct 2026.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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.
Thomas H Beckham, MD,PHD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Systemic Therapy and Stereotactic Radiosurgery in people with Brain Metastases, run by M.D. Anderson Cancer Center at 1 site in United States.
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 15 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 6 Oct 2026. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Thomas H Bekham, MD,PHD (713-825-3169, thbeckham@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Adverse Events (AEs). (time frame: Through study completion; an average of 1 year.). 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 6 Oct 2026.