RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2025-05-01

Study Completion:2030-09-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06649058

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age ≥ 18 years. 2. 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. 3. Life expectancy \> 6 months as estimated by BM-MDT. 4. BM-MDT agreement that the planned systemic therapy regimen may provide intracranial benefit (SD, PR, or CR in the CNS). 5. 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. 6. The patient's BM are amenable to SRS as initial local therapy as determined by BM-MDT. 7. 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. 8. Histologically confirmed metastatic cancer with at least one measurable metastasis in the brain (≥ 5 mm). 9. 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. 10. Prior SRS and prior excision of BM is permitted if other measurable non irradiated lesions as described in #9 remain. 11. 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. 12. 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. 13. ECOG performance status ≤ 1. 14. Documented agreement by the patient's primary medical oncologist with the appropriateness of planned SST regimen. 15. 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.	1. History of known leptomeningeal involvement (radiographic or cytological). 2. Small cell lung cancer, lymphoma, or leukemia histology. 3. 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). 4. Subjects previously treated with WBRT. 5. 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. 6. Prior disease progression on one or more of the agents comprising SST. 7. Exposure to one or more agents comprising SST within the last 30 days. 8. Prior unacceptable toxicity during treatment with one or more agents comprising SST. 9. 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. 10. 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. 11. 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. 12. Patient weight \>450 pounds. 13. 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. 14. Patient unable to receive a brain MRI (implanted metal devices or foreign bodies) or MRI contrast. 15. Any BM with a significant hemorrhagic component (defined as MRI T1 intrinsic hyperintensity comprising ≥ 25% of maximal lesion diameter).

Inclusion Criteria

Exclusion Criteria

1. Age ≥ 18 years.
2. 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.
3. Life expectancy \> 6 months as estimated by BM-MDT.
4. BM-MDT agreement that the planned systemic therapy regimen may provide intracranial benefit (SD, PR, or CR in the CNS).
5. 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.
6. The patient's BM are amenable to SRS as initial local therapy as determined by BM-MDT.
7. 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.
8. Histologically confirmed metastatic cancer with at least one measurable metastasis in the brain (≥ 5 mm).
9. 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.
10. Prior SRS and prior excision of BM is permitted if other measurable non irradiated lesions as described in #9 remain.
11. 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.
12. 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.
13. ECOG performance status ≤ 1.
14. Documented agreement by the patient's primary medical oncologist with the appropriateness of planned SST regimen.
15. 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.

1. History of known leptomeningeal involvement (radiographic or cytological).
2. Small cell lung cancer, lymphoma, or leukemia histology.
3. 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).
4. Subjects previously treated with WBRT.
5. 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.
6. Prior disease progression on one or more of the agents comprising SST.
7. Exposure to one or more agents comprising SST within the last 30 days.
8. Prior unacceptable toxicity during treatment with one or more agents comprising SST.
9. 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.
10. 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.
11. 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.
12. Patient weight \>450 pounds.
13. 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.
14. Patient unable to receive a brain MRI (implanted metal devices or foreign bodies) or MRI contrast.
15. Any BM with a significant hemorrhagic component (defined as MRI T1 intrinsic hyperintensity comprising ≥ 25% of maximal lesion diameter).

Contacts and Locations

Study Contact

Thomas H Bekham, MD,PHD

CONTACT

713-825-3169

thbeckham@mdanderson.org

Principal Investigator

Thomas H Beckham, MD,PHD

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Thomas H Beckham, MD,PHD, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-05-01

Study Completion Date2030-09-30

Study Record Updates

Study Start Date2025-05-01

Study Completion Date2030-09-30

Terms related to this study

Additional Relevant MeSH Terms

Brain Metastases