Consolidative Stereotactic Radiosurgery for the Treatment of Brain Metastases in Melanoma and Solid Tumor Cancer Patients, EXCLAIM Trial
This phase II trial studies whether consolidative stereotactic radiosurgery (cSRS) works to control central nervous system (CNS) disease in patients with melanoma or solid tumor cancer that has spread from where it first started (primary site) to the brain (brain metastases [BM]) and to learn if SRS can be used to treat all BM rather than only treating the BM that are getting worse in patients whose disease gets worse after systemic therapy. SRS is a type of treatment that delivers radiation to BM with the intention of killing them completely. Consolidative means that SRS is performed after initial treatment with systemic therapy. Progression directed SRS (pdSRS) delivers SRS only to BM that are getting worse. Giving cSRS and/or pdSRS after systemic therapy may work better at treating BM in melanoma and solid tumor cancer patients.
Inclusion Criteria
- 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
- Subjects must have signed and dated an institutional review board (IRB)/independent ethics committee (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 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
- Eastern Cooperative Oncology Group (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
Exclusion Criteria
- 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 (e.g., osimertinib, brigatinib, alectinib, or lorlatinib)
- Subjects previously treated with whole-brain radiotherapy (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
- 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 Digital Imaging and Communications in Medicine (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)
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06649058.
Locations matching your search criteria
United States
Texas
Houston
PRIMARY OBJECTIVES:
I. To assess whether cSRS improves CNS progression-free survival (CNS-PFS) in patients with BM who have a partial response (PR) or stable disease (SD) with upfront systemic therapy. (Randomization 1)
II. To assess whether SRS to all BM not in complete response (CR) (cSRS + pdSRS) versus only progressing lesions (pdSRS) improves CNS-PFS in patients with CNS progression on upfront systemic therapy. (Randomization 2)
SECONDARY OBJECTIVES:
I. To report the rate and degree of response of BM to systemic therapy by specific regimen and histology.
II. 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).
III. To evaluate rates of leptomeningeal disease (LMD) in all patients managed with upfront systemic therapy and differences in LMD rates between various downstream radiation therapy options (omission, cSRS, pdSRS, etc).
IV. To evaluate neurocognitive changes in patients treated with upfront systemic therapy for BM and differences in these changes between various downstream radiation therapy options (omission, cSRS, pdSRS, etc).
V. 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:
I. To correlate imaging biomarkers with outcomes of BM treated with systemic therapy.
II. To correlate volumetric assessment of lesion response to conventional assessment by modified Response Evaluation Criteria in Solid Tumors (mRECIST) 1.1.
III. To explore machine learning (ML) as a tool to predict outcomes of BM treatment based on disease specific, clinical, and lesion specific features.
IV. To explore the association of circulating bioanalytes with up front systemic therapy for BM and subsequent downstream management strategies (i.e. cSRS).
OUTLINE:
STUDY SYSTEMIC THERAPY (SST): Patients receive CNS-active systemic therapy per the treating medical oncologist's plan on study in the absence of disease progression or unacceptable toxicity. At about 6 weeks after starting CNS-active systemic therapy, patients undergo disease evaluation with magnetic resonance imaging (MRI). Patients may continue to receive CNS-active systemic therapy at the discretion of the treating medical oncologist. Patients with CR are observed with ongoing standard of care MRI on study.
RANDOMIZATION 1: Patients with SD or PR after 6 weeks of SST are randomized to 1 of 2 arms.
ARM I: Patients undergo cSRS over 1-5 doses on study in the absence of disease progression or unacceptable toxicity.
ARM II: Patients undergo ongoing observation throughout the study.
RANDOMIZATION 2: At the time of CNS progressive disease, patients are randomized to 1 of 2 arms.
ARM III: Patients undergo pdSRS over 1-5 doses on study in the absence of disease progression or unacceptable toxicity.
ARM IV: Patients undergo pdSRS plus cSRS over 1-5 doses on study in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MRI throughout the study and may optionally undergo blood sample collection throughout the study.
After completion of study treatment, patients are followed up at weeks 10, 20, 30, 40, and 50, every 12 weeks for year 1, and then every 18 weeks for year 2.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorThomas Hendrix Beckham
- Primary ID2024-1383
- Secondary IDsNCI-2024-08780
- ClinicalTrials.gov IDNCT06649058