[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06974370":3,"trial-entities:NCT06974370":95,"trial-summary:NCT06974370":100},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":21,"study_type":29,"primary_purpose":30,"phases":31,"enrollment_info":33,"interventions":36,"primary_outcomes":43,"secondary_outcomes":48,"sex":52,"minimum_age":53,"maximum_age":54,"healthy_volunteers":55,"eligibility_criteria":56,"std_ages":65,"locations":68,"central_contacts":85,"overall_officials":88,"references":93,"see_also_links":94},"NCT06974370","STUDY00003613\u002FUVMCC2502","Avoiding Radiation Therapy Due to Intracranial Response to Chemotherapy, Targeted Therapy and\u002For Immuno-ONcology Therapy for Brain Metastases: Pilot Pragmatic Trial","Avoiding Radiation Therapy Due to Intracranial Response to Chemotherapy, Targeted Therapy and\u002For Immuno-ONcology Therapy for Brain Metastases: Pilot Pragmatic Trial (ACTION-Brain Metastases: Pilot Pragmatic Trial)","RECRUITING","2030-12","2026-05","2026-05-26","2025-06-05","University of Vermont Medical Center","OTHER",true,"This pilot pragmatic trial evaluates the feasibility of avoiding radiation therapy in patients with brain metastases who demonstrate an intracranial response to systemic therapy-including immunotherapy, targeted therapy, and\u002For chemotherapy. The study will prospectively enroll 45 patients, divided into two cohorts: 30 with non-small cell lung cancer (NSCLC) receiving immunotherapy, and 15 with brain metastases from other solid tumors. Eligible participants must have at least one brain metastasis not planned for radiation or surgery and must be initiating or planning to initiate a systemic therapy regimen expected to penetrate the blood-brain barrier and achieve intracranial activity.\n\nAll patients will undergo a re-evaluation brain MRI 4-8 weeks after initiating systemic therapy. If lesions are stable or regressing, patients will continue surveillance without radiation. If progression is noted, standard-of-care radiation may be administered at the discretion of the treating physician. The primary objective is to assess 6-month radiation therapy-free survival (RTFS) in NSCLC patients based on PD-L1 expression status. Secondary endpoints include intracranial progression-free survival, overall survival, radiation necrosis rate, and quality of life. This study seeks to inform future trial design and identify patients who may safely avoid brain radiation.","This pilot pragmatic trial evaluates the feasibility of avoiding radiation therapy in patients with brain metastases who demonstrate an intracranial response to systemic therapy-including immunotherapy, targeted therapy, and\u002For chemotherapy. The study will prospectively enroll 45 patients, divided into two cohorts: 30 with non-small cell lung cancer (NSCLC) receiving immunotherapy, and 15 with brain metastases from other solid tumors. Eligible participants must have at least one brain metastasis not planned for radiation or surgery and must be initiating or planning to initiate a systemic therapy regimen expected to penetrate the blood-brain barrier and achieve intracranial activity.\n\nAll patients will undergo a re-evaluation brain MRI 4-8 weeks after initiating systemic therapy. If lesions are stable or regressing, patients will continue surveillance without radiation. If progression is noted, standard-of-care radiation may be administered at the discretion of the treating physician. The primary objective is to assess 6-month radiation therapy-free survival (RTFS) in NSCLC patients based on PD-L1 expression status. Secondary endpoints include intracranial progression-free survival, overall survival, radiation necrosis rate, and quality of life. This study seeks to inform future trial design and identify patients who may safely avoid brain radiation.\n\nDetailed Description Brain metastases are the most common tumors of the central nervous system. Historically, treatment has included surgical resection followed by whole-brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) to prevent recurrence. While effective at achieving local control, radiation therapy-particularly WBRT-carries a significant risk of cognitive decline and radiation necrosis, especially in patients with longer life expectancies.\n\nRecent advances in systemic therapy-including immune checkpoint inhibitors, tyrosine kinase inhibitors, and other targeted agents-have demonstrated meaningful intracranial activity, especially in NSCLC, the most common source of brain metastases. Despite these advances, little prospective data exists on the safety and efficacy of deferring radiation therapy in patients responding to systemic treatment.\n\nThis pilot study aims to assess the feasibility of delaying or omitting brain radiation therapy in patients whose brain metastases respond to systemic therapy. It is a prospective, single-institution study enrolling 45 participants across two cohorts: 30 NSCLC patients receiving immunotherapy and 15 patients with brain metastases from other cancer types. Eligible patients must be initiating systemic therapy with agents expected to cross the blood-brain barrier and have at least one brain metastasis not planned for surgical resection or radiation therapy.\n\nPatients will undergo a re-evaluation MRI 4-8 weeks after starting systemic therapy. If metastases are stable or regressing, radiation will be deferred and the patient will enter a structured surveillance protocol with MRIs every 3 months for up to 2 years. If progression is observed, patients may receive radiation therapy per standard of care.\n\nThe primary objective is to determine the variability in 6-month RT-free survival (RTFS) in NSCLC patients with brain metastases based on PD-L1 expression.\n\nSecondary objectives include:\n\nAssessing 6-month RTFS in other histologies\n\nMeasuring local and distant intracranial progression-free survival\n\nEvaluating intracranial objective response rate using iRANO criteria\n\nDetermining the number of metastases avoiding radiation\n\nMeasuring overall survival, disease-specific survival, and radiation necrosis rate\n\nEvaluating quality of life using FACT-Br and neurologic function via the NANO scale\n\nThe study is exploratory and descriptive, with outcomes expected to inform the design of future cooperative group trials. It also complements ongoing trials like NRG-BN013 by evaluating outcomes in a population managed initially without radiation.",[19,20],"Brain Metastases, Adult","Brain Metastases From Non-small Cell Lung Cancer (NSCLC)",[22,23,24,25,26,27,28],"Brain Metastases","Radiation Therapy","NSCLC","Quality of Life","FACT-Br","NANO Scale","Pragmatic Trial","INTERVENTIONAL","TREATMENT",[32],"PHASE2",{"count":34,"type":35},45,"ESTIMATED",[37],{"type":38,"name":39,"description":40,"armGroupLabels":41},"RADIATION","Active Surveillance","Following systemic therapy, participants will undergo active surveillance with brain MRI every 3 months. Radiation therapy will only be initiated if disease progression is observed on imaging, at the discretion of the treating physician.",[42],"Systemic Therapy With Surveillance for Brain Metastases",[44],{"measure":45,"description":46,"timeFrame":47},"6-Month Radiation Therapy-Free Survival (RTFS) by PD-L1 Status in NSCLC Patients with Brain Metastases","To determine variability in 6-month RT-free survival (RTFS) in Non-Small Cell Lung Carcinoma (NSCLC) patients with brain metastases depending on PDL-1 status receiving systemic therapy including immunotherapy","6 months from baseline brain MRI",[49],{"measure":50,"description":51,"timeFrame":47},"6-month RTFS","To determine 6-month RTFS in patients with brain metastases for histologies other than NSCLC receiving systemic therapy expected to have intracranial activity and NSCLC patients receiving systemic therapy other than immunotherapy expected to have intracranial activity","ALL","18 Years",null,false,{"inclusion":57,"exclusion":63,"raw_text":64},[58,59,60,61,62],"Brain penetrant targeted therapies (e.g. tyrosine kinase inhibitors, multikinase inhibitors, EGFR inhibitor, ALK inhibitor, BRAF\u002FMEK inhibitor)","Checkpoint inhibitor immunotherapy (e.g. PDL-1 inhibitors, PD1 inhibitors, CTLA-4 inhibitors)","HER2 antibody-drug conjugate (e.g. TDM1, TDX-D)","Anti-Hormone therapies for Breast Cancer","Cytotoxic chemotherapy alone may be started initially, but with plan for immunotherapy or eligible targeted therapy noted above before the re-evaluation MRI head",[],"Inclusion Criteria:\n\nPathologically (histologically or cytologically) proven diagnosis of a solid tumor malignancies within 5 years prior to registration. If the original histologic proof of malignancy is greater than 5 years, then more recent pathologic confirmation (e.g., from a systemic site or brain metastasis) or unequivocal imaging confirmation of extracranial metastatic disease (e.g. CT of the chest\u002Fabdomen\u002Fpelvis, PET\u002FCT, etc.) is required. These scans are considered standard-of-care (SOC) and will not be ordered for research purposes.\n\nInitiation or planning for initiation of systemic therapy to include one or more of the following categories expected to cause an intracranial response:\n\n* Brain penetrant targeted therapies (e.g. tyrosine kinase inhibitors, multikinase inhibitors, EGFR inhibitor, ALK inhibitor, BRAF\u002FMEK inhibitor)\n* Checkpoint inhibitor immunotherapy (e.g. PDL-1 inhibitors, PD1 inhibitors, CTLA-4 inhibitors)\n* HER2 antibody-drug conjugate (e.g. TDM1, TDX-D)\n* Anti-Hormone therapies for Breast Cancer\n* Cytotoxic chemotherapy alone may be started initially, but with plan for immunotherapy or eligible targeted therapy noted above before the re-evaluation MRI head\n\nAt least 1 brain metastasis that not planned for radiation therapy or surgery.\n\nAll brain metastases not planned for resection much be ≤3 cm, with no minimum size required.\n\nSystemic therapy has started within 4 weeks of MRI brain showing new or progressive disease or plan to start systemic therapy within 4 weeks of MRI brain showing new or progressive disease.\n\nAbility to obtain MRI head scans with contrast. All MRI head scans must have slice thickness ≤1.5 mm.\n\nAge ≥ 18 years\n\nKPS \\>60\n\nAbility to understand and the willingness to sign a written informed consent.\n\nExclusion Criteria:\n\nNo use of the planned new systemic therapy meeting 2.1.2 criteria to address brain metastases within the last 6 months.\n\nPrior radiotherapy to the active brain metastases (partial or whole brain irradiation, or prophylactic cranial irradiation \\[PCI\\])\n\nPatients pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. Negative urine pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal.\n\nSerious medical comorbidities that in the opinion of the investigator would prevent participation in this study.\n\nKnown leptomeningeal disease (LMD)\n\n\\-",[66,67],"ADULT","OLDER_ADULT",[69],{"facility":13,"status":8,"city":70,"state":71,"zip":72,"country":73,"contacts":74,"geoPoint":82},"Burlington","Vermont","05401","United States",[75,80],{"name":76,"role":77,"phone":78,"email":79},"Christopher Anker, MD","CONTACT","802-656-2021","chris.anker@uvmhealth.org",{"name":76,"role":81},"PRINCIPAL_INVESTIGATOR",{"lat":83,"lon":84},44.47588,-73.21207,[86],{"name":76,"role":77,"phone":87,"email":79},"1 802 656 2021",[89],{"name":90,"affiliation":91,"role":92},"Randall Holcombe, MD, MBA","University of Vermont Cancer Center","STUDY_DIRECTOR",[],[],{"nct_id":4,"conditions":96,"biomarkers":99},[97,98],"Lung Non-Small Cell Carcinoma","Solid Neoplasm",[],{"nct_id":4,"found":15,"summary":101,"prompt_version":111},{"design":102,"status":103,"heading":104,"summary":105,"follow_up":106,"word_count":107,"commitments":108,"compensation":109,"drugs_mentioned":110},"This is a pilot study with 45 participants, divided into two groups based on their cancer type. It is an interventional study, meaning participants will receive a specific treatment plan.","completed","Avoiding Radiation for Brain Metastases with Systemic Therapy","This study is looking at whether some patients with brain metastases (cancer that has spread to the brain) can avoid radiation therapy if their tumors respond well to other treatments like chemotherapy, targeted therapy, or immunotherapy. It will include 45 adults, mostly those with non-small cell lung cancer (NSCLC) and some with other solid tumors. You would receive your usual systemic therapy, and doctors would monitor your brain metastases with MRI scans. If your tumors are stable or shrinking, you might not need radiation. The main goal is to see how many NSCLC patients can avoid radiation for at least 6 months, especially depending on their PD-L1 status (a protein on cancer cells).","The primary outcome is measured at 6 months from your baseline brain MRI.",113,"You would undergo brain MRI scans every 3 months after starting systemic therapy. Radiation therapy would only be given if your disease progresses.","Not stated in the trial record.",[],"v2"]