Avoiding Radiation Therapy Due to Intracranial Response to Chemotherapy, Targeted Therapy and/or Immuno-ONcology Therapy for Brain Metastases: Pilot Pragmatic Trial
Recruiting · NCT06974370 · Interventional (participants receive a specific treatment) · Lead sponsor: University of Vermont Medical Center
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
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/or 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. All 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.
Who can take part
Inclusion criteria
- Pathologically (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/abdomen/pelvis, PET/CT, etc.) is required. These scans are considered standard-of-care (SOC) and will not be ordered for research purposes.
- Initiation or planning for initiation of systemic therapy to include one or more of the following categories expected to cause an intracranial response:
- Brain penetrant targeted therapies (e.g. tyrosine kinase inhibitors, multikinase inhibitors, EGFR inhibitor, ALK inhibitor, BRAF/MEK 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
- At least 1 brain metastasis that not planned for radiation therapy or surgery.
- All brain metastases not planned for resection much be ≤3 cm, with no minimum size required.
- Systemic 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.
- Ability to obtain MRI head scans with contrast. All MRI head scans must have slice thickness ≤1.5 mm.
- Age ≥ 18 years
- KPS \>60
- Ability to understand and the willingness to sign a written informed consent.
Exclusion criteria
- No use of the planned new systemic therapy meeting 2.1.2 criteria to address brain metastases within the last 6 months.
- Prior radiotherapy to the active brain metastases (partial or whole brain irradiation, or prophylactic cranial irradiation \[PCI\])
- Patients 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.
- Serious medical comorbidities that in the opinion of the investigator would prevent participation in this study.
- Known leptomeningeal disease (LMD)
Where it is running
1 location listed across 1 US state.
- University of Vermont Medical Center - Burlington, Vermont, United States