Avoiding brain radiation when systemic therapy already targets brain metastases

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase 2 pilot pragmatic trial investigates the feasibility of omitting radiation therapy in adults with brain metastases who show an intracranial response to systemic treatment, including immunotherapy, targeted therapy, or chemotherapy. The study enrolls 45 participants in two cohorts: 30 NSCLC patients receiving immunotherapy and 15 patients with brain metastases from other solid tumors. All participants have at least one brain lesion not planned for radiation or surgery and begin systemic therapy expected to cross the blood-brain barrier. Participants receive a repeat brain MRI 4–8 weeks after starting systemic therapy; if lesions are stable or shrinking, radiation is avoided and patients are surveilled, otherwise standard radiation may be given at the physician’s discretion. Primary goal is to determine 6-month radiation therapy–free survival in NSCLC patients by PD-L1 status; secondary aims include intracranial progression-free survival, overall survival, radiation necrosis rate, and quality of life.

Why it matters

Who can join: the full rules

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)

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Where it's running

• University of Vermont Medical Center
  Burlington, Vermont, United States Recruiting

Study contacts

• Study coordinator: Christopher Anker, MD
• Email: chris.anker@uvmhealth.org
• Phone: 1 802 656 2021

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.