Avoiding Radiation Therapy Due to Intracranial Response to Chemotherapy, Targeted Therapy and/or Immuno-ONcology Therapy for Brain Metastases: Pilot Pragmatic Trial

NCT06974370 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: STUDY00003613/UVMCC2502
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Brain Metastases, Adult; Brain Metastases From Non-small Cell Lung Cancer (NSCLC)

Keywords

Brain Metastases; Radiation Therapy; NSCLC; Quality of Life; FACT-Br; NANO Scale; Pragmatic Trial

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• 6-month RTFS

  6 months from baseline brain MRI

Study Arms (1)

Systemic Therapy With Surveillance for Brain Metastases

EXPERIMENTAL

Participants with brain metastases from solid tumors will receive standard-of-care systemic therapy expected to have intracranial activity, such as immunotherapy, targeted therapy, or anti-HER2 agents. A re-evaluation brain MRI will be performed 4-8 weeks after starting therapy. If lesions are stable or responding, patients will continue on systemic therapy with MRI surveillance every 3 months. Radiation therapy may be administered only if progression is observed. All participants are managed according to this pathway, regardless of primary tumor type.

Radiation: Active Surveillance

Interventions

Active Surveillance RADIATION

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.

Systemic Therapy With Surveillance for Brain Metastases

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Vermont Medical Center: lead

Study Sites (1)

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Randall Holcombe, MD, MBA

  University of Vermont Cancer Center

  STUDY DIRECTOR

Central Study Contacts

Christopher Anker, MD

CONTACT

1 802 656 2021; chris.anker@uvmhealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigayor

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 15, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)