SRS Timing With Immune Checkpoint Inhibition in Patients With Untreated Brain Metastases From Non-small Cell Lung Cancer

Trial details

Who runs it

Duke University

Trial code

NCT04650490

Record updated

2 March 2023

Original description

This trial is a randomized, 2-arm, phase II study to determine the effect, if any, of the timing of stereotactic radiosurgery (SRS) relative to immune checkpoint inhibitor (IO) therapy in patients with non-small cell lung cancer (NSCLC) that has spread (metastasized) to the brain.Read full original descriptionShow less

A Randomized, Phase II Trial of SRS Timing With Immune Checkpoint Inhibition in Patients With Untreated Brain Metastases From Non-small Cell Lung Cancer

This trial is a randomized, 2-arm, phase II study to determine the effect, if any, of the timing of stereotactic radiosurgery (SRS) relative to immune checkpoint inhibitor (IO) therapy in patients with non-small cell lung cancer (NSCLC) that has spread (metastasized) to the brain.

Inclusion: Patients must have 1 to 15 newly diagnosed brain metastases, ≤5 cm in the largest dimension, with at least one metastasis measuring ≥0.3 cm; Primary tumor histology must be one confirmed as one of the following:; Squamous NSCLC; Adenocarcinoma NSCLC; Not otherwise specified NSCLC; Patient must have an MRI of the brain within 4 weeks (28 days) of signing the study consent; Patient must be planned for immunotherapy treatment as their next systemic therapy, including monotherapy or in combination with chemotherapy; Patients previously treated with a tyrosine kinase inhibitor (TKI) may be eligible, if a second line (or later) immunotherapy regimen is planned; Patients must be asymptomatic or minimally symptomatic, requiring the equivalent of ≤2 mg dexamethasone/day for at least 7 days prior to enrollment; Female and male subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in the Duke Contraception Policy; Age ≥18 years of age at the time of entry into the study; Karnofsky Performance Score (KPS) ≥70.

Exclusion: Patients on the equivalent of >2 mg of dexamethasone (or prednisone/steroid equivalent) daily ≤ 7 days before receiving study treatment; Patients who have previously received whole brain radiation therapy (WBRT); Patients must not have ever received immunotherapy in the stage IV setting. Prior immune therapy as part of treatment for stage I-III disease is allowed after an interval of >6 months has passed from the completion of that therapy; Patients with leptomeningeal carcinomatosis. However, patients with discrete dural-based lesions may be eligible at the discretion of the treating radiation oncologist; Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used; Patients with prior, unrelated malignancy requiring current active treatment in the last 3 years with the exception of cervical carcinoma in situ, prostate cancer at stage I-III and adequately treated basal cell or squamous cell carcinoma of the skin; Patients who have any contraindications to immunotherapy; Patients with an impending, life-threatening cerebral hemorrhage or herniation, based on the assessment from a brain MRI of the study neurosurgeons or their designee; Patients with severe, active co-morbidity, defined as follows:; Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C); Patients with known immunosuppressive disease or known uncontrolled human immunodeficiency virus infection; Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4); Patients with a known history of hypersensitivity to the physician's choice of immune checkpoint inhibitor, or any components of the inhibitor; Patients with active autoimmune disease requiring systemic immunomodulatory treatment, including steroid of >10 mg prednisone daily or equivalent, within the past 3 months; Females who are pregnant or breastfeeding.

ClinicalTrials.gov NCT04650490