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

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University

Criteria

Inclusion Criteria:

• Patients must have 1 to 15 newly diagnosed brain metastases, ≤3 cm in the largest dimension, with at least one metastasis measuring ≥0.5 cm.

• Primary tumor histology must be one confirmed as one of the following:

• Squamous NSCLC

• Adenocarcinoma NSCLC

• Not otherwise specified NSCLC

• Patient must be able and willing to undergo a thin cut MRI at Duke, which is required for study entry.

• 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.

• Prothrombin and Partial Thromboplastin Times ≤1.2 x normal

• Neutrophil count ≥1000

• Hemoglobin ≥9 g/dl

• Platelet count ≥100,000/µl

• Creatinine ≤1.2 x normal range.

Exclusion Criteria:

• Patients on the equivalent of >2 mg of dexamethasone daily ≤ 7 days before receiving study treatment

• Patients who have previously receive 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 assuming an interval >6 months has passed from the completion of that therapy.

• Patients with leptomeningeal disease. However, patients with discrete dural-based lesions may be eligible.

• Females who are pregnant or breast-feeding.

• Patients with an impending, life-threatening cerebral hemorrhage or herniation, based on the assessment from a brain MRI of the study neurosurgeons or their designate.

• 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 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 and adequately treated basal cell or squamous cell carcinoma of the skin

• Patients with a known history of hypersensitivity to the physician's choice of immune checkpoint inhibitor, or any components of the inhibitor.

• Patients who have any contraindications to immunotherapy.

• Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months.

• History and/or confirmed pneumonitis, or extensive bilateral lung disease on high resolution/spiral CT scan.