This phase II trial tests how well biologically guided radiation therapy (BgRT) and stereotactic body radiation therapy (SBRT) with osimertinib works for the treatment of EGFR positive non-small cell lung carcinoma that has spread from where it first started (primary site) to a limited number of anatomic sites (oligoprogressive). BgRT is radiation that uses specialized imaging to during treatment to target the active tumor and direct radiation to tumors in order to kill and shrink tumor cells. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Osimertinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called EGFR that signals cancer cells to multiply. This helps slow or stop the spread of tumor cells. Giving BgRT with SBRT and osimertinib may kill more tumor cells in patients with oligoprogressive EGFR positive non-small cell lung carcinoma.
Documented informed consent of the participant and/or legally authorized representative
Assent, when appropriate, will be obtained per institutional guidelines
Age: >= 18 years
Eastern Cooperative Oncology Group (ECOG) =< 2
Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy (6 weeks for nitrosoureas or mitomycin C). Exceptions to this exclusion are brain radiation (2 weeks) and osimertinib
Strong CYP3A4 inducers/ inhibitors within 14 days prior to day 1 of protocol therapy
Patients receiving class 1A or class III antiarrhythmic agents within 14 days prior to day 1 of protocol therapy
Drugs known to prolong the corrected QT (QTc) interval
Single group
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT or PET/CT scan
Osimertinib
DrugGiven PO
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Stereotactic Body Radiation Therapy
RadiationUndergo BgRT/SBRT
Survey Administration
Other interventionAncillary study
Percent of patients on planned protocol treatment
Patient counts and percentages will be provided.
Rate of all grades and grade >= 3 adverse events at least possibly related to study therapy
As measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Observed toxicities will be summarized, for all patients in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
Overall survival
Will be estimated using the product-limit method of Kaplan-Meier. Two-sided 95% confidence intervals will be computed.
Change in quality of life (QOL)
As measured by Functional Assessment of Cancer Therapy-General (FACT-G) v4. Repeated QOL assessments will be tabulated and graphically displayed to describe the changes of QOL outcomes over time.
Change in fludeoxyglucose (FDG) uptake
As measured by metabolic tumor volume and total lesion glycolysis at each fraction. Will be analyzed using independent student's t-test to compare normal variables and non-parametric tests including Wilcoxon's signed-rank test for paired data will be used to compare non-normally distributed variables. Repeated measures analysis of variance (ANOVA) will be used to test for differences at more than one time point. Correlation between metabolic tumor volume, total lesion glycolysis and circulating tumor deoxyribonucleic acid (ctDNA) and time to treatment failure (as described above) as well as overall survival will be explored using univariate and multivariate Cox regression.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
