Phase II Trial of the Addition of Biologically Guided Radiation Therapy (BgRT) and Stereotactic Body Radiation Therapy (SBRT) to Tyrosine Kinase Inhibitor in Oligoprogressive Oncogenic Positive Non-Small Cell Lung Carcinoma
Summary
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.
Detailed description
PRIMARY OBJECTIVE: I. To estimate the percent of patients receiving benefit at 6 months from the addition of BgRT/SBRT to first line osimertinib in EGFR positive non-small cell lung cancer (NSCLC) patients with oligoprogressive disease (disease control rate \[DCR\]). SECONDARY OBJECTIVES: I. To evaluate the tolerability of adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. II. To estimate the overall survival when adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. III. To describe the effect on quality of life (QOL) when adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. IV. To describe the effect on quantified fludeoxyglucose F-18 (FDG) uptake changes when adding BgRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. V. To estimate local and distant control rates when adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. VI. To estimate the extracranial progression free survival (PFS) when adding SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. VII. To estimate the time to treatment failure (TTF) when adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. VII. To estimate percentage of patients needing salvage BgRT/SBRT when adding SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. EXPLORATORY OBJECTIVES: I. To identify potential predictors of outcome when adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. II. To describe the changes in circulating tumor deoxyribonucleic acid (ctDNA) levels when adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease. OUTLINE: Patients continue to receive osimertinib orally (PO) daily (QD) in the absence of unacceptable toxicity. Patients undergo BgRT/SBRT every other day for 5 treatments. Patients then continue to receive osimertinib and are monitored via imaging. If additional progression is found, patients may receive additional BgRT/SBRT therapy. Treatment continues in the absence of \> 5 sites of progression, unacceptable toxicity, or the stopping of osimertinib for more than 4 weeks. Patients undergo computed tomography (CT) scan or positron emission tomography(PET)/CT scan and blood sample collection throughout the study. After completion of initial radiation therapy, patients follow up at 1 week, 3 months, 6 months and 12 months and then for an additional year.
Arms & interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureComputed Tomography
Undergo CT or PET/CT scan
- DrugOsimertinib
Given PO
- ProcedurePositron Emission Tomography
Undergo PET/CT
- RadiationStereotactic Body Radiation Therapy
Undergo BgRT/SBRT
- OtherSurvey Administration
Ancillary study
Outcome measures
Primary
Percent of patients on planned protocol treatment
Patient counts and percentages will be provided.
Time frame: At 6 months
Secondary
Rate of all grades and grade >= 3 adverse events at least possibly related to study therapy
Time frame: Up to 2 years
Overall survival
Time frame: From the date of study enrollment to the date of death from any cause, up to 2 years
Change in quality of life (QOL)
Time frame: From baseline to 3 months post initial stereotactic body radiation therapy (SBRT)
Change in fludeoxyglucose (FDG) uptake
Time frame: From baseline to completion of SBRT, up to 2 years
Ratio of patients achieving local control and distant control
Time frame: Up to 2 years
First occurrence of disease progression
Time frame: From study entry to first occurrence of disease progression, up to 2 years
Time to treatment failure
Time frame: From study entry to treatment failure, up to 2 years
Ratio of patients needing salvage BgRT/SBRT
Time frame: Up to 1 year
Eligibility criteria
Study locations (2)
City of Hope Medical Center
Duarte, California, 91010
Yale University
New Haven, Connecticut, 06520