This phase II trial studies how well osimertinib works in treating participants with stage I-IIIA Epithelial Growth Factor Receptor (EGFR) -mutant non-small cell lung cancer before surgery. Osimertinib may stop the growth of tumor cells by blocking mutant EGFR signaling in cancer cells.
Name: Osimertinib
Name: Therapeutic Conventional Surgery
Description: Tumors that exhibit =< 10% viable tumor will meet the criteria for a major pathological response. MPR rate will be determined in patients who receive at least one dose of study drug and become ineligible for surgery either because of disease progression or adverse event will be deemed not to have achieved MPR. The major pathological response rate will be reported with 95% confidence intervals.
Measure: Major pathological response rate (MPR) Time: Up to 1 yearDescription: The frequency and percentages of patients with a best overall response rate of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and by investigator's assessment will be determined from the time of treatment until surgery. The frequency and percentages of patients with a best ORR of CR, PR, SD, or PD will be determined. The ORR will be reported with 95% confidence intervals.
Measure: Objective Response Rate (ORR) Time: Up to 70 daysDescription: DFS will be calculated as 1+ the number of days from date of surgical resection to documented radiographic relapse/progression or death due to any cause over a period of 60 months. The Kaplan-Meier analysis will be used to calculate the median DFS with 95% confidence interval.
Measure: Mean Disease-free survival (DFS) Time: Up to 5 yearsDescription: DFS will be calculated as 1+ the number of days from date of surgical resection to documented radiographic relapse/progression or death due to any cause over a period of 60 months. The 5-year DFS rate will be calculated as the percentage of patients who are disease free at 5 years. This will be calculated using the Kaplan-Meier method
Measure: Disease-free survival rate (DFS) Time: Up to 5 yearsDescription: 5-year OS rate will be calculated using the Kaplan-Meier method . OS will be defined as the 1+ the number of days from surgical resection to death due to any cause over a period of 60 months. The Kaplan-Meier analysis will be used to calculate the median OS with 95% confidence interval.
Measure: Overall survival (OS) Time: Up to 5 yearsDescription: DpR will be defined as the percentage change in tumor burden by RECIST criteria at best response versus baseline imaging. DpR will be summarized using descriptive statistics and correlated with patient outcomes using hazard ratios via the Cox proportional hazards model.
Measure: Depth of response (DpR) Time: Up to 1 yearDescription: The pCR is defined as absence of (0%) viable tumor present histologically in the resected tumor specimen
Measure: Pathologic complete response rate (pCR) Time: Up to 1 yearDescription: Treatment-emergent adverse events will be classified according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Measure: Number of Treatment-emergent adverse events (AEs) Time: Up to 1 yearDescription: Rate of conversion from operable to non-operative will be recorded as rate of patients initially assessed as surgically resectable, who are subsequently unable to undergo surgical resection due to either treatment-related adverse events (AEs) or disease progression.
Measure: Percentage of participants unable to undergo surgical resection Time: Up to 70 daysDescription: Rate of surgical complications occurring prior to the end of treatment visit will be reported
Measure: Percentage of surgical complications Time: Up to 1 yearAllocation: N/A
Single Group Assignment
There are 2 SNPs
Inclusion Criteria: - Males and females >=18 years of age - Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), performed on a biopsy that occurred within the last 90 days - Documented activating EGFR mutation (Exon 19 deletion, T790M, or L858R) on tumor samples by Clinical Laboratory Clinical Laboratory Improvement Amendments (CLIA)-approved test - Positron emission tomography (PET)-computed tomography (CT) within the last 60 days showing radiographic stage I to IIIa lung cancer (mediastinal staging biopsy is allowed but not required) - Brain magnetic resonance imaging (MRI) (or CT if contraindication to MRI) within the last 60 days showing no evidence of metastatic disease - Documentation that the patient is a candidate for surgical resection of their lung cancer by an American Board of Thoracic Surgery certified surgeon - The patient must have a tumor size >=1 centimeter (cm) in its longest diameter. --- T790M --- --- L858R ---
malabsorption syndrome, history of biliary tract disease), including refractory nausea or vomiting, or chronic GI disease which may affect absorption or tolerance to oral medications - History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib - Involvement in the planning and/or conduct of the study (applies to both investigator staff and/or staff at the study site) - Participation in another clinical study with an investigational product during the last 2 months or within five half-lives of the compound, whichever is longer - Uncontrolled medical, psychological, familial, sociological, or geographical conditions that interfere with the patient?s safety, ability to provide informed consent, or ability to comply with the protocol Inclusion Criteria: - Males and females >=18 years of age - Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), performed on a biopsy that occurred within the last 90 days - Documented activating EGFR mutation (Exon 19 deletion, T790M, or L858R) on tumor samples by Clinical Laboratory Clinical Laboratory Improvement Amendments (CLIA)-approved test - Positron emission tomography (PET)-computed tomography (CT) within the last 60 days showing radiographic stage I to IIIa lung cancer (mediastinal staging biopsy is allowed but not required) - Brain magnetic resonance imaging (MRI) (or CT if contraindication to MRI) within the last 60 days showing no evidence of metastatic disease - Documentation that the patient is a candidate for surgical resection of their lung cancer by an American Board of Thoracic Surgery certified surgeon - The patient must have a tumor size >=1 centimeter (cm) in its longest diameter. --- T790M --- --- L858R ---
Inclusion Criteria: - Males and females >=18 years of age - Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), performed on a biopsy that occurred within the last 90 days - Documented activating EGFR mutation (Exon 19 deletion, T790M, or L858R) on tumor samples by Clinical Laboratory Clinical Laboratory Improvement Amendments (CLIA)-approved test - Positron emission tomography (PET)-computed tomography (CT) within the last 60 days showing radiographic stage I to IIIa lung cancer (mediastinal staging biopsy is allowed but not required) - Brain magnetic resonance imaging (MRI) (or CT if contraindication to MRI) within the last 60 days showing no evidence of metastatic disease - Documentation that the patient is a candidate for surgical resection of their lung cancer by an American Board of Thoracic Surgery certified surgeon - The patient must have a tumor size >=1 centimeter (cm) in its longest diameter. --- T790M ---
malabsorption syndrome, history of biliary tract disease), including refractory nausea or vomiting, or chronic GI disease which may affect absorption or tolerance to oral medications - History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib - Involvement in the planning and/or conduct of the study (applies to both investigator staff and/or staff at the study site) - Participation in another clinical study with an investigational product during the last 2 months or within five half-lives of the compound, whichever is longer - Uncontrolled medical, psychological, familial, sociological, or geographical conditions that interfere with the patient?s safety, ability to provide informed consent, or ability to comply with the protocol Inclusion Criteria: - Males and females >=18 years of age - Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), performed on a biopsy that occurred within the last 90 days - Documented activating EGFR mutation (Exon 19 deletion, T790M, or L858R) on tumor samples by Clinical Laboratory Clinical Laboratory Improvement Amendments (CLIA)-approved test - Positron emission tomography (PET)-computed tomography (CT) within the last 60 days showing radiographic stage I to IIIa lung cancer (mediastinal staging biopsy is allowed but not required) - Brain magnetic resonance imaging (MRI) (or CT if contraindication to MRI) within the last 60 days showing no evidence of metastatic disease - Documentation that the patient is a candidate for surgical resection of their lung cancer by an American Board of Thoracic Surgery certified surgeon - The patient must have a tumor size >=1 centimeter (cm) in its longest diameter. --- T790M ---