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Report for Clinical Trial NCT03433469

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase II Study to Evaluate Neoadjuvant Osimertinib Therapy in Patients With Surgically Resectable, EGFR-Mutant Non-Small Cell Lung Cancer

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.

NCT03433469 Stage I Non-Small Cell Lung Cancer Stage IA Non-Small Cell Lung Cancer Stage IB Non-Small Cell Lung Cancer Stage II Non-Small Cell Lung Cancer Stage IIA Non-Small Cell Lung Cancer Stage IIB Non-Small Cell Lung Cancer Stage IIIA Non-Small Cell Lung Cancer
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

3 Interventions

Name: Laboratory Biomarker Analysis

Description: Correlative studies
Type: Other
Group Labels: 1

Treatment (osimertinib)

Name: Osimertinib

Description: Given PO (orally)
Type: Drug
Group Labels: 1

Treatment (osimertinib)

Name: Therapeutic Conventional Surgery

Description: Undergo surgery
Type: Procedure
Group Labels: 1

Treatment (osimertinib)


Primary Outcomes

Description: Tumors that exhibit =< 10% viable tumor will meet the criteria for a major pathological response. The major pathological response rate will be reported with 95% confidence intervals.

Measure: Major pathological response rate (MPR) defined as =< 10% viable tumor present histologically in the resected tumor specimen

Time: Up to 1 year

Secondary Outcomes

Description: The Kaplan-Meier analysis will be used to calculate the mean DFS with 95% confidence interval.

Measure: 1 year disease-free survival (DFS)

Time: From date of surgical resection to documented radiographic relapse/progression or death due to any cause, assessed up to 1 year

Description: The Kaplan-Meier analysis will be used to calculate the mean OS with 95% confidence interval.

Measure: 1 year overall survival (OS)

Time: From surgical resection to death due to any cause, assessed up to 1 year

Description: Depth of response 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) defined as the percentage change in tumor burden by RECIST criteria at best response versus baseline imaging

Time: Baseline up to 1 year

Description: 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) will be determined. The ORR will be reported with 95% confidence intervals.

Measure: Objective Response Rate (ORR) determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria by investigator's assessment

Time: From start of treatment until time of surgery

Measure: Pathologic complete response rate (pCR) defined as absence of (0%) viable tumor present histologically in the resected tumor specimen

Time: Up to 1 year

Description: 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: Rate of inability to undergo surgical resection

Time: Up to 1 year

Description: Rate of surgical complications occurring prior to the end of treatment visit will be recorded.

Measure: Rate of surgical complications occurring prior to the end of treatment visit

Time: Up to 1 year

Description: AE terms recorded on the case report forms (CRFs) will be mapped to preferred terms using the Medical Dictionary for Regulatory Activities (MedDRA). Seriousness, severity grade and relationship to study treatment will be assessed by the investigator. Severity grade will be defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Measure: Treatment-emergent adverse events (AEs), laboratory abnormalities and electrocardiogram (ECG) abnormalities

Time: Up to 1 year

Other Outcomes

Description: Rates of adverse pathologic features including rates of positive margins, lymphovascular invasion (LVI), and pathologic upstaging (e.g. by T or N status) as compared to clinical staging based on pre-operative scans, for comparison to historical controls will be recorded.

Measure: Adverse pathologic outcomes

Time: Up to 1 year

Description: Descriptive statistics and graphical methods will be used to analyze the data.

Measure: Changes in circulating tumor deoxyribonucleic acid (ctDNA)

Time: Baseline up to 1 year

Measure: Changes in immune cell infiltration

Time: Baseline up to 1 year

Description: Performance of RNA sequencing and whole exome sequencing analysis on isolated cancer cell populations from pre-treatment tumor biopsy specimens, as well as tumor tissue acquired at the time of surgical resection. Changes of expression levels to baseline will described by calculating z-score

Measure: Calculation of z-score to describe genomic and transcriptional changes within cancer cell populations after treatment

Time: Baseline up to 1 year

Description: Peripheral blood and plasma samples will be stored for the assessment of variant allele frequencies

Measure: Concentration of ctDNA in peripheral blood samples

Time: Up to 1 year

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There are 2 SNPs

SNPs


1 L858R

Inclusion Criteria: - Males and females ≥18 years of age - Histologically or cytologically confirmed non-small cell lung cancer, 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, 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 ---


2 T790M

Inclusion Criteria: - Males and females ≥18 years of age - Histologically or cytologically confirmed non-small cell lung cancer, 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, 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 ---



HPO Nodes


HPO: