Osimertinib in Treating Participants With Stage I-IIIA EGFR-mutant Non-small Cell Lung Cancer Before Surgery
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|ClinicalTrials.gov Identifier: NCT03433469|
Recruitment Status : Recruiting
First Posted : February 14, 2018
Last Update Posted : May 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|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||Other: Laboratory Biomarker Analysis Drug: Osimertinib Procedure: Therapeutic Conventional Surgery||Phase 2|
I. To evaluate the efficacy of osimertinib as neoadjuvant therapy in patients with surgically resectable EGFR-mutant non-small cell lung cancer (NSCLC).
I. To evaluate the safety of osimertinib given as neoadjuvant therapy in early stage EGFR-mutant NSCLC participants.
II. To evaluate whether neoadjuvant osimertinib treatment increases the frequency of tumors that are unresectable due to adverse events or disease progression.
III. To evaluate secondary measures of clinical efficacy in early stage EGFR-mutant NSCLC patients treated with osimertinib induction therapy.
I. To evaluate long-term measures of efficacy in patients treated with osimertinib neoadjuvant therapy.
II. To explore tissue and cell-free biomarkers that may be predictive of response or primary resistance to osimertinib neoadjuvant therapy.
Participants receive osimertinib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection of their cancer.
After completion of study treatment, participants are followed up at 30 days then every 3 months for up to 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study to Evaluate Neoadjuvant Osimertinib Therapy in Patients With Surgically Resectable, EGFR-Mutant Non-Small Cell Lung Cancer|
|Actual Study Start Date :||July 31, 2018|
|Estimated Primary Completion Date :||May 31, 2021|
|Estimated Study Completion Date :||May 31, 2022|
Experimental: Treatment (osimertinib)
Participants receive osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection of their cancer.
Other: Laboratory Biomarker Analysis
Given PO (orally)
Procedure: Therapeutic Conventional Surgery
- Major pathological response rate (MPR) defined as =< 10% viable tumor present histologically in the resected tumor specimen [ Time Frame: Up to 1 year ]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.
- 1 year disease-free survival (DFS) [ Time Frame: From date of surgical resection to documented radiographic relapse/progression or death due to any cause, assessed up to 1 year ]The Kaplan-Meier analysis will be used to calculate the mean DFS with 95% confidence interval.
- 1 year overall survival (OS) [ Time Frame: From surgical resection to death due to any cause, assessed up to 1 year ]The Kaplan-Meier analysis will be used to calculate the mean OS with 95% confidence interval.
- Depth of response (DpR) defined as the percentage change in tumor burden by RECIST criteria at best response versus baseline imaging [ Time Frame: Baseline up to 1 year ]Depth of response will be summarized using descriptive statistics and correlated with patient outcomes using hazard ratios via the Cox proportional hazards model.
- Objective Response Rate (ORR) determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria by investigator's assessment [ Time Frame: From start of treatment until time of surgery ]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.
- Pathologic complete response rate (pCR) defined as absence of (0%) viable tumor present histologically in the resected tumor specimen [ Time Frame: Up to 1 year ]
- Rate of inability to undergo surgical resection [ Time Frame: Up to 1 year ]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.
- Rate of surgical complications occurring prior to the end of treatment visit [ Time Frame: Up to 1 year ]Rate of surgical complications occurring prior to the end of treatment visit will be recorded.
- Treatment-emergent adverse events (AEs), laboratory abnormalities and electrocardiogram (ECG) abnormalities [ Time Frame: Up to 1 year ]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.
- Adverse pathologic outcomes [ Time Frame: Up to 1 year ]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.
- Changes in circulating tumor deoxyribonucleic acid (ctDNA) [ Time Frame: Baseline up to 1 year ]Descriptive statistics and graphical methods will be used to analyze the data.
- Changes in immune cell infiltration [ Time Frame: Baseline up to 1 year ]
- Calculation of z-score to describe genomic and transcriptional changes within cancer cell populations after treatment [ Time Frame: Baseline up to 1 year ]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
- Concentration of ctDNA in peripheral blood samples [ Time Frame: Up to 1 year ]Peripheral blood and plasma samples will be stored for the assessment of variant allele frequencies
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03433469
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94115|
|Contact: Collin M. Blakely, M.D. 877-827-3222 email@example.com|
|Principal Investigator: Collin M. Blakely, M.D.|
|United States, Colorado|
|University of Colorado||Not yet recruiting|
|Denver, Colorado, United States, 80217-3364|
|Contact: Robert C. Doebele 303-724-2980 firstname.lastname@example.org|
|Contact: Paula Fisk 720-848-0676 Paula.Fisk@ucdenver.edu|
|Principal Investigator: Robert C. Doebele|
|Principal Investigator:||Collin Blakely||University of California, San Francisco|