First Line Osimertinib for EGFR Mutation-positive Non-Small Cell Lung Cancer in Real World Chinese Setting

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

A Prospective, National, Multi-centric, Non-interventional Study of First Line Osimertinib in Chinese Patients With Locally Advanced/Metastatic，EGFR Mutation-positive NSCLC in Real World Setting

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04391283
• Other study ID #: Osimertinib-RWE-01
• Status: Active, not recruiting
• Start date: July 27, 2020
• Est. completion date: December 2024

Study information

• Verified date: February 2023
• Source: First Affiliated Hospital of Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The results of phase III FLAURA study showed a significant PFS benefit for first-line Osimertinib versus standard EGFR-TKIs in patients with EGFR mutation-positive NSCLC, the median PFS was 18.9 months and 10.2 months, respectively. However, only 136 Chinese patients were enrolled in FLAURA study. The objectives of this study are to assess the efficacy and safety of Osimertinib in a real world setting in Chinese patients with locally advanced or metastatic, treatment naïve, epidermal growth factor receptor (EGFR) mutation-positive Non-Small Cell Lung Cancer (NSCLC).

Description:

Total of ~30 study sites are selected for conducting this observational study. Eligible patients will be prospectively and consecutively included. Therefore, the clinical practice in the selected patients group can represent the "real-world" situation in China, and the patient's medical record will be well documented and archived in those hospitals. All data defined in the protocol will be collected during the study and entered in the Electric Data Capture (EDC), being consistent to the patients' medical records.

The most important bias of the study is that patients' characteristics will affect the treatment duration, efficacy and safety, such as, higher proportion of patients with WHO PS 2~3 enroll in the study will result in shorter TTD, poorer effectiveness and higher toxicities than expected. The ~30 sites are not randomly selected and potential selection bias exists. To minimize enrolment bias, the patients who are eligible and consent to participate in the current study will be enrolled consecutively as per protocol and without personal preference from investigators.

The self-selection bias may exit for the willingness and non-willingness participants. We'll try our best to discuss with the non-willingness participants to make sure the consistency/comparative between the willingness and non-willingness participants.

There could be a certain percentage of patients who would lost to follow up, it is unavoidable in clinical study, and is more common in real world study. We can minimize the bias by selecting the hospitals with normative and high-quality clinical practice, trying to collect the reason of lost to follow up and enhancing patient management during the follow up. The above bias is acceptable as this is a "real-world" study. Only descriptive analysis will be performed for the primary, secondary and exploratory objectives. No statistical comparisons between subgroups will be done.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: December 2024
• Est. primary completion date: April 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Ability to provide informed consent, complete all study assessments and have complete medical record;

• Histologically or cytologically documented locally advanced, metastatic NSCLC, which are not amenable to curative surgery or radiotherapy;

• With confirmation of the presence of the EGFR mutation.

• Patients must be treatment- naïve for locally advanced or metastatic NSCLC.

• Age = 18 years

• Patients who plan to receive Osimertinib monotherapy as the initial first line treatment based on physician's medical judgement.

Exclusion Criteria:

• Patients who will be or were involved in any other interventional anti-tumour clinical studies for locally advanced/metastatic NSCLC currently or previously

• Any concomitant condition evaluated by physicians which is not suitable for Osimertinib treatment.

• Patients who have received the first dose of Osimertinib before the signature of ICF won't be allowed to enroll in.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Osimertinib
The recommended dose is 80 mg osimertinib once a day until disease progression or unacceptable toxicity according to the prescription information and clinical practice. It can be taken with or without food at the same time each day.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of College of Medicine Zhejiang University	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
First Affiliated Hospital of Zhejiang University	AstraZeneca

Country where clinical trial is conducted

China, 

References & Publications (10)

Arcila ME, Oxnard GR, Nafa K, Riely GJ, Solomon SB, Zakowski MF, Kris MG, Pao W, Miller VA, Ladanyi M. Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay. Clin Cancer Res. 2011 Mar 1;17(5):1169-80. doi: 10.1158/1078-0432.CCR-10-2277. Epub 2011 Jan 19. — View Citation

Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, Crino L, Satouchi M, Chu Q, Hida T, Han JY, Juan O, Dunphy F, Nishio M, Kang JH, Majem M, Mann H, Cantarini M, Ghiorghiu S, Mitsudomi T. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1643-1652. doi: 10.1016/S1470-2045(16)30508-3. Epub 2016 Oct 14. — View Citation

Jenkins S, Yang JC, Janne PA, Thress KS, Yu K, Hodge R, Weston S, Dearden S, Patel S, Cantarini M, Shepherd FA. EGFR Mutation Analysis for Prospective Patient Selection in Two Phase II Registration Studies of Osimertinib. J Thorac Oncol. 2017 Aug;12(8):1247-1256. doi: 10.1016/j.jtho.2017.05.002. Epub 2017 May 17. — View Citation

John T, Akamatsu H, Delmonte A, Su WC, Lee JS, Chang GC, Huang X, Jenkins S, Wu YL. EGFR mutation analysis for prospective patient selection in AURA3 phase III trial of osimertinib versus platinum-pemetrexed in patients with EGFR T790M-positive advanced non-small-cell lung cancer. Lung Cancer. 2018 Dec;126:133-138. doi: 10.1016/j.lungcan.2018.10.027. Epub 2018 Nov 1. — View Citation

Liu Y, Sun L, Xiong ZC, Sun X, Zhang SL, Ma JT, Han CB. Meta-analysis of the impact of de novo and acquired EGFR T790M mutations on the prognosis of patients with non-small cell lung cancer receiving EGFR-TKIs. Onco Targets Ther. 2017 Apr 24;10:2267-2279. doi: 10.2147/OTT.S133082. eCollection 2017. — View Citation

Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS Response to Osimertinib Versus Standard Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients With Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Aug 28:JCO2018783118. doi: 10.1200/JCO.2018.78.3118. Online ahead of print. — View Citation

Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, Heeroma K, Itoh Y, Cornelio G, Yang PC. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 2014 Feb;9(2):154-62. doi: 10.1097/JTO.0000000000000033. — View Citation

Su KY, Chen HY, Li KC, Kuo ML, Yang JC, Chan WK, Ho BC, Chang GC, Shih JY, Yu SL, Yang PC. Pretreatment epidermal growth factor receptor (EGFR) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer. J Clin Oncol. 2012 Feb 1;30(4):433-40. doi: 10.1200/JCO.2011.38.3224. Epub 2012 Jan 3. Erratum In: J Clin Oncol. 2015 Jun 20;33(18):2124. — View Citation

Zheng R, Zeng H, Zhang S, Chen W. Estimates of cancer incidence and mortality in China, 2013. Chin J Cancer. 2017 Aug 17;36(1):66. doi: 10.1186/s40880-017-0234-3. — View Citation

Zhou C. Lung cancer molecular epidemiology in China: recent trends. Transl Lung Cancer Res. 2014 Oct;3(5):270-9. doi: 10.3978/j.issn.2218-6751.2014.09.01. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to discontinuation (TTD)	Time to discontinuation (TTD), is defined as the time from the date of first dose of Osimertinib in this study until the date of Osimertinib discontinuation for any reason including disease progression, treatment toxicity, death or other reason as recorded in CRF. Subjects who are still on treatment at the time of analysis will be censored at the date of last dose received. Lost to follow-up patients will be censored at last documented contact with patient status "on treatment".	from the date of first dose of Osimertinib in this study until the date of Osimertinib discontinuation for any reason including disease progression, treatment toxicity, death or other reason as recorded in CRF, assessed up to 36 months.
Secondary	Progression-free survival (PFS) and Progression-free survival rate (PFS rate)	Progression-free survival (PFS), is defined as the time from the date of first dose of Osimertinib in this study until the date of disease progression as recorded in CRF or death (by any cause in the absence of progression) regardless of whether the subject withdraws from therapy or receives another anti-cancer therapy prior to progression, which usually refer to Response Evaluation Criteria In Solid Tumours (RECIST) in clinical practice. Subjects who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment. If the subject has no evaluable visits after the baseline visit, they will be censored at 0 days unless they die before the planned visit after the baseline visit. Lost to follow-up patients who have not progressed will be censored at last documented contact with patient status "non-progression".; Progression-free survival rate (PFS rate), is defined as the percentage of patients who do not progress on Osimertinib treatment	from the date of first dose of Osimertinib in this study until the date of disease progression, assessed up to 36 months.
Secondary	Objective Response Rate (ORR) and Disease Control Rate (DCR)	Objective Response Rate (ORR), is defined as the percentage of patients with complete response or partial response by investigator assessment as recorded in the CRF, which usually refer to Response Evaluation Criteria In Solid Tumours (RECIST) in clinical practice.; Disease Control Rate (DCR), is defined as the percentage of patients with non-progression by investigator assessment as recorded in the CRF, which usually refer to Response Evaluation Criteria In Solid Tumours (RECIST) in clinical practice.	from the date of first dose of Osimertinib, assessed up to 6 months.
Secondary	Overall survival rate (OS rate)	Defined as the proportion of patients who are still alive at a particular time in the study (eg, 1 year or 2 years). The patient should be contacted 1 week after the termination of the corresponding OS analysis data to determine survival status. Lost to follow-up patients who have not progressed will be censored at last documented contact with patient status "survival".	from the date of first dose of Osimertinib in this study until the death of patients,assessed up to 48 months.
Secondary	de novo T790M mutation rate	The mutation rate of de novo T790M test by high sensitive technique (analyzed by Next Generation Sequencing platform).; de novo T790M	the baseline and at the time of progression, assessed up to 36 months.
Secondary	Adverse events/Serious adverse events	Incidence of Adverse Events (AEs): Nature, incidence, severity and seriousness of adverse events, Incidence of Serious Adverse Events (SAEs), which usually be graded by CTCAE v4.03 based on current clinical practice.	from the date of first dose of Osimertinib in this study assessed up to 36 months.