Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000993392p
Ethics application status
Not yet submitted
Date submitted
29/06/2017
Date registered
10/07/2017
Date last updated
10/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Clinical Outcome of Epidermal Growth Factor Receptor mutated (EGFR+) Non-small cell lung cancer (NSCLC) patients with first-line tyrosine kinase inhibitors (TKI) resistance on Osimertinib (CONTROL)
Scientific title
Clinical outcome of advanced EGFR-mutated NSCLC patients who developed acquired resistance to first generation EGFR inhibitors with positive plasma T790M treated with osimertinib in NSW, Australia.
Secondary ID [1] 292312 0
None
Universal Trial Number (UTN)
Trial acronym
CONTROL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
metastatic EGFR mutated non small cell lung cancer
 303852 0
Acquired resistance to first line EGFR inhibitor 303853 0
Condition category
Condition code
Cancer 303215 303215 0 0
Lung - Non small cell

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Metastatic EGFR mutated NSCLC patients who developed acquired resistance with a secondary EGFR mutation T790M. These patients were started on osimertinib (80mg daily orally until disease progression/significant toxicities) and clinical outcomes of these patients will be observed (response rate, progression free survival and overall survival). The duration of observation will be a minimum of one year since the start of treatment with osimertinib. Maximum duration of observation will be 3 years from the start of treatment.
Intervention code [1] 298484 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302588 0
Objective response rate (ORR) is defined as the proportion of patients with a documented complete response, partial response (CR + PR) based on iRECIST criteria/investigator defined.
Timepoint [1] 302588 0
3 months into treatment with osimertinib
Secondary outcome [1] 336450 0
Overall survival (OS) is a secondary endpoint of this study.
It is defined as the time from the first dose of Osimertinib to the date of death due to any cause. Patients who are alive at the time of the final analysis or who have become lost to follow-up will be censored at their last known alive date. All patients who meet the eligibility criteria will be included in the analysis of OS. A Kaplan-Meier estimate of proportions of patients alive will be displayed. The 95% confidence intervals for the median OS will be computed using the method of Brookmeyer and Crowley. The effect of potential prognostic factors on survival (ie. RAF) will be assessed using Cox regression model. The Schoenfeld residual plots will be used to check the model assumption for the Cox regression.
Timepoint [1] 336450 0
analysis of OS will be after minimum of one year follow up ie. assessed one year after the last patient commence on osimertinib therapy.
Secondary outcome [2] 336602 0
Progression free survival (PFS) is a secondary endpoint of this study, which is defined as the time from the first dose of Osimertinib to the date of the first documented disease progression (based on investigator-defined progression) or death due to any cause. A patient who stops treatment with study drug and goes on to receive alternative therapy for NSCLC, prior to documentation of disease progression, will be censored on the date alternative therapy began. If a patient has not progressed or received alternative therapy, PFS will be censored on the date of the last disease assessment. All patients will be included in the analysis of PFS. All analyses for OS will be similarly performed for PFS.
Timepoint [2] 336602 0
analysis of PFS will be after minimum of one year follow up ie. assessed one year after the last patient commence on osimertinib therapy.

Eligibility
Key inclusion criteria
Over 18 years old
Metastatic EGFR mutated NSCLC
Developed acquired resistance to first generation EGFR inhibitor
Plasma/Tumour positivity for T790M
Started on Osimertinib in second line/subsequent line setting
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Early lung cancer
Not T790M positive
Not on Osimertinib

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Sample Size: We estimate to have approximately 70 patients for this study. The patients will be stratified based on RAF of T790M (divided into 2 groups: (1) Group 1 = RAF greater than or equal to 10%; (2) Group 2= RAF less than 10%. Based on our preliminary data of 15 patients, 1/3 of the patients will be in group 1 and 2/3 of the patients will be in group 2, giving a 1:2 ratio. Assuming response rate of 70% for group 1 and 30% for group 2, 66 subjects are needed to achieve 80% power using a 2-sided Type 1 error of 5%.
Cox-regression will be used to analysed data for PFS and OS. Fishers exact test will be used to analyse the association between Relative Alleilic frequency of T790M with response rate.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2017
Actual
Date of last participant enrolment
Anticipated
31/12/2017
Actual
Date of last data collection
Anticipated
1/03/2019
Actual
Sample size
Target
66
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 296853 0
Hospital
Name [1] 296853 0
Liverpool Hospital Medical Oncology
Country [1] 296853 0
Australia
Funding source category [2] 296854 0
University
Name [2] 296854 0
Western Sydney University
Country [2] 296854 0
Australia
Primary sponsor type
Hospital
Name
Medical Oncology Department, Liverpool Hospital
Address
Elizabeth Street, Liverpool, NSW 2170
Country
Australia
Secondary sponsor category [1] 295860 0
University
Name [1] 295860 0
Western Sydney University
Address [1] 295860 0
School Of Medicine
30, Western Sydney University, Narellan Road & Gilchrist Drive, Campbelltown NSW 2560
Country [1] 295860 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 298082 0
Liverpool Hospital HREC
Ethics committee address [1] 298082 0
Liverpool Hospital
Elizabeth Street
Liverpool, NSW 2170
Ethics committee country [1] 298082 0
Australia
Date submitted for ethics approval [1] 298082 0
01/08/2017
Approval date [1] 298082 0
Ethics approval number [1] 298082 0

Summary
Brief summary
This study aims to evaluate clinical outcomes of patients with non-small cell lung cancer (NSCLC) with specific clinical and tumour mutation characteristics treated with osimertinib in NSW, Australia.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above and have metastatic EGFR mutated NSCLC with plasma/tumour positivity for T790M, currently taking osimertinib, and were previously treated with first generation EGFR inhibitor (gefitinib/erlotinib).

Study details
We will perform a retrospective analysis of the clinical outcomes in NSCLC patients. We will follow up on your clinical data (first CT scan results and long term outcome from your treatment) and correlate this with the level of T790M mutation shown in your plasma ctDNA.

Participants will not be required to undergo any additional tests beside routine clinical tests requested by their oncologists.

It is hoped that this study will add to the currently limited knowledge on the correlation between T790M mutation load (relative allelic frequency) and clinical outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75934 0
Dr Pei Ni Ding
Address 75934 0
Ingham Institute for Applied Medical Research
1, Campbell Street
Liverpool, NSW 2170
Country 75934 0
Australia
Phone 75934 0
+61425292277
Fax 75934 0
Email 75934 0
[email protected]
Contact person for public queries
Name 75935 0
Dr Pei Ni Ding
Address 75935 0
Ingham Institute for Applied Medical Research
1, Campbell Street
Liverpool, NSW 2170
Country 75935 0
Australia
Phone 75935 0
+61425292277
Fax 75935 0
Email 75935 0
[email protected]
Contact person for scientific queries
Name 75936 0
Dr Pei Ni Ding
Address 75936 0
Ingham Institute for Applied Medical Research
1, Campbell Street
Liverpool, NSW 2170
Country 75936 0
Australia
Phone 75936 0
+61425292277
Fax 75936 0
Email 75936 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.