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Trial registered on ANZCTR


Registration number
ACTRN12617000985381
Ethics application status
Approved
Date submitted
4/07/2017
Date registered
10/07/2017
Date last updated
10/07/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Blood based testing in treatment monitoring for EGFR-mutated Non-Small Cell Lung Cancer
Scientific title
Longitudinal follow up study to assess utility of blood based testing using circulating tumour cells (CTC) and circulating tumour DNA (ctDNA) in treatment monitoring for patients with advanced EGFR-mutated Non-small cell lung cancer (NSCLC)
Secondary ID [1] 292313 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic EGFR mutated Lung cancer
 303860 0
Condition category
Condition code
Cancer 303218 303218 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Blood samples collected for CTC and CtDNA isolation before patients start treatment with EGFR inhibitor (Gefitinib 250mg orally once daily or Erlotinib 150mg orally once daily), blood samples were also collected at month 1, 3, 6, 12 and at disease progression.
CTC will be enumerated and individually picked for mutational analyses. CtDNA will be extracted from plasma at all the timepoints for mutational analyses.
Treatment with EGFR inhibitor will be continued until disease progression or unacceptable toxicities.
Intervention code [1] 298490 0
Diagnosis / Prognosis
Comparator / control treatment
Tissue biopsy taken before patients start treatment with EGFR inhibitor if this is available
Control group
Active

Outcomes
Primary outcome [1] 302595 0
Response rate to EGFR inhibitor
Objective response rate (ORR) is defined as the proportion of patients with a documented complete response, partial response (CR + PR) based on iRECIST criteria.
Timepoint [1] 302595 0
3 months into treatment
Secondary outcome [1] 336465 0
Progression Free Survival (PFS)
PFS is defined as the time from the first dose of gefitinib/erlotinib 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.
Timepoint [1] 336465 0
one year after the recruitment of the final patient to the study
Secondary outcome [2] 336727 0
Overall survival (OS)
OS defined as the time from the first dose of gefitinib/erlotinib 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.
Timepoint [2] 336727 0
one year after the recruitment of the final patient to the study
Secondary outcome [3] 336728 0
Concordance rate
The concordance between blood based testing with tissue biopsy will be evaluated by comparing mutation detection in CTC/ctDNA in the blood with pre treatment tissue biopsy. An activating mutation will be considered concordant if this is detected both in the blood and in the tissue biopsy.
Timepoint [3] 336728 0
pre treatment

Eligibility
Key inclusion criteria
Above 18 years old
New diagnosis of metastatic EGFR mutated NSCLC and will be started on first generation EGFR inhibitors
Compliance with blood collection at pre-specified time points
Compliance with EGFR inhibitors
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Early stage disease
Non-compliance to treatment or blood collection

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis
Diagnostic accuracy of blood based testing with CTC and ctDNA will be compared with tissue biopsies in terms of concordance rate, sensitivity and specificity.
Descriptive statistics will be used for patient demographics, disease and treatment information.
Survival data will be analysed using Kaplan Meier analysis.
Non-parametric statistics will be utilized. A Mann-Whitney U and Kruskal-
Wallis test will be used for testing the difference between two and greater than two independent continuous variables respectively. A Spearman correlation will be performed when testing the strength of association between two continuous variables. Lastly, to test the strength of the association between two categorical variables, a Chi-Square was utilized. If the sample size is small, a Fisher’s Exact test will be used. A p-value <0.05 was
considered statistically significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/02/2016
Date of last participant enrolment
Anticipated
29/12/2017
Actual
Date of last data collection
Anticipated
31/12/2018
Actual
Sample size
Target
25
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 16542 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 296855 0
Hospital
Name [1] 296855 0
Medical Oncology Department, Liverpool Hospital
Country [1] 296855 0
Australia
Primary sponsor type
Hospital
Name
Medical Oncology Department, Liverpool Hospital
Address
Elizabeth Street, Liverpool, NSW 2170
Country
Australia
Secondary sponsor category [1] 295861 0
University
Name [1] 295861 0
Western Sydney University
Address [1] 295861 0
School of Medicine
30, Western Sydney University,
Narellan Road & Gilchrist Drive, Campbelltown NSW 2560
Country [1] 295861 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298083 0
South Western Sydney Local Health District Ethics committee
Ethics committee address [1] 298083 0
Liverpool Hospital
Elizabeth Street
NSW 2170
Ethics committee country [1] 298083 0
Australia
Date submitted for ethics approval [1] 298083 0
23/09/2015
Approval date [1] 298083 0
18/11/2015
Ethics approval number [1] 298083 0
HREC/13/LPOOL/158

Summary
Brief summary
This study aims to evaluate the utility of blood based testing ('liquid biopsy') in the management of patients with Epidermal Growth Factor Receptor mutated (EGFR+) non-small cell lung cancer (NSCLC)

Who is it for?
You may be eligible to join this study if you are aged 18 years or above and have metastatic EGFR+ NSCLC and will be starting treatment with EGFR inhibitors.

Study details
We will perform a prospective follow up study to investigate if liquid biopsy could be used to monitor the treatment response and detect treatment resistance in EGFR+ NSCLC patients. Participants will be required to have blood collected (3 tubes of 9ml blood sample each time) before they start treatment, 1 month into treatment, 3 months into treatment and 6 months into treatment. We will be analysing cancer cells and cancer DNA which may be found in the blood (ie. circulating cancer cells/CTC and circulating tumour DNA/ctDNA).

It is hoped that this study will add to the currently limited knowledge on whether we could use CTC/ctDNA to predict the effectiveness of a treatment, as well as clinical outcomes for patients. This study will also hopefully answer the question of whether common mutations and novel mutations causing treatment resistance could be detected in liquid biopsy, and therefore could replace the more invasive tissue biopsy in the future to diagnose and monitor treatment response for patients with EGFR+ lung cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75938 0
Dr Pei Ni Ding
Address 75938 0
Ingham Institute for Applied Medical Research
1 Campbell Street
Liverpool, NSW 2170
Country 75938 0
Australia
Phone 75938 0
+610425292277
Fax 75938 0
Email 75938 0
[email protected]
Contact person for public queries
Name 75939 0
Pei Ni Ding
Address 75939 0
Ingham Institute for Applied Medical Research
1 Campbell Street
Liverpool NSW 2170
Country 75939 0
Australia
Phone 75939 0
+61425292277
Fax 75939 0
Email 75939 0
[email protected]
Contact person for scientific queries
Name 75940 0
Pei Ni Ding
Address 75940 0
Ingham Institute for Applied Medical Research
1 Campbell Street
Liverpool NSW 2170
Country 75940 0
Australia
Phone 75940 0
+61425292277
Fax 75940 0
Email 75940 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
SourceTitleYear of PublicationDOI
EmbaseThe predictive and prognostic significance of liquid biopsy in advanced epidermal growth factor receptor-mutated non-small cell lung cancer: A prospective study.2019https://dx.doi.org/10.1016/j.lungcan.2019.06.021
N.B. These documents automatically identified may not have been verified by the study sponsor.