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Trial registered on ANZCTR


Trial ID
ACTRN12613001221741
Ethics application status
Approved
Date submitted
19/08/2013
Date registered
6/11/2013
Date last updated
8/11/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
The Effect of Afatinib on the Anti-Tumour Immune Response in Patients with Advanced Non-Small Cell Lung Cancer
Scientific title
The Effect of Afatinib on the Anti-Tumour Immune Response in Patients with Advanced Non-Small Cell Lung Cancer
Secondary ID [1] 283431 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced non-small cell lung cancer 289436 0
Condition category
Condition code
Cancer 289765 289765 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Afatinib (BIBW 2992) 40 mg per day, oral.
The appropriate number of afatinib tablets for 3 - 6 weeks of treatment will be provided to patients to be self administered at home. Patients will be asked to bring remaining trial medication at the end of each dosing period to the investigator site for a compliance check.
Patients remain on afatinib until progression, toxicity, patient wishes or clinician judgement mandate removal from study.
This is not primarily an efficacy study. It is a pilot translational study examining the effect of afatinib on the anti-tumour immune response in patients with advanced NSCLC.
Intervention code [1] 288150 0
Treatment: Drugs
Comparator / control treatment
Not applicable

Control group
Uncontrolled

Outcomes
Primary outcome [1] 289850 0
The Primary Outcome Measure is the numbers and phenotype of the constituents of the immune cell population.
Whole blood is assayed for change in proliferating CD8+ T cells as a proportion of total CD8+ T cells following treatment. Specifically, the primary endpoint will be changes from baseline to week 3 and 6 in the proportion of Ki67+ and ICOS+ CD8+ T cells as a function of total CD8+ T cells.
Timepoint [1] 289850 0
Baseline, Days 21, 42 & Day 28 after last dose of Afatinib
Secondary outcome [1] 303460 0
To correlate immune responses with antitumour response in patients with NSCLC.

Antitumour response is assessed by radiological response using Response Evaluation Criteria in Solid Tumours (RECIST 1.1 assessed on CT).

Timepoint [1] 303460 0
A CT scan will be performed at Baseline, Days 42, 84, then every 12 weeks thereafter until progression, and Day 28 after last dose of Afatinib.
Secondary outcome [2] 305144 0
To correlate immune response with survival outcomes in patients with NSCLC.
Timepoint [2] 305144 0
Baseline to time of death. This information will be sourced from the hospital database.

Eligibility
Key inclusion criteria
1. Patients with a diagnosis of advanced NSCLC (IIIb/IV) with either:
* Documented EGFR mutation and any line of therapy (including first-line), or
* Patients satisfying the Jackman criteria of acquired resistance to an EGFR TKI.
2. ECOG PS 0-2
3. Willingness to undergo study blood tests at SCGH
4. Adequate organ function at baseline
5. Written informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Unable or unwilling to undergo study blood tests at SCGH
2. Concurrent chemotherapy
3. Chemotherapy within 3 weeks of study entry
4. Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom
5. History of clinically significant cardiac disease
6. Known autoimmune disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients are registered to the study following eligibility check. Screening investigations are then performed prior to study treament. There is no treatment allocation procedure as the study is not randomised and all subjects receive study drug.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
N/A
Phase
Not Applicable
Type of endpoint(s)
Pharmacodynamics
Statistical methods / analysis
All statistical analyses will be performed on the group as a whole, with secondary exploratory analyses with participants stratified by EGFR mutation status (known sensitive mutation; unknown mutation or mutation with unknown sensitivity; no mutation or known insensitive mutation).
Objective radiological responses will be reported as proportions of participants and as per RECIST 1.1.
Toxicity will be reported using the CTCAE version 3.0. Median survival and time to progression will be calculated from on-study time using the Kaplan-Meier method.
Translational data will be analysed longitudinally using a linear mixed model, and relationships with survival and toxicity analysed using multivariable analysis.
Change in proliferating CD8+ T cells as a proportion of total CD8+ T cells following treatment is the primary outcome. The standard deviation of change in this variable from day 0 to day 90 in a group of 10 healthy controls has been used for this calculation (SD=1.1). Data from patients undergoing chemotherapy showed a 50% increase in the proportion of proliferating CD8+ T cells 21 days after the start of treatment (from 4% to 6%) (McCoy et al. 2012).
A sample size of 20 patients will be adequate to detect a change in proliferating CD8+ T cells from 4% to 5.5 % with SD=1.1, a =0.05 and beta =0.8 using a linear mixed model.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 1168 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 7015 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 287574 0
Commercial sector/Industry
Name [1] 287574 0
Boehringer Ingelheim Pty Ltd
Address [1] 287574 0
78 Waterloo Rd
North Ryde
NSW 2113
Country [1] 287574 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
Hospital Avenue
Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 286527 0
None
Name [1] 286527 0
Address [1] 286527 0
Country [1] 286527 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289746 0
Sir Charles Gairdner Hospital Human Research Ethics Committee
Ethics committee address [1] 289746 0
A block, Sir Charles Gairdner Hospital
Hospital Ave
Nedlands WA 6009
Ethics committee country [1] 289746 0
Australia
Date submitted for ethics approval [1] 289746 0
22/01/2013
Approval date [1] 289746 0
23/10/2013
Ethics approval number [1] 289746 0
2013-021

Summary
Brief summary
This study is evaluating the effect of Afatinib on the anti-tumour immune response in patients with advanced non-small cell lung cancer.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above and have been diagnosed with advanced non-small cell lung cancer (IIIb/IV). You also need to be willing to undergo study blood tests at Sir Charles Gairdner Hospital in Nedlands, Western Australia.

Study details
All participants in this study will undergo treatment with Afatinib. Afatinib is an oral drug which is known to be effective in treating some types of lung cancer, particularly those with a mutation in EGFR. The purpose of this research study is to determine how Afatinib affects the cells of the immune system during treatment for lung cancer. There is now evidence to suggest that some cancer treatment drugs may help the immune system to attack cancer cells. If this is the case, it might be possible to develop better cancer treatments by combining them with drugs that stimulate the immune system further. However, it is important to understand exactly how different drugs affect the immune system before deciding which combinations might work well together.

Treatment with Afatinib is a once daily tablet, divided into 6 week courses. Treatment will continue while it is of benefit to the patient, and will be stopped for safety reasons or if consent is withdrawn. Research blood samples will be taken at baseline, after 3 weeks and 6 weeks on treatment, and a final one 28 days after last dose of Afatinib. The research bloods will be used to characterise and measure the numbers of different immune cells in the blood, and how well they are reacting against the cancer. Routine blood tests will be required every 6 weeks while on Afatinib to monitor the safety of treatment as is standard for all patients having cancer treatment. Research bloods can be taken with routine bloods at the appropriate time points. A CT scan will be performed at baseline, at 6 weeks and 12 weeks after starting treatment and thereafter at 12-week intervals. A clinic visit is required at baseline, 3 weeks after starting treatment, and then on the first day of each course. Approximately 20 people at Sir Charles Gairdner Hospital only will participate in this study.
Trial website
N/A
Trial related presentations / publications
None to date
Public notes
This is not primarily an efficacy study. It is a pilot translational study examining the effect of afatinib on the anti-tumour immune response in patients with advanced NSCLC. However, the immune response will be correlated with treatment efficacy, as defined by radiological response (RECIST 1.1 assessed on CT), time to progression and overall survival.

Contacts
Principal investigator
Name 40970 0
Prof Anna Nowak
Address 40970 0
Department of Medical Oncology
Comprehensive Cancer Centre
DD block
Sir Charles Gairdner Hospital
Hospital Ave Nedlands WA 6009
Country 40970 0
Australia
Phone 40970 0
+61 8 9346 3333
Fax 40970 0
Email 40970 0
anna.nowak@uwa.edu.au
Contact person for public queries
Name 40971 0
Ms Judy Innes-Rowe
Address 40971 0
Department of Medical Oncology
Comprehensive Cancer Centre
DD block
Sir Charles Gairdner Hospital
Hospital Ave Nedlands WA 6009
Country 40971 0
Australia
Phone 40971 0
+61 8 6383 3000
Fax 40971 0
Email 40971 0
judy.innes-rowe@health.wa.gov.au
Contact person for scientific queries
Name 40972 0
Dr Alistair Cook
Address 40972 0
School of Medicine and Pharmacology
4th FLoor, G block
Sir Charles Gairdner Hospital
Hospital Ave Nedlands WA 6009
Country 40972 0
Australia
Phone 40972 0
+61 8 9346 3488
Fax 40972 0
Email 40972 0
alistair.cook@uwa.edu.au