Condition category
Cancer
Date applied
15/08/2013
Date assigned
16/08/2013
Last edited
14/08/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Mrs Jenny Boards

ORCID ID

Contact details

Level 6 Bexley Wing
St James' University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
able@leedsth.nhs.uk

Additional identifiers

EudraCT number

2012-004537-16

ClinicalTrials.gov number

Protocol/serial number

14691

Study information

Scientific title

An Open Label Multi-Centre Preoperative Window of Opportunity Study of Afatinib in Stage Ia to IIb Non-Small Cell Lung Cancer

Acronym

ABLE

Study hypothesis

The anticancer effect of afatinib can be observed within fifteen days of starting treatment by Positron Emission Tomography (18F-FDG PET) imaging.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=14691

Ethics approval

Yorkshire and the Humber – Leeds East, 08/01/2013, ref: 12/YH/0539

Study design

Open label non randomised interventional phase II clinical study; Design type: Treatment

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Lung Cancer; Disease: Lung (non-small cell)

Intervention

After giving informed consent patients will undergo a range of screening investigations including blood tests, ECG and a heart scan to ensure that they are eligible to take part.

Some patients will also be asked to undergo another optional biopsy in order to obtain cancer tissue for the research.

All eligible participants will be asked to take a single 50mg tablet of afatinib by mouth once each day until the date of their pre-planned surgery.

After participants have been taking the afatinib tablets for two weeks they will undergo another PET/CT scan to study what effect the afatinib has had upon their cancer. They will also have a chest X-ray and give a blood sample on this date.

The total duration of treatment with afatinib tablets will be at least fifteen days but no longer than 30 days from when each participant starts taking them. They will give another blood sample on the morning of their surgery.

The participants’ contribution to this study will end after they have been reviewed four weeks following their surgery. On this occasion they will give a final related blood sample.

The study team will also collect information about each participant by reviewing notes made at their routine lung cancer related outpatient appointments over the next five years.

Intervention type

Drug

Phase

Phase II

Drug names

Afatinib

Primary outcome measures

The primary endpoint will assess whether a mean reduction in maximal Standardised Uptake Value (SUVmax) of 10% can be observed in the patient group enrolled in the study by 18F-FDG PET imaging after they have received fifteen days of therapy with oral afatinib

Secondary outcome measures

1. The CT volumetric secondary endpoint will assess whether a reduction of > 30% in tumour volume can be observed in the patient group enrolled in the study using the CT component of 18F-FDG PET/CT imaging after they have received fifteen days of therapy with oral afatinib.
2. Toxicity and safety data for each patient will be assessed. Toxicity analyses will be preformed after 10 and 30 consecutive patients have completed afatinib therapy and at the end the study.
3. Feasibility of conducting further ‘Window of Opportunity’ trials in this setting in the UK for the NSCLC cancer population will be assessed through the ability to appropriately identify, approach, consent the target study population in compliance with the study protocol.

Overall trial start date

16/09/2013

Overall trial end date

16/09/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Able to give written informed consent and willing to follow the study protocol
2. Age >= 18 years
3. Histologically confirmed resectable non-small cell lung cancer, meeting one of the following clinical staging criteria:
a. Stage 1A or 1B (T12, N0).
b. Stage II (T12, N1 or T3, N0)
The number of participants with predominantly squamous histology eligible to enter the study will be capped at twenty.
4. Measurable disease by contrast-enhanced CT scan:
4.1. The primary tumour must have a diameter on CT imaging of at least 8mm.
4.2. The primary tumour must have an SUVmax on FDGPET of at least 3.0.
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 – 1.
6. Eligible for complete surgical resection, defined as the appropriate pulmonary parenchymal resection including lobectomy, bilobectomy, sleeve lobectomy, or pneumonectomy.
7. Adequate baseline haematopoietic, hepatic and renal function, defined as follows:
7.1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
7.2. Platelet count ≥100 x 109/L
7.3. Bilirubin ≤ 1.5 x ULN
7.4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3 x ULN
7.5. Creatinine ≤ 1.5 x ULN
8. Ability to take and absorb oral medications.
9. Female patients of childbearing potential (i.e. premenopausal females, females who have been menopausal for < 1 year and not surgically sterilized, or males not surgically sterilized) must provide a negative pregnancy test (urine or serum) ≤ 7 days before study treatment begins and must agree to practice effective contraceptive measures for the duration of study drug therapy and for at least 30 days after completion of study drug therapy.
10. Male participants must agree to use a barrier method of contraception for the duration of the study if sexually active
with a female of childbearing potential and must continue to do so for 30 days after the end of treatment.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 59

Participant exclusion criteria

1. Tumours of mixed histology (combined small cell and non small cell carcinoma), pulmonary carcinoid tumours, or large cell carcinoma with evidence of neuroendocrine features. However non-small cell tumours with mixed adenocarcinoma and squamous cell carcinoma histology are eligible.
2. Patients with preoperative radiological evidence of N2 disease by either PET/CT or CT scan (i.e. radiological evidence of metastasis to ipsilateral mediastinal and subcarinal lymph nodes) that is confirmed as N2 disease histologically/cytologically.
3. Any prior or concurrent systemic chemotherapy for Non-small-cell lung carcinoma (NSCLC).
4. Any prior or concurrent radiotherapy for NSCLC.
5. Any prior treatment with any epidermal growth factor receptor (EGFR) inhibitor.
6. Current treatment with potent P-glycoprotein inhibitors or inducers.
7. Any other concurrent malignancy with the exception of non-melanoma skin cancers.
8. Known pre-existing interstitial lung disease.
9. Significant or recent (within 6 months) acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn’s disease, malabsorption or CTC grade ≥ 2 diarrhoea of any aetiology.
10. History or presence of clinically relevant cardiovascular abnormalities such as:
10.1. Uncontrolled hypertension.
10.2. Congestive heart disease New York Heart Association (NYHA) Classification Grade 3.
10.3. Unstable angina or poorly controlled arrhythmia.
11. Congestive Cardiac failure, with left ventricular ejection fraction of < 50% as measured by echocardiography/Gated SPECT/MUGA imaging.
12. Uncontrolled infection, or any serious illness or organ system dysfunction which in the opinion of the investigator would either compromise participant safety or interfere with the evaluation of the safety of the test drug.
13. Pregnant (positive pregnancy test) or breast feeding women.
14. History of a poorly controlled neurologic or psychiatric condition that, in the Investigator’s opinion, is likely to interfere with the participant’s ability to participate and / or to comply with the requirements of the study.
15. Active hepatitis B infection, active hepatitis C infection or known HIV carrier.
16. Ocular inflammatory or chronic infectious conditions.
17. Poorly controlled diabetes mellitus.
18. Known or suspected active drug or alcohol abuse.
19. Participation in another investigational drug trial whilst on study.
20. Known hypersensitivity to afatinib or to any of the excipients contained in the tablet preparation.
21. Superior vena cava syndrome.

Recruitment start date

16/09/2013

Recruitment end date

16/09/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Level 6 Bexley Wing
Leeds
LS9 7TF
United Kingdom

Sponsor information

Organisation

University of Leeds (UK)

Sponsor details

c/o Faculty Head of Research and Innovation Support
Faculty of Medicine and Health
Worsley Building
Leeds
LS2 9LN
United Kingdom

Sponsor type

University/education

Website

http://www.leeds.ac.uk/

Funders

Funder type

Industry

Funder name

Boehringer Ingelheim Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes