ABLE Trial Afatinib Before Lung surgEry: a study investigating the effect of giving a course of a targeted tablet treatment called afatinib to patients with potentially curable non-small cell lung cancer during the short interval between their diagnosis and the removal of their cancer by surgery
| ISRCTN | ISRCTN16279802 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16279802 |
| EudraCT/CTIS number | 2012-004537-16 |
| Secondary identifying numbers | 14691 |
- Submission date
- 15/08/2013
- Registration date
- 16/08/2013
- Last edited
- 28/05/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Mrs Jenny Boards
Scientific
Scientific
Level 6 Bexley Wing
St James' University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
| able@leedsth.nhs.uk |
Study information
| Study design | Open label non randomised interventional phase II clinical study; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | An open label multi-centre preoperative window of opportunity study of afatinib in stage Ia to IIb non-small cell lung cancer |
| Study acronym | ABLE |
| Study objectives | The anticancer effect of afatinib can be observed within fifteen days of starting treatment by Positron Emission Tomography (18F-FDG PET) imaging. |
| Ethics approval(s) | Yorkshire and the Humber - Leeds East, 08/01/2013, ref: 12/YH/0539 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Afatinib |
| Primary outcome measure | 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 study start date | 16/09/2013 |
| Completion date | 16/09/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | UK Sample Size: 59 |
| Total final enrolment | 7 |
| Key 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 |
| Key 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. Crohns 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 Investigators opinion, is likely to interfere with the participants 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 |
| Date of first enrolment | 16/09/2013 |
| Date of final enrolment | 16/09/2015 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
St James' University Hospital
Leeds
LS9 7TF
United Kingdom
LS9 7TF
United Kingdom
Sponsor information
University of Leeds (UK)
University/education
University/education
c/o Faculty Head of Research and Innovation Support
Faculty of Medicine and Health
Worsley Building
Leeds
LS2 9LN
England
United Kingdom
| Website | http://www.leeds.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/024mrxd33 |
Funders
Funder type
Industry
Boehringer Ingelheim
Private sector organisation / For-profit companies (industry)
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Boehringer Ingelheim Pharmaceuticals, Inc., Boehringer Ingelheim International GmbH, BI, BIPI
- Location
- United States of America
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 28/05/2020 | No | No | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
28/05/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
09/11/2017: No publications found, verifying study status with principal investigator.
