Non-small cell lung cancer MedDRA version: 14.1 Level: LLT Classification code 10025051 Term: Lung cancer non-small cell stage II System Organ Class: 100000004864
Conditions
Interventions
Product Name: Afatinib(Tomtovok)
Product Code: BIBW 2992
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: N-[4-[(3-Chloro-4-fluorophenyl)ami
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
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 (T1-2, N0). b. Stage II (T1-2, N1 or T3, N0). The number of participants with predominatly squamous histology eligible to enter the study will be capped at twenty. 4. Measurable disease by contrast-enhanced CT scan: a. The primary tumour must have a diameter on CT imaging of at least 8mm. b. The primary tumour must have an SUVmax on FDG-PET of at least 3.0. 5. ECOG PS 0 – 1. 6. Eligible for complete surgical resection, defined as the appropriate pulmonary parenchymal resection including lobectomy, bi-lobectomy, sleeve lobectomy, or pneumonectomy. 7. Adequate baseline haematopoietic, hepatic and renal function, defined as follows: a. Absolute neutrophil count (ANC) = 1.5 x 109/L. b. Platelet count =100 x 109/L. c. Bilirubin = 1.5 x ULN. d. ALT or AST = 3 x ULN. e. Creatinine = 1.5 x ULN. 8. Ability to take and absorb oral medications. 9. Female patients of childbearing potential (i.e. pre-menopausal females, females who have been menopausal for =65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
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 NSCLC. 4. Any prior or concurrent radiotherapy for NSCLC. 5. Any prior treatment with any 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: d. Uncontrolled hypertension. e. Congestive heart disease NYHA Classification Grade 3. f. 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. Superior vena cava syndrome.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The principal research question is whether a reduction in the amount of energy the cancer uses can be seen when a short course of afatinib is given to early stage lung cancer patients before surgery?; Secondary Objective: Secondary objectives 1. To see if a reduction in tumour volume can be measured by CT imaging after the patients have been taking afatinib for fifteen days. 2. To assess the safety and tolerability of giving afatinib before lung surgery. Exploratory Objectives 1. To look for genetic mutations (not inherited but acquired since birth) that could be causing cancers to grow, such as those for EGFR and ALK genes. 2. To determine how much afatinib gets in to cancer tissue when given as a tablet. 3. To measure the effect inside cancer cells in response to afatinib by looking at changes to signal proteins inside cells when afatinib is taken. 4. To see if it will be feasible to offer tailored adjuvant targeted therapies such as afatinib to NSCLC patients in a larger Phase III clinical trial. ;Primary end point(s): The primary endpoint will assess whether a mean reduction in 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 (+2 if necessary)of therapy with oral afatinib.;Timepoint(s) of evaluation of this end point: The individual PET/CT images will be analysed on an ongoing basis during the study, This will be overseen by the 'Core Laboratory'. The final evaluation of the primary endpoint will be preformed following completion of participation in the study of 59 evaluable patients. This evaluation is expected to take approximately six months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To determine the reduction in tumour size on day fifteen 18F-PET/CT imaging assessed by volumetric CT measurement. 2. To assess safety and tolerability of preoperative afatinib. 3. To assess the feasibility of offering tailored adjuvant targeted therapies to NSCLC patients in Phase III clinical trial context. ; Timepoint(s) of evaluation of this end point: 1. It is anticipated that analysis of volumetric CT assessments will be completed within six months of completion of the study. 2. Formal safety and tolerability reviews will be preformed after 10 and 30 consecutive patients have been recruited to the study. Further reviews will take place as necessary at the request of the Data Monitoring and Ethics Committee who will meet at six monthly intervals. A final toxicity and tolerability analysis will be preformed upon completion of the study. 3. The feasibility of performing a Phase III trial in this context will be assessed upon completion of the study. | — |
Countries
United Kingdom
Contacts
Public ContactDr Clive Mulatero
University of Leeds
Outcome results
None listed