Health Condition 1: null- Non Small Cell Lung Cancer
Conditions
Interventions
Intervention1: Afatinib: 40 mg, po daily Continuous daily dosing until disease progression
Control Intervention1: Erlotinib: 150 mg, po daily Continuous daily dosing until disease progression
Sponsors
Boehringer Ingelheim India Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1. Diagnosis of advanced stage NSCLC considered to be squamous histology, including mixed histology, in the opinion of the investigator. 2. Completion of at least 4 cycles of platinum-based doublet chemotherapy, with or without additional [non-EGFR] targeted agents, as 1st line treatment of Stage IIIB/IV NSCLC. This includes patients relapsing within 6 months of completing adjuvant/neo-advjuvant/curative -intent chemotherapy/chemoradiotherapy. (Note: these patients are still required to have had the equivalent of 4 cycles of platinumbased doublet chemotherapy) 3. Eligible to receive 2nd line therapy in the opinion of the investigator. Patients who received non-EGFR based therapy for maintenance are eligible. 4. Measurable disease according to RECIST 1.1 (R09-0262). Refer to Appendix 10.1. 5. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (R01-0787). Refer to Appendix 10.2. 6. Availability of tumour tissue material for correlative studies (refer to Section 5.6). Archived tumour tissue is acceptable. 7. Adequate organ function, defined as all of the following: a. LVEF >50% or within institution normal values. b. Absolute neutrophil count (ANC) > 1500 / mm3. (ANC >1000/mm3 may be considered in special circumstances such as benign cyclical neutropenia as judged by the investigator and in discussion with the sponsor). c. Platelet count >75,000 / mm3. d. Estimated creatinine clearance > 45ml / min. Refer to Appendix 10.3. e. Total bilirubin f. Aspartate amino transferase (AST) or alanine amino transferase (ALT) 8. Recovered from any previous therapy related toxicity to 9. Ability to take oral medication in the opinion of the investigator. 10. Age >= 18 years. 11. Written informed consent that is consistent with ICH-GCP guidelines.
Exclusion criteria
Exclusion criteria: 1. Prior treatment with EGFR directed small molecules or antibodies. 2. Curative intent chemoradiotherapy as the only treatment for stage IIIB NSCLC unless relapse occurs within 6 months of completion of treatment, and in the opinion of the investigator the patient has received an equivalent of 4 cycles of platinum-based doublet therapy. 3. Radiotherapy within 4 weeks prior to randomization, except as follows: a. Palliative radiation to target organs other than chest may be allowed up to 2 weeks prior to randomization, and b. Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling. 4. Active brain metastases (stable for 4 weeks, symptomatic, or leptomeningeal disease). Dexamethasone therapy will be allowed if administered as a stable dose for at least 4 weeks before randomization. 5. Any other current malignancy or malignancy diagnosed within the past three (3) years (other than basal-cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer). 6. Known pre-existing interstitial lung disease. 7. Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohns disease, malabsorption or CTC grade >=2 diarrhoea of any aetiology, based on investigator assessment. 8. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3 (Refer to Appendix 10.4), unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to randomisation. 9. Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug. 10. Women of child-bearing potential and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry, for the duration of study participation and for at least 2 months after treatment has ended. Adequate methods of contraception and Women of Child-Bearing Potential are discussed in Section 4.2.2.3. 11. Female patients of childbearing potential (see Section 4.2.2.3) who are nursing or are pregnant. 12. Patients unable to comply with the protocol in the opinion of the investigator. 13. Active hepatitis B infection (defined as presence of Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier. 14. Known or suspected active drug or alcohol abuse in the opinion of the investigator. 15. Requirement for treatment with any of the prohibited concomitant medications listed in Section 4.2.3. 16. Any contraindications for therapy with afatinib or erlotinib. 17. Known hypersensitivity to erlotinib, afatinib or the exipients of any of the trial drugs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Compare efficacy of afatinib with erlotinib as second-line treatment for patients with squamous cell carcinoma of the lung, as measured by progression-free survival (PFS).Timepoint: Time taken for the randomized patient to progress into the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survivalTimepoint: First objective response to the time of progression or death. | — |
Countries
Argentina, Austria, Canada, Chile, China, Democratic People's Republic of Korea, Denmark, France, Germany, Greece, Hungary, India, Ireland, Italy, Mexico, Netherlands, Peru, Portugal, Singapore, Spain, Taiwan, Turkey, United Kingdom, United States of America
Contacts
Public ContactDr Partha Gokhale
Boehringer-Ingelheim India Pvt Ltd
Outcome results
None listed