Advanced NSCLC harbouring EGFR mutations (del19 or L858R). MedDRA version: 17.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
ETOP (European Thoracic Oncology Platform)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age = 18 years - ECOG performance status 0-2 - Adequate haematological function: haemoglobin > 9 g/dL, neutrophils count >1.5×109/L, platelet count > 100 × 109/L - Adequate coagulation: INR = 1.5 - Adequate liver function: Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 34
Exclusion criteria
Exclusion criteria: - Patients with increased risk of bleeding, defined by: - major surgery or significant traumatic injury within 28 days prior to inclusion - minor surgery within 7 days prior, or placement of a vascular device within 2 days prior to enrolment - history or evidence of bleeding diathesis or hereditary coagulopathy - history of haemoptysis (defined as at least half a teaspoon’s emission of red blood) in the 3 months prior to inclusion) - evidence by CT of tumor cavitations, or tumours invading or abutting major blood vessels - inadequately controlled hypertension (systolic blood pressure > 150 mm Hg and / or diastolic > 100 mm Hg) - prior history of hypertensive crisis or hypertensive encephalopathy - Patients with clinically significant cardiovascular diseases, including - cerebral vascular accident ( NYHA II - serious cardiac arrhythmia requiring medication during the study and which could interfere with regularity of study treatment or is not controlled with medication. - Patients with a history of thrombosis or thromboembolism in the 6 months prior to treatment - Patients with gastrointestinal problems including - intestinal transit problems (such as malabsorption syndrome, chronic intestinal inflammatory disease, or other pathologies that can alter absorption of the medication - history of abdominal fistula, intestinal perforation or intra-abdominal abscess within 6 months prior to inclusion - uncontrolled active peptic ulcer - presence of trachea-oesophageal fistula. - Patients with neurologic problems, including - evidence of spinal cord compression - significant neurological or psychiatric disorders (including dementia and epileptic seizures). - Patients who have had in the past 5 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ breast carcinoma. - Patients with any known significant ophthalmologic anomaly of the ocular surface. - Patients with other serious diseases or clinical conditions, including but not limited to uncontrolled active infection and any other serious underlying medical processes that could affect the patient’s capacity to participate in the study. - Known hypersensitivity to bevacizumab or erlotinib or any of its excipients. - Patients who received prior chemotherapy for metastatic disease. - Patients who received previous treatment for lung cancer with drugs targeting EGFR or VEGF. - Patients who received treatment with an investigational drug agent during the 3 weeks before enrolment in the study. - Patients with current or recent use (within the last 10 days) of full doses of anticoagulants or thrombolytics, either orally or parenterally. Use of anticoagulant prophylaxis is permitted (low dose heparin or aspirin <=325 mg, prophylactic FXa inhibitors). - Patients with concurrent use of CYP3A4 inducers/inhibitors (such as, but not limited to, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, or grapefruit or grapefruit juice).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine progression free survival (PFS) of patients with advanced non-squamous NSCLC harbouring at diagnosis EGFR mutations with and without T790M mutation, treated with the combination of erlotinib and bevacizumab. Hypotheses of interest: When treated with bevacizumab and erlotinib a. Median PFS increases to 18 months for patients with EGFR T790M mutation b. Median PFS is approximately 18 months or more in patients without EGFR T790M mutation.;Secondary Objective: - To evaluate secondary measures of clinical efficacy including overall survival (OS), time to treatment failure (TTF), objective response rate (ORR), disease control rate (DCR) and duration of response (DR). - To assess the safety and the tolerability of the erlotinib and bevacizumab combination. - To evaluate the correlation of BRCA1 mRNA and AEG-1 mRNA expression and T790M with progression-free survival. - To monitor EGFR mutations (including T790M) in serum and plasma longitudinally. - To evaluate molecular biomarkers related to EGFR TKI and bevacizumab. - To determine the feasibility of re-biopsies at the time of progression and geneexpression arrays for decision-making for second-line treatment - To study the feasibility of recommending customized second-line chemotherapy based on BRCA1 and AEG-1 mRNA levels.;Primary end point(s): - Progression-free survival (PFS is defined as the time from the date of enrolment until documented progression or death, whichever occurs first);Timepoint(s) of evaluation of this end point: The final evaluation will be done within 6 months after the last visit of the last patient, approximately 54 months after the inclusion of the first patient. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival (OS) - Time to treatment failure (TTF) - Objective response (OR) - Adverse events graded according to CTCAE V4.0 - Disease control (DC) - Duration of response (DR);Timepoint(s) of evaluation of this end point: The final evaluation will be done within 6 months after the last visit of the last patient, approximately 54 months after the inclusion of the first patient. | — |
Countries
Denmark, France, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Switzerland, United Kingdom
Contacts
Public ContactETOP Coordinating Office
ETOP
Outcome results
None listed