Trial with erlotinib and bevacizumab in patients with advanced non-small cell lung cancer harboring specific gene changes in the epithelial growth factor receptor
- Conditions
- Advanced NSCLC harbouring EGFR mutations (del19 or L858R).MedDRA version: 15.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-004481-15-FR
- Lead Sponsor
- ETOP (European Thoracic Oncology Platform)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 102
- 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 < 1.5 × ULN, ALT and/or AST < 2.5 ×ULN, alkaline phosphatase < 5 ULN, except in the presence of exclusive bone metastases and in the absence of any liver disorder.
- Adequate renal function: Calculated creatinine clearance ? 50 mL/min (Cockroft-Gault) and proteinuria < 2+ (dipstick).
- Oral swallowing capability, patient capable of proper therapeutic compliance, and accessible for correct follow-up.
- Life expectancy of at least 2 months.
- Women of childbearing age, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before beginning treatment.
- All sexually active men and women of childbearing age must use an effective contraceptive method during the study treatment and for a period of at least 12 months following the last administration of trial drugs.
- Written Informed Consent (IC) must be signed and dated by the patient and the investigator prior to any trial-related intervention for
a) trial treatment
b) tissue submission for central review and central EGFR testing
Disease characteristics
- Pathological diagnosis of predominantly non-squamous, non-small-cell lung cancer (NSCLC).
- TNM version 7 stage IV disease including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease not amenable to curative treatment (including patients progressing after radio-chemotherapy for stage III disease).
- Measurable or evaluable disease (according to RECIST 1.1 criteria).
- Centrally confirmed EGFR exon 19 deletion (del19) or exon 21 mutation (L858R).
- Patients with asymptomatic and stable cerebral metastases
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 68
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 34
- Patients with increased risk of bleeding, defined by:
- major surgery or significant traumatic injury within 28 days prior to inclusion
- minor surgery (including permanent catheter insertion) within 24 hours prior to first treatment with bevacizumab
- 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
- uncontrolled hypertension (systolic blood pressure > 150 mm Hg and / or diastolic > 100 mm Hg)
- Patients with clinically significant cardiovascular diseases, including
- cerebral vascular accident (<6 months before inclusion)
- acute myocardial infarction (<6 months before inclusion)
- unstable angina
- congestive heart failure class > 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/inhib
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method