Patients with Advanced Non Squamous Cell Non Small Cell Lung Cancer (NSCLC), first-line. MedDRA version: 12.0 Level: LLT Classification code 10025054 Term: Lung cancer non-small cell stage IIIB MedDRA version: 12.0 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV MedDRA version: 12.0 Level: PT Classification code 10029515 Term: Non-small cell lung cancer recurrent MedDRA version: 12.0 Level: PT Classification code 10029521 Term: Non-small cell lung cancer sta
Conditions
Interventions
Trade Name: Avastin
Product Name: Bevacizumab
Product Code: Ro 487-6646
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Concentratio
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Patients with histologically or cytologically proven non-squamous NSCLC stage IIIB with pleural effusion or stage IV •= 18 years of age •Performance status ECOG 0-2 •Estimated life expectancy of at least 12 weeks •Subjects with at least one measurable (CT or MRI) lesion according to RECIST •Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: - Hemoglobin = 9.0 g/dL - Absolute neutrophil count (ANC) = 1,500 /mm3 - Platelet count = 100 000/µL - Total bilirubin = 2 x ULN - ALT, AST and alkaline phosphatase (AP) = 2,5 x ULN - PT-INR/PTT =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Patient has received prior chemotherapeutic regimens for advanced disease. Prior chemotherapy given as neoadjuvant or adjuvant therapy for early stage disease, completed at least 12 months prior to diagnosis of advanced stage disease, will not be considered as exclusion criterion. •Patient has received prior EGFR-targeted therapy •Squamous-cell carcinoma (SCC) histology, SCLC histology or mixed histology •Evidence of tumor invading or abutting major blood vessels •Patient has signs or symptoms of acute infection requiring systemic therapy (acute or within the last 14 days) •Uncontrolled diabetes mellitus with HbA1c > 7,5% or elevated blood glucose levels levels of > 200 mg/dL •History of uncontrolled heart disease (congestive heart failure > NYHA class 2; active Coronary Arterial Disease (CAD), (MI more than 6 months prior to study entry is allowed); cardiac arrythmias requiring anti-arrythmic therapy (except, when controlled by beta blockers or digoxin) and/or uncontrolled hypertension (> 150/100 mmHg) •Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of erlotinib and (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection, total parenteral nutrition with lipids) •History of HIV infection or previously sero-positive for the virus •History of Hepatitis B or/and C or previously sero-positive for the Hepatitis B or/and C virus •Patients with seizure disorder requiring CYP3A4-inducing anti-epileptics •History of organ allograft •Patients with evidence or history of bleeding diathesis •History of thrombotic disorders within the last 6 months prior to enrolment •Fine needle biopsy or open biopsy within 1 week prior inclusion •Clinically symptomatic leptomeningeal or brain metastases (patients with clinically stable brain metastases may be enrolled) •Impaired wound healing, non-healing wounds, ulcers, fractures or any condition that provokes uncontrolled bleeding •Preexisting neuropathia ? grade 2 •History of grade =2 hemoptysis (bright red blood of at least 2.5 ml) •Patients undergoing renal dialysis •Past or current history of cancer other than the entry diagnosis EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry. •Any person being in an institution on assignment of the respective authority •Urine protein qualitative value of > 30 in urinalysis or > +1 in proteinuria testing by dipstick •Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information •Concomitant or intented anticoagulation therapy •Planned surgical or dental invasive intervention (e.g. tooth extraction, planned surgeries) during the course of the study •Any serious medical condition with organ impairment •Hypersensitivity to bevacizumab or erlotinib or any of their ingredients •Major surgery or significant traumatic injury within the last 4 weeks before inclusion •Parallel participation in another clinical trial or participation in another clinical trial within the last 30 days or 7 half-life's, whatever is of longer duration, prior study start •Pregnancy, breast feeding •Claustrophobia •Known allergic reaction to Gadolinium •Heart pacemaker •Ferromagnetic and electronic implants in special locations (e. g. cerebral) •Coc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the accuracy of imaging findings in FDG-/FLT-PET and DCE-MRI after one week of treatment for early prediction of RECIST-based non-progression (CR+PR+SD) after 6 weeks of therapy in patients with NSCLC stage IIIb/IV treated first line with erlotinib and bevacizumab. To evaluate the accuracy of imaging findings in FDG-/FLT-PET and DCE-MRI after one week of treatment for early prediction of PFS in patients with NSCLC stage IIIb/IV treated first line with erlotinib and bevacizumab. ;Secondary Objective: To identify imaging characteristics after one week of treatment predicting RECIST-defined progressive disease (PD), stable disease (SD) and response after 6 weeks of treatment with erlotinib and bevacizumab. To compare the potential of FDG-/FLT-PET and DCE-MRI for early prediction of non-progression. To compare the potential of FDG-/FLT-PET and DCE-MRI regarding patient prognosis. To compare imaging characteristics after one and after 6 weeks of treatment with regard to their predictive potential for therapy outcome. To compare EGFR- and KRAS-mutational status and imaging characteristics with regard to their potential for early prediction of non-progression. To describe the correlation between pharmacokinetics of bevacizumab and erlotinib with imaging results and clinical outcome, To determine the efficacy of the combination therapy descriptively (reponse rate [RR], progression free survival [PFS], time on treatment [TOT], disease control rates [DCR], overall survival [OS]).;Primary end point(s): ROC analysis of baseline values and changes in SUVs of FDG-/FLT-PET. ROC analysis of baseline values and changes in Ktrans/kep/Ki/IAUC for DCE-MRI. Explorative analysis of BF, BV, PS and MTT values and changes during treatment in DCE-MRI. PFS/OS analysis with possibly predefined cut-off values in FDG-/FLT-PET for metabolic response. Correlation of baseline values and analysis of possibly predefined cut-off values in correlation with PFS/OS/RR. Statis | — |
Countries
Germany
Outcome results
None listed