Clinical trial NCT00749567: Combination of Erlotinib and Bevacizumab as Second-line Treatment in Patients With Non-small Cell Lung Cancer
Official title: Combination of Erlotinib (Tarceva®) and Bevacizumab (Avastin®) as Second-line Treatment in Locally Advanced / Metastatic, Non-squamous, Non-small Cell Lung Cancer (NSCLC) Patients: A Phase II Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-small-cell Lung Cancer
Keywords: NSCLC
TKI's
Anti-VEGF
Lead sponsor: Hellenic Oncology Research Group
Sponsor class: OTHER
Collaborators: name: University Hospital of Crete
First posted: 2008-09-09
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and toxicity of combination of erlotinib and bevacizumab in patients with locally advanced or metastatic, non-squamous non-small cell lung cancer, who progressed after first line treatment. Pretreatment with one of the two agents would not excluded patients from the study, in order to evaluate whether the combination of the two biologic agents could reverse tumor resistance.

Detailed description: A randomized, placebo-controlled phase III trial of erlotinib versus placebo, demonstrated that therapy with this tyrosine kinase inhibitor (TKI) prolongs survival after first or second line therapy in patients with advanced NSCLC. Moreover, the addition of bevacizumab, a monoclonal antibody against Vascular Endothelial Growth Factor bevacizumab (VEGF), to systemic chemotherapy, improved both the response rates and the time to tumor progression in two trials. Early data from phase I/II trials examining the combination of these two biological agents in pre-treated patients with non-squamous NSCLC, showed no major pharmacokinetic interactions and promising clinical activity.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed, unresectable locally advanced (stage IIIB with pleural effusion) and/or metastatic (stage IV) NSCLC
* Progression to first-line therapy for advanced/metastatic NSCLC
* Bi-dimensionally measurable disease (not included in radiation field)
* ECOG performance status of 0-2
* Life expectancy of more than 6 months
* Adequate liver (serum bilirubin \<1.5 times the upper normal limit, AST and ALT \<2.5 times the upper normal limit in the absence of demonstrable liver metastases, or \<5 times the upper normal limit in the presence of liver metastases,adequate renal function (serum creatinine \<1.5 times the upper normal limit),and bone marrow (neutrophils ≥ 1.5x 109 /L, and platelets ≥ 100x 109 /L) function
* Signed informed consent

Exclusion Criteria:

* Central nervous system involvement (unless if the patient has being previously irradiated and is clinically stable)
* Presence of a centrally located mass or a tumor mass in close relation to large vessels or a mass with cavitation.
* Surgery or radiation therapy within the last 14 days from study entry
* Active infection
* History of life-threatening hemoptysis / hematemesis, history of thrombosis or use of anti-coagulation therapy
* History of significant cardiac disease (unstable angina, congestive heart failure, myocardial infarction, ventricular arrhythmias) or stroke within the previous 6 months or uncontrolled hypertension
* Patients on other experimental treatment protocols
* History of a second primary malignancy (other than basal-cell skin carcinoma or in situ carcinoma of the cervix)
* Psychiatric illness or social situation that would preclude study compliance
* Pregnant or lactating women

Primary outcomes:
measure: Overall response rate
timeFrame: Objective responses confirmed by CT or MRI (on 3rd and
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 1 year
measure: Overall Survival
timeFrame: 1 year
measure: Quality of life assessment
timeFrame: Assessment every two cycles
measure: Toxicity profile
timeFrame: Assessment every two cycles
Other outcomes:
Locations:
city: Heraklion
country: Greece
facility: University Hospital of Heraklion
state: Crete
city: Alexandroupolis
country: Greece
facility: University General Hospital of Alexandroupolis, Dep of Medical Oncology
city: Athens
country: Greece
facility: "Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine
city: Athens
country: Greece
facility: 401 Military Hospital, Medical Oncology Unit
city: Athens
country: Greece
facility: Air Forces Military Hospital, Dep of Medical Oncology
city: Athens
country: Greece
facility: IASO" General Hospital of Athens, 1st Dep of Medical Oncology
city: Athens
country: Greece
facility: Sismanogleio General Hospital, 1st, 2nd Dep of Pulmonary Diseases
city: Athens
country: Greece
facility: Sotiria" General Hospital, 1st, 3rd, 8th Dep of Pulmonary Diseases
city: Piraeus
country: Greece
facility: "Metaxa's" Anticancer Hospital of Piraeus,1st Dep of Medical Oncology
city: Thessaloniki
country: Greece
facility: Theagenion" Anticancer Hospital of Thessaloniki
Study officials:
affiliation: University Hospital of Crete, Dep of Medical Oncology
name: Sofia Agelaki, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Crete
name: Manolis Kontopodis, MD
role: PRINCIPAL_INVESTIGATOR
References: