Clinical trial NCT00755170: Metronomic Vinorelbine and Bevacizumab in Patients With Non Small Cell Lung Cancer
Official title: A Phase II Study of the Combination of Metronomic Vinorelbine and Bevacizumab as 2nd Line Treatment in Patients With Non Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: Vinorelbine
Bevacizumab
Chemotherapy
Lead sponsor: Hellenic Oncology Research Group
Sponsor class: OTHER
Collaborators: name: University Hospital of Crete
First posted: 2008-09-18
Enrollment: 48
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: This trial will evaluate the efficacy and safety of metronomic vinorelbine and bevacizumab combination in patients with pretreated, advanced non small cell lung cancer

Detailed description: Intravenous (IV) vinorelbine is a standard chemotherapy option for the treatment of metastatic NSCLC, either alone or in combination with other agents such as CDDP or Carboplatin with overall response rates (ORR) of 15-35% as 1st line treatment and less than 10% as salvage treatment. For the past few years vinorelbine is available for per os (po) administration with acceptable and reliable pharmacokinetic profiles and with a bioavailability of approximately 40% of the IV dose. In randomized phase II studies IV and po vinorelbine have shown comparable response and overall survival rates. The low dose metronomic chemotherapy that is administered in short intervals has been shown in vitro an in vivo to have antiangiogenic effects. Bevacizumab is a well known anti-angiogenic agent. Recently, a phase III study of 1st line treatment in patients with advanced or metastatic NSCLC showed that the addition of bevacizumab to a platinum-based regimen provided a survival benefit. This study will evaluate the combination of metronomic vinorelbine and bevavizumab as 2nd line treatment of NSCLC.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed, metastatic (stage IV) non small cell lung cancer
* One previous platinum based chemotherapy regimen with or without taxanes for metastatic NSCLC
* Measurable disease, defined as at least 1 bidimensionally measurable lesion ≥ 20 X 10 mm
* Age ≥ 18 years
* Performance status (WHO) 0-2
* Life expectancy of at least 12 weeks
* Adequate bone marrow (ANC ≥ 1,500/mm3, PLT ≥ 100,000/mm3, Hgb ≥ 11 g/dL), liver (Bilirubin ≤ 1.5 upper normal limit, SGOT/SGPT ≤ 2.5 upper normal limit in the absence of liver metastases or ≤ 5 upper normal limit in the presence of liver metastases), and renal function (Creatinine ≤ 1,5 upper normal limit)
* Patients must be able to understand the nature of this study
* Written informed consent

Exclusion Criteria:

* Second primary malignancy, except for non-melanoma skin cancer. Pregnant or lactating women
* Any serious, uncontrolled comorbidity on the investigator's judgment
* Uncontrolled infection
* Any sustained chronic toxicity \> grade 2 according to the NCI CTCAE (version 3.0)
* Brain metastases, except if radiated and asymptomatic
* Radiotherapy within the previous 4 weeks
* Previous radiotherapy to the only measurable lesion
* Proteinuria ≥ 500 mgr of protein daily
* Hemoptysis \> 10 cc per event
* Clinically significant hematemesis
* Centrally located lesion or in contact with major vessels
* Pulmonary lesion with cavitation
* Documented hemorrhagic diathesis or coagulation disorder
* Cardiovascular disease (class II-IV NYHA congestive heart failure, myocardial infarction within the previous 4 months, unstable angina, LVEF \< normal, ventricular arrhythmia, uncontrolled hypertension)
* Thrombotic event within the previous 6 months
* Concurrent use of aspirin \> 325 mgr daily, low molecular weight heparin in therapeutic dose, warfarin or acenocoumarol, non-steroid anti-inflammatory agents
* Concurrent treatment with other anti-cancer drug
* Major surgical procedure within the previous 4 weeks
* Serum Να+ \< 120mg/dL

Primary outcomes:
measure: Response rate
timeFrame: Objective responses confirmed by CT or MRI (on 3rd and 6th cycle)
Secondary outcomes:
measure: Toxicity profile
timeFrame: Toxicity assessment on each cycle
measure: Progression free survival
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Alexandroupolis
country: Greece
facility: University General Hospital of Alexandroupolis, Dep of Medical Oncology
city: Athens
country: Greece
facility: "IASO" General Hospital of Athens, 1st 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 of Athens
city: Athens
country: Greece
facility: Air Forces Military Hospital of Athens
city: Heraklion
country: Greece
facility: University Hospital of Crete, Dep of Medical Oncology
city: Larissa,
country: Greece
facility: State General Hospital of Larissa, Dep of Medical Oncology
city: Thessaloniki
country: Greece
facility: "Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology
city: Thessaloniki
country: Greece
facility: Interbalkan Hospital, division of Oncology, Pylaia, Thessaloniki
Study officials:
affiliation: University Hospital of Crete, Dep of Medical Oncology
name: Sofia Agelaki, MD
role: PRINCIPAL_INVESTIGATOR
References: