Clinical trial NCT00620971: Cisplatin/Vinorelbine/Bevacizumab Followed by Docetaxel/Gemcitabine/Bevacizumab Versus the Cisplatin/Docetaxel/Bevacizumab Combination in Locally Advanced or Metastatic NSCLC
Official title: Sequential Cisplatin/Vinorelbine/Bevacizumab Followed by Docetaxel/Gemcitabine/Bevacizumab Versus Cisplatin/Docetaxel/Bevacizumab in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: Non Small Cell Lung Cancer
Cisplatin
VInorelbine
Docetaxel
Gemcitabine
Bevacizumab
Lead sponsor: Hellenic Oncology Research Group
Sponsor class: OTHER
Collaborators: name: University Hospital of Crete
First posted: 2008-02-22
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial will evaluate whether the sequential administration of Cisplatin/Vinorelbine/Bevacizumab followed by Docetaxel/Gemcitabine/Bevacizumab versus the Cisplatin/Docetaxel/Bevacizumab combination as first line treatment offers a survival advantage in patients with locally advanced or metastatic NSCLC.

Detailed description: An unanswered question in first line treatment of non small cell lung cancer (NSCLC) is whether the administration of more than 2 active drugs provides greater efficacy than a two-drug combination. Docetaxel/gemcitabine combination is a well tolerated regimen, which has comparable efficacy to docetaxel/cisplatin or vinorelbine/cisplatin. In a recent phase II study in first line treatment of advanced or metastatic NSCLC, the sequential administration of vinorelbine/cisplatin followed by docetaxel/gemcitabine produced a response rate of 45.8% and a 1-year survival rate of 51%. The addition of bevacizumab to a platinum-based regimen provided a survival benefit in patients with advanced or metastatic NSCLC.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed, unresectable locally advanced (stage IIIB with pleural effusion) or metastatic (stage IV) non-squamous NSCLC
* Performance status (WHO) 0-1
* Adequate bone marrow (ANC ≥ 1,500/mm3, PLT ≥ 100,000/mm3, Hgb ≥ 11 g/dL), liver (Bilirubin ≤ 1.5 UNL, SGOT/SGPT ≤ 2.5 UNL, ALP ≤ 5 UNL), and renal function (Creatinine ≤ UNL - if borderline, creatinine clearance should be ≥ 60 mL/min)
* No previous chemotherapy or immunotherapy for advanced/metastatic NSCLC is allowed

  --Previous radiotherapy is allowed provided that the measurable lesions are outside the radiation fields
* Measurable disease, defined as at least 1 bidimensionally measurable lesion ≥ 20 X 10 mm
* Patient able to take oral medication
* Absence of active CNS disease
* Paraffin embedded sample of primary or metastatic tumor diagnostic specimen must be available
* Patients must be able to understand the nature of this study and give written informed consent

Exclusion Criteria:

* Pregnant or lactating women
* Women of child-bearing age unable or unwilling to take effective contraceptive measures
* Active CNS disease, brain metastases, or leptomeningeal involvement
* Symptomatic neuropathy \> grade1 according to the NCI CTCAE (version 3.0)
* Cardiovascular disease (class II-IV NYHA congestive heart failure, myocardial infarction within the previous 4 months, LVEF \< normal, uncontrolled hypertension, ventricular arrhythmia), anticoagulation treatment or thrombotic event within the previous 6 months
* Active infection, requiring IV antibiotic treatment, within the previous 2 weeks
* Long-term oxygen therapy
* Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer
* Radiotherapy within the previous 4 weeks
* Previous radiotherapy to the only measurable lesion
* Concurrent treatment with other anti-cancer drug
* Uncontrolled hypercalcemia
* Known allergy to drugs with similar chemical structure to study drugs. Concurrent corticosteroids, except for chronic therapy with methylprednisolone ≤ 20 mgr daily (or equivalent) for more than one month

Primary outcomes:
measure: Overall Response Rate
timeFrame: Objective responses confirmed by CT or MRI (on 3rd and 6th cycle)
Secondary outcomes:
measure: Time to Tumor Progression
timeFrame: 1-year
measure: Overall Survival
timeFrame: 1 year
measure: Quality of life assessment
timeFrame: Assessment every two cycles
Other outcomes:
Locations:
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: "Metaxa's" Anticancer Hospital of Piraeus,1st Dep of Medical Oncology
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: Thessaloniki
country: Greece
facility: "Theagenion" Anticancer Hospital of Thessaloniki
Study officials:
affiliation: University Hospital of Crete, Dep of Medical Oncology
name: Vassilis Georgoulias, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kotsakis A, Kentepozidis N, Emmanouilidis Ch, Polyzos A, Agelidou A, Vaslamatzis M, Chandrinos V, Agelaki S, Vamvakas L, Kalbakis K, Katsaounis P, Stoltidis D, Nintos G, Hatzidaki D, Vetsika EK, Mavroudis D, Georgoulias V. Sequential administration of vinorelbine plus cisplatin and bevacizumab followed by docetaxel plus gemcitabine and bevacizumab compared to docetaxel plus cisplatin and bevacizumab regimen as first-line therapy for advanced or metastatic non-squamous non-small cell lung cancer: A multicenter randomized phase II trial of the Hellenic Oncology Research Group (HORG). Lung Cancer. 2015 Apr;88(1):57-62. doi: 10.1016/j.lungcan.2015.01.012. Epub 2015 Jan 23.