Cisplatin/Vinorelbine/Bevacizumab Followed by Docetaxel/Gemcitabine/Bevacizumab Versus the Cisplatin/Docetaxel/Bevacizumab Combination in Locally Advanced or Metastatic NSCLC

NCT ID: NCT00620971

Last Updated: 2014-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2010-04-30

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.

Conditions

Non Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

NC/Avastin-\>DG/Avastin

Group Type: EXPERIMENTAL

Vinorelbine

Intervention Type: DRUG

Vinorelbine (oral) 60 mg/m2, on days 1 and 8 every 3 weeks for 3 cycles

Cisplatin

Intervention Type: DRUG

Cisplatin (IV) 80 mg/m2 on day 1 every 3 weeks for 3 cycles

Bevacizumab

Intervention Type: DRUG

Bevacizumab (IV) 15 mgr/Kgr on day 1 every 3 weeks for 3 cycles

Docetaxel

Intervention Type: DRUG

Docetaxel (IV) 75 mg/m2 on day 1 every 3 weeks for 6 cycles

Gemcitabine

Intervention Type: DRUG

Gemcitabine(IV) 1,100 mg/m2 on day 1 and d8 every 3 weeks for 6 cycles

Bevacizumab

Intervention Type: DRUG

Bevacizumab (IV) 15 mgr/Kgr on day 1 every 3 weeks for 6 cycles

2

DG/Avastin

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Docetaxel (IV) 75 mg/m2 on day 1 every 3 weeks for 6 cycles

Cisplatin

Intervention Type: DRUG

Cisplatin (IV) 80 mg/m2 on day 1 every 3 weeks for 6 cycles

Bevacizumab

Intervention Type: DRUG

Bevacizumab (IV) 15 mgr/Kgr on day 1 every 3 weeks for 6 cycles

Interventions

Vinorelbine

Vinorelbine (oral) 60 mg/m2, on days 1 and 8 every 3 weeks for 3 cycles

Intervention Type: DRUG

Cisplatin

Cisplatin (IV) 80 mg/m2 on day 1 every 3 weeks for 3 cycles

Intervention Type: DRUG

Bevacizumab

Bevacizumab (IV) 15 mgr/Kgr on day 1 every 3 weeks for 3 cycles

Intervention Type: DRUG

Docetaxel

Docetaxel (IV) 75 mg/m2 on day 1 every 3 weeks for 6 cycles

Intervention Type: DRUG

Gemcitabine

Gemcitabine(IV) 1,100 mg/m2 on day 1 and d8 every 3 weeks for 6 cycles

Intervention Type: DRUG

Bevacizumab

Bevacizumab (IV) 15 mgr/Kgr on day 1 every 3 weeks for 6 cycles

Intervention Type: DRUG

Docetaxel

Docetaxel (IV) 75 mg/m2 on day 1 every 3 weeks for 6 cycles

Intervention Type: DRUG

Cisplatin

Cisplatin (IV) 80 mg/m2 on day 1 every 3 weeks for 6 cycles

Intervention Type: DRUG

Bevacizumab

Bevacizumab (IV) 15 mgr/Kgr on day 1 every 3 weeks for 6 cycles

Intervention Type: DRUG

Other Intervention Names

Navelbine; CDDP; Avastin; Taxotere; Gemzar; Avastin; Taxotere; CDDP; Avastin

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital of Crete

OTHER

Sponsor Role: collaborator

Hellenic Oncology Research Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vassilis Georgoulias, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Crete, Dep of Medical Oncology

Locations

University General Hospital of Alexandroupolis, Dep of Medical Oncology

Alexandroupoli, , Greece

"Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine

Athens, , Greece

"Metaxa's" Anticancer Hospital of Piraeus,1st Dep of Medical Oncology

Athens, , Greece

401 Military Hospital, Medical Oncology Unit

Athens, , Greece

Air Forces Military Hospital, Dep of Medical Oncology

Athens, , Greece

IASO" General Hospital of Athens, 1st Dep of Medical Oncology

Athens, , Greece

Sismanogleio General Hospital, 1st, 2nd Dep of Pulmonary Diseases

Athens, , Greece

Sotiria" General Hospital, 1st, 3rd, 8th Dep of Pulmonary Diseases

Athens, , Greece

"Theagenion" Anticancer Hospital of Thessaloniki

Thessaloniki, , Greece

Countries

Greece

References

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.

Reference Type: DERIVED

PMID: 25662596 (View on PubMed)

Other Identifiers

CT/07.19

Identifier Type: -

Identifier Source: org_study_id