An Open-label Randomized Phase II Trial of Gemcitabine and Cisplatin With or Without Bevacizumab in EGFR Wild-type Non-squamous Non-small-cell Lung Cancer Patients
Overview
- Phase
- Phase 2
- Intervention
- cisplatin and gemcitabine combination with Bevacizumab
- Conditions
- Lung Cancer
- Sponsor
- Sichuan Cancer Hospital and Research Institute
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- disease-free time to progression
- Last Updated
- 13 years ago
Overview
Brief Summary
Advanced non-small-cell lung cancer (NSCLC) patients without epidermal growth factor receptor (EGFR) mutations show a poor prognosis. Gemcitabine combined with cisplatin chemotherapy is an effective treatment measures for EGFR mutation-negative NSCLC patients, but the prognosis remains poor. Chemotherapy combined with targeted monoclonal antibody treatment may be better treatment options in these patients. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Bevacizumab blocks the ability of tumors to grow new blood vessels and spread. It is not yet known whether cisplatin and gemcitabine is more effective when given alone or with bevacizumab. This randomized trial studies how well giving cisplatin and gemcitabine alone or in combination with Bevacizumab (Avastin) works in treating patients with stage IIIB/IV non-squamous NSCLC without EGFR mutations.
Detailed Description
Lung cancer is the leading cause of cancer morbidity and mortality worldwide. The majority of lung cancer is nonsquamous NSCLC. EGFR tyrosine kinase inhibitors (EGFR-TKI) is a effective first-line treatment for EGFR mutations non-squamous NSCLC treatment. But those patients without epidermal growth factor receptor (EGFR) mutations show a poorer prognosis. Gemcitabine combined with cisplatin chemotherapy is an effective treatment measures for EGFR mutation-negative NSCLC patients, but the prognosis remains poor. Chemotherapy combined with targeted monoclonal antibody treatment may be better treatment options in these patients. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Bevacizumab blocks the ability of tumors to grow new blood vessels and spread. This randomized trial studies how well giving cisplatin and gemcitabine alone or in combination with Bevacizumab (Avastin) works in treating patients with stage IIIB/IV non-squamous NSCLC without EGFR mutations. Accordingly, we have come to a scientific hypothesis that cisplatin and gemcitabine combination with Bevacizumab might be a better treatment strategy for stage IIIB/IV non-squamous NSCLC patients with EGFR wild-type. It can improve the PFS of stage IIIB/IV non-squamous NSCLC patients with EGFR wild-type. The primary endpoint is disease-free time to progression (PFS). The secondary study endpoint is objective response rate (ORR), disease control rate (DCR), safety and quality of life (QOL). Through this study lay the foundation for further exploration of the non-squamous NSCLC first-line treatment in patients with EGFR wild-type strategy, and guide the rational application of bevacizumab.
Investigators
Juan Li, MD
attending physician
Sichuan Cancer Hospital and Research Institute
Eligibility Criteria
Inclusion Criteria
- •Histologic documentation of primary lung carcinoma, non-squamous histology with EGFR mutation Negative.
- •Stage IIIB/IV disease according to the 7th Edition of the American Joint Committee on Cancer staging system
- •Not received radiotherapy, chemotherapy or other biological treatment
- •Measureable disease
- •Life expectancy of \>= 12 months
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
- •Absolute neutrophil count (ANC) \>= 2, 500/mm\^3
- •Platelet count \>= 100,000/mm\^3
- •Hemoglobin \>= 9.0 g/dL
- •Total bilirubin =\< 1.5 x upper limit of normal (ULN)
Exclusion Criteria
- •Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component
- •Prior chemotherapy or treatment for metastatic non-small cell lung cancer
- •Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive, per MD discretion
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- •Other active malignancy =\< 3 years prior to randomization; EXCEPTIONS: Non melanotic skin cancer or carcinoma-in-situ of the cervix
- •History of myocardial infarction or other evidence of arterial thrombotic disease (angina)
- •History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) =\< 6 months prior to randomization
- •Ongoing or active infection, symptomatic congestive heart failure , cardiac arrhythmia, psychiatric illness/social situations, or any other medical condition that would limit compliance with study requirements
- •History of bleeding diathesis or coagulopathy
Arms & Interventions
Arm I: bevacizumab plus chemotherapy
Patients in the experimental arm receive cisplatin and gemcitabine combination with Bevacizumab. GP chemotherapy (gemcitabine 1250mg/m2 IV D1 and D8 plus cisplatin 75mg/m2 IV D1, every 21-day cycle) plus bevacizumab (7.5 mg/kg IV on D1 of every 21-day cycle).
Intervention: cisplatin and gemcitabine combination with Bevacizumab
Arm II: chemotherapy
Patients receive gemcitabine combined with cisplatin chemotherapy((gemcitabine 1250mg/m2 IV D1 and D8 plus cisplatin 75mg/m2 IV D1, every 21-day cycle) ) every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Gemcitabine combined with cisplatin chemotherapy
Outcomes
Primary Outcomes
disease-free time to progression
Time Frame: 6 week
Secondary Outcomes
- quality of life(6 week)