Cisplatin and Gemcitabine With or Without Bevacizumab in EGFR Wild-type Non-Small Cell Lung Cancer

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

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.

Study Overview

• Status: Unknown
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: cisplatin and gemcitabine combination with Bevacizumab; Drug: Gemcitabine combined with cisplatin chemotherapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • Sichuan Cancer Hospital
      • Contact: yu dong, MD; Phone Number: + 8618908178728; Email: dongyu5610@163.com
    • Chengdu, Sichuan, China, 610041
      • Not yet recruiting
      • Sichuan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x ULN in patients without liver or bone metastases; < 5 x ULN in patients with liver or bone metastases
• Cockcroft-Gault calculated creatinine clearance of >= 45 ml/min or creatinine =< 1.5 x ULN
• Prothrombin time (PT) =< 1.5 x ULN
• Partial thromboplastin time (PTT) =< ULN
• Urine dipstick proteinuria < 2+ * Note: Patients discovered to have >= 2 + proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate < 1 g of protein in 24 hours
• Negative pregnancy test done =< 7 days prior to randomization, for women of childbearing potential only
• Provide informed written consent
• Willing to return to Sichuan cancer hospital for follow-up
• Willing to provide tissue and blood samples for correlative research purposes

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
• Inadequately controlled hypertension (systolic blood pressure of > 150 mmHg or diastolic pressure > 100 mmHg on anti-hypertensive medications)
• Serious non-healing wound, ulcer, bone fracture, or have undergone a major surgical procedure, open biopsy, or significant traumatic injury =< 28 days or core biopsy =< 7 days prior to randomization
• History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess =< 6 months prior to randomization
• History of hemoptysis >= grade 2 (defined as bright red blood of at least 2.5 mL) =< 3 months prior to randomization
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: cisplatin and gemcitabine combination with Bevacizumab; Patients receive gemcitabine and cisplatin chemotherapy combined with Bevacizumab every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Gemcitabine 1250mg/m2 d1, d8, cisplatin 75mg/m2 d1, Bevacizumab 7.5 mg / kg every 21 days.; Other Names: AVASTIN
Active Comparator: 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.	Drug: Gemcitabine combined with cisplatin chemotherapy; Patients receive gemcitabine combined with cisplatin chemotherapy every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Gemcitabine 1250mg/m2 d1, d8, + cisplatin 75mg/m2 d1.; Other Names: Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
disease-free time to progression	6 week

Secondary Outcome Measures

Outcome Measure	Time Frame
quality of life	6 week

Collaborators and Investigators

• Sponsor: Sichuan Cancer Hospital and Research Institute

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Anticipated): August 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: June 15, 2012
• First Submitted That Met QC Criteria: June 15, 2012
• First Posted (Estimate): June 19, 2012

Study Record Updates

• Last Update Posted (Estimate): February 12, 2013
• Last Update Submitted That Met QC Criteria: February 11, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: cisplatin; Bevacizumab; gemcitabine; EGFR wild-type
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Gemcitabine; Cisplatin; Bevacizumab
• Other Study ID Numbers: WJP001