Multicenter Evaluation of Docetaxel, Gemcitabine, and Bevacizumab Combination Followed by Bevacizumab Alone in Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Phase 2

Terminated

Conditions: Non-small Cell Lung Cancer

Interventions: Drug: docetaxel
Drug: gemcitabine
Drug: bevacizumab

Registration Number: NCT00378573

Lead Sponsor: Sanofi

Brief Summary: This is a Phase II prospective, multicenter study evaluating Progression Free Survival (PFS) after first line treatment with the combination of gemcitabine, docetaxel, and bevacizumab in subjects with advanced or metastatic Non-Small Cell Lung Cancer (NSCLC). PFS will be measured from the date of registration (ie, assignment of subject number when subject meets all entry criteria) to the earliest date of documented evidence of progressive disease, or the date of death due to any cause, whichever occurs first.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 17

Inclusion Criteria

Histologic or cytologic confirmation of locally advanced (pleural effusion) or metastatic (Stage IIIB/IV) NSCLC (non-squamous-cell histology only), mixed tumor types can be selected based on predominant cell type unless small cell elements are discovered (in which case the subject is not eligible);
Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >/= 20 mm with conventional computerized tomography (CT) or magnetic resonance imaging (MRI) scans, or as >/= 10 mm with spiral computerized tomography (CT) scan
No previous systemic chemotherapy
Estimated life expectancy of >/= 12 weeks
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2
Nonpregnant, nonlactating female subjects; male and female subjects of childbearing potential must be willing to use an effective form of contraception while on therapy and for 90 days thereafter; an effective form of contraception is defined as an oral contraceptive or a double barrier method; pregnancy is to be determined/ ruled out through the use of serum human chorionic gonadotropin (HCG)
Subjects must have adequate renal function as determined by the following within 1 week prior to study registration: Calculated creatinine clearance >45 mL/min using Cockcroft-Gault formula; Urine protein: creatinine (UPC) ratio <1.0 by spot urinalysis; Urine dipstick for protein <2+ (subjects 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 to be eligible);
Hematologic evaluation within 2 weeks prior to study registration (minimum values): Absolute neutrophil count (ANC) >/= 1500 mm3; Platelet count >/= 100,000 mm3; Hemoglobin (Hg) >/= 9.9 g/dL (erythropoietin may be transfused to maintain or exceed this level); Partial thromboplastin time (PTT) no greater than upper limit of normal (ULN)
Hepatic function evaluation within 2 weeks prior to study registration (as detailed in protocol provided to Investigator): Total bilirubin </= upper limit of normal; Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase must be within the range allowing for eligibility; In determining eligibility the more abnormal of the two values (AST or ALT) should be used (details for decision in full protocol as provided to Investigator)

Exclusion Criteria

Receipt of prior systemic chemotherapy, vascular endothelial growth factor (VEGF) or endothelial growth factor receptor (EGFR) inhibitor therapy at any time; receipt of recent or current radiation therapy; current, recent (within 4 weeks prior to study registration), or planned receipt of investigational therapy (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication)
Subjects with cardiovascular diseases and related treatments
Surgical procedure in anamnesis (medical history): Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, or anticipation of need for major surgical procedure during the course of the study; Minor surgical procedures (eg, fine needle aspirations, core biopsies) within 7 days prior to registration;
Serious non-healing wound, ulcer, or bone fracture;
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study registration;
History of gross hemoptysis (defined as bright red blood of >/= 0.5 teaspoon)
History of hypersensitivity reaction to drugs formulated with polysorbate 80;
Subjects with brain metastases;
Peripheral neuropathy >/= Grade 2 (based on Common Toxicity Criteria Adverse Event [CTCAE] v3.0);
History of a malignancy other than NSCLC; exceptions to this include: Curatively treated basal cell carcinoma; cervical intraepithelial neoplasia; or localized prostate cancer with a current prostate-specific antigen (PSA) of <1.0 ng/dL on 2 successive evaluations at least 3 months apart, and the most recent evaluation within 4 weeks of study registration; History of another malignancy that was curatively treated and no evidence of disease for a minimum of 5 years;
Symptoms of a clinically meaningful illness in the 90 days before the study, or history of other disease, (such as human immunodeficiency virus (HIV) positive, chronic infection (eg, pulmonary tuberculosis), or hepatitis A, B or C (active or previously treated), active infection with fever, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that might affect the interpretation of the results of the study, or render the subject at high risk from treatment complications; (testing for these conditions will be at investigator discretion)
Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
docetaxel, gemcitabine and bevacizumab	bevacizumab	Single arm treatment with docetaxel, gemcitabine and bevacizumab
docetaxel, gemcitabine and bevacizumab	docetaxel	Single arm treatment with docetaxel, gemcitabine and bevacizumab
docetaxel, gemcitabine and bevacizumab	gemcitabine	Single arm treatment with docetaxel, gemcitabine and bevacizumab

Primary Outcome Measures

Name	Time	Method
Progression Free Survival for Subjects With Locally Advanced or Metastatic (Stage IIIB or Stage IV) Non-Small Cell Lung Cancer (NSCLC) After Systemic Treatment With Gemcitabine, Docetaxel, and Bevacizumab as First Line Therapy	1 year post-registration

Secondary Outcome Measures

Name	Time	Method
Overall Survival	2 years post-registration	Survival is defined as the time from the date of registration to the study to the date of death.
Objective Response Rate (Complete Response [CR] Plus Partial Response [PR]) Using Response Evaluation Criteria in Solid Tumors (RECIST)	1 year from start of treatment	Complete response is defined as disappearance of all target and nontarget lesions identified and reported at baseline (at or within 4 weeks before the beginning of treatment) by image-based evaluations such as computerized tomography (CT) or magnetic resonance imaging (MRI). Partial response is defined as persistence of one or more nontarget lesions and at least 30 percent decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters.