Non-small Cell Lung Cancer
Conditions
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.
Interventions
DRUGdocetaxel
DRUGgemcitabine
DRUGbevacizumab
Sponsors
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The following information on clinical trials is provided for information purposes only to allow patients and physicians to have an initial discussion about the trial. This information is not intended to be complete information about the trial, to contain all considerations that may be relevant to potential participation in the trial, or to replace the advice of a personal physician or health professional. Inclusion Criteria: 1. 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); 2. 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 3. No previous systemic chemotherapy 4. Estimated life expectancy of \>/= 12 weeks 5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2 6. 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) 7. 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); 8. 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) 9. 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
1. 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) 2. Subjects with cardiovascular diseases and related treatments 3. 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; 4. Serious non-healing wound, ulcer, or bone fracture; 5. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study registration; 6. History of gross hemoptysis (defined as bright red blood of \>/= 0.5 teaspoon) 7. History of hypersensitivity reaction to drugs formulated with polysorbate 80; 8. Subjects with brain metastases; 9. Peripheral neuropathy \>/= Grade 2 (based on Common Toxicity Criteria Adverse Event \[CTCAE\] v3.0); 10. 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; 11. 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) 12. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel, Gemcitabine and Bevacizumab Combination therapy administered as follows: gemcitabine 1000 mg/m2 IV over 0.5 hour on Days 1 and 8; docetaxel 75 mg/m2 IV over 1 hour on Day 8; and bevacizumab 15 mg/kg IV on Day 1. Maintenance bevacizumab therapy was administered as 15 mg/kg IV on Day 1. | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-up | Death | 12 |
| Follow-up | Lost to Follow-up | 1 |
| Follow-up | Withdrawal by Subject | 1 |
| Treatment Period | Adverse Event | 9 |
| Treatment Period | Disease Progression | 4 |
| Treatment Period | Physician Decision | 1 |
| Treatment Period | Sponsor decision to close study | 1 |
| Treatment Period | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Docetaxel, Gemcitabine and Bevacizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age Continuous | 64.1 years STANDARD_DEVIATION 11.74 |
| Body Surface Area (BSA) | 1.766 m² STANDARD_DEVIATION 0.1737 |
| Disease Stage at 1st diagnosis IA | 0 Participants |
| Disease Stage at 1st diagnosis IB | 0 Participants |
| Disease Stage at 1st diagnosis IIA | 0 Participants |
| Disease Stage at 1st diagnosis IIB | 1 Participants |
| Disease Stage at 1st diagnosis IIIA | 0 Participants |
| Disease Stage at 1st diagnosis IIIB | 2 Participants |
| Disease Stage at 1st diagnosis IV | 14 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - Fully Active | 7 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 - Ambulatory, Restricted Activity | 8 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 - Ambulatory, No Work Activities | 2 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 3 - Limited Self Care, Partly Confined To Bed | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 4 - Completely Disabled, No Self Care | 0 Participants |
| Histopathological Grade G1 (well differentiated) | 1 Participants |
| Histopathological Grade G2 (moderately differentiated) | 3 Participants |
| Histopathological Grade G3 (poorly differentiated) | 3 Participants |
| Histopathological Grade G4 (undifferentiated) | 1 Participants |
| Histopathological Grade Unknown | 9 Participants |
| Region of Enrollment USA | 17 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 6 Participants |
| Tumor Histology Adenocarcinoma | 15 Participants |
| Tumor Histology Bronchoalveolar Cell | 1 Participants |
| Tumor Histology Large Cell | 1 Participants |
| Weight | 68.22 kg STANDARD_DEVIATION 12.648 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 17 |
| serious Total, serious adverse events | 9 / 17 |
Outcome results
Primary
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
Time frame: 1 year post-registration
Population: Due to early termination of the study only 17/90 subjects enrolled. Efficacy analysis of Progression Free Survival and Overall Survival were not performed. Efficacy results limited to a descriptive summary of best overall response for each subject.
Secondary
Objective Response Rate (Complete Response [CR] Plus Partial Response [PR]) Using Response Evaluation Criteria in Solid Tumors (RECIST)
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.
Time frame: 1 year from start of treatment
Population: Due to early termination of the study only 17/90 subjects enrolled. Efficacy analysis of Progression Free Survival and Overall Survival were not performed. Efficacy results limited to a descriptive summary of best overall response for each subject.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Docetaxel, Gemcitabine and Bevacizumab | Objective Response Rate (Complete Response [CR] Plus Partial Response [PR]) Using Response Evaluation Criteria in Solid Tumors (RECIST) | Complete Response | 0 Participants |
| Docetaxel, Gemcitabine and Bevacizumab | Objective Response Rate (Complete Response [CR] Plus Partial Response [PR]) Using Response Evaluation Criteria in Solid Tumors (RECIST) | Confirmed Partial Response | 6 Participants |
| Docetaxel, Gemcitabine and Bevacizumab | Objective Response Rate (Complete Response [CR] Plus Partial Response [PR]) Using Response Evaluation Criteria in Solid Tumors (RECIST) | Unconfirmed Partial Response | 1 Participants |
| Docetaxel, Gemcitabine and Bevacizumab | Objective Response Rate (Complete Response [CR] Plus Partial Response [PR]) Using Response Evaluation Criteria in Solid Tumors (RECIST) | Stable Disease | 2 Participants |
| Docetaxel, Gemcitabine and Bevacizumab | Objective Response Rate (Complete Response [CR] Plus Partial Response [PR]) Using Response Evaluation Criteria in Solid Tumors (RECIST) | Progressive Disease | 7 Participants |
| Docetaxel, Gemcitabine and Bevacizumab | Objective Response Rate (Complete Response [CR] Plus Partial Response [PR]) Using Response Evaluation Criteria in Solid Tumors (RECIST) | Not Evaluable | 1 Participants |
Secondary
Overall Survival
Survival is defined as the time from the date of registration to the study to the date of death.
Time frame: 2 years post-registration
Population: Due to early termination of the study only 17/90 subjects enrolled. Efficacy analysis of Progression Free Survival and Overall Survival were not performed. Efficacy results limited to a descriptive summary of best overall response for each subject.