Advanced Non-squamous NSCLC
Conditions
Keywords
AMG 706, Bevacizumab, Paclitaxel and Carboplatin, Randomized, Non-Small Cell Lung Cancer
Brief summary
The purpose of this study is to estimate the difference in objective response rates between each paclitaxel/carboplatin plus AMG 706 arm (Arm A and B) and paclitaxel/carboplatin plus bevacizumab arm (Arm C) in subjects with advanced non-squamous NSCLC.
Interventions
BIOLOGICALBevacizumab
15 mg/kg bevacizumab, delivered via intravenous (IV) infusion once every 3 weeks
DRUGAMG 706
subjects in Arms A and B will take AMG 706 orally in one of two dosing regimens over each 21-day cycle: •Arm A: 125 mg once daily (QD) •Arm B: 75 mg twice daily every 12 ± approximately 1 hour for 5 days followed by a 2 day treatment free period every 7 days
DRUGPaclitaxel
All subjects will receive a paclitaxel chemotherapy regimen (paclitaxel 200 mg/m2) on day 1 of each 3-week cycle for a maximum of 6 cycles.
DRUGCarboplatin
All subjects will receive carboplatin chemotherapy regimen (carboplatin at AUC of 6 mg/mL x min) on day 1 of each 3-week cycle for a maximum of 6 cycles.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women 18 years or older with histologically or cytologically confirmed advanced non-squamous NSCLC (unresectable stage IIIB with pericardial or pleural effusion or stage IV/recurrent) * Measureable disease per RECIST criteria modified * ECOG performance status of 0 or 1 * Ability to take oral medications * Competent to give written informed consent
Exclusion criteria
* Current or prior history of CNS metastases * Any prior chemotherapy for advanced NSCLC * History of pulmonary hemorrhage or gross hemoptysis within 6 months prior to randomization * Prior targeted therapies * Known history of allergy or hypersensitivity to paclitaxel or carboplatin * History of arterial or venous thrombosis within 52 weeks prior to randomization * History of bleeding diathesis or non-pulmonary bleeding within 14 days prior to randomization * Peripheral neuropathy \> grade 1 per CTCAE Version 3.0 * Myocardial infarction, cerebrovascular accident, grade 2 or greater peripheral vascular disease, transient ischemic attack, congestive heart failure, percutaneous transluminal coronary angioplasty/stent, ongoing arrythmias requiring medication or unstable angina within 52 weeks prior to randomization * Any kind of disorder that compromises the ability of the subject to comply with the study procedures * Uncontrolled hypertension as defined by resting blood pressure \> 150/90 mm Hg. Anti-hypertensive medications are allowed if hypertension is stably controlled at the time of randomization. * Participation in therapeutic clinical trials or currently receiving other investigational treatment(s) within 30 days prior to randomization * Pregnant or breast feeding women * Known to be HIV, hepatitis B surface antigen, or hepatitis C positive
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective tumor response rate | Response assessments will be obtained every 6 +/- 1 week until subjects develop disease progression. |
Secondary
| Measure | Time frame |
|---|---|
| Duration of response | Time from first objective tumor response to disease progression or death, if the death was due to disease progression. |
| Progression free survival | Number of days from randomization tot he date of radiological evidence of disease progression or death. |
| Overall survival | Time from randomization to death. |
| Pharmacokinetics of AMG 706 when administered with paclitaxel and carboplatin in Arms A and B | From randomization until disease progression or death. |
| Safety and tolerability in the 3 arms | From randomization until disease progression or death. |
Outcome results
None listed