A Phase 2 Trial of AMG 706 or Bevacizumab in Combination With Chemo for Advanced NSCLC

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Multicenter, Open Label, Randomized Trial of AMG 706 or Bevacizumab in Combination With Paclitaxel and Carboplatin for Advanced Non-squamous Non-small Cell Lung Cancer

Conditions
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Advanced Non-squamous NSCLC

Intervention / Treatment
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* Biological: Bevacizumab
* Drug: AMG 706
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>AMG 706 125 mg once daily (QD) and paclitaxel and carboplatin chemotherapy regimen (paclitaxel 200 mg/m2 and carboplatin at AUC of 6 mg/mL x min) on day 1 of each 3 week cycle for a maximum of 6 cycles. | Drug: AMG 706<br>* 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<br>* Other names: Motesanib diphosphate;Drug: Paclitaxel<br>* 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.<br>Drug: Carboplatin<br>* 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.<br>|
| Experimental: B<br>AMG 706 75 mg twice daily every 12 ± approximately 1 hour for 5 days followed by a 2 day treatment free period every 7 days and paclitaxel and carboplatin chemotherapy regimen (paclitaxel 200 mg/m2 and carboplatin at AUC of 6 mg/mL x min) on day 1 of each 3 week cycle for a maximum of 6 cycles. | Drug: AMG 706<br>* 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<br>* Other names: Motesanib diphosphate;Drug: Paclitaxel<br>* 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.<br>Drug: Carboplatin<br>* 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.<br>|
| Active Comparator: C<br>Bevacizumab 15 mg/kg bevacizumab, delivered via intravenous (IV) infusion once every 3 weeks and paclitaxel and carboplatin chemotherapy regimen (paclitaxel 200 mg/m2 and carboplatin at AUC of 6 mg/mL x min) on day 1 of each 3 week cycle for a maximum of 6 cycles. | Biological: Bevacizumab<br>* 15 mg/kg bevacizumab, delivered via intravenous (IV) infusion once every 3 weeks<br>* Other names: Avastin;Drug: Paclitaxel<br>* 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.<br>Drug: Carboplatin<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response rate |  | Response assessments will be obtained every 6 +/- 1 week until subjects develop disease progression. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMG 706, Bevacizumab, Paclitaxel and Carboplatin, Randomized, Non-Small Cell Lung Cancer