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

Phase 2

Terminated

• Conditions: Advanced Non-squamous NSCLC
• Interventions: Biological: Bevacizumab; Drug: AMG 706; Drug: Paclitaxel; Drug: Carboplatin

• Registration Number: NCT00369070
• Lead Sponsor: Amgen

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2006-08-24
• Study First Submitted QC: 2006-08-24
• Study First Posted: 2006-08-29
• Study Start: 2007-01-31
• Primary Completion: 2008-04-23
• Study Completion: 2011-08-03
• Disposition First Submitted: 2015-12-14
• Disposition First Submitted QC: 2015-12-14
• Disposition First Posted: 2016-01-14
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-02
• Last Update Posted: 2018-01-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 186

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
C	Bevacizumab	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.
A	AMG 706	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.
B	AMG 706	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.
C	Carboplatin	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.
A	Carboplatin	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.
A	Paclitaxel	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.
B	Paclitaxel	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.
B	Carboplatin	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.
C	Paclitaxel	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.

Primary Outcome Measures

Name	Time	Method
Objective tumor response rate	Response assessments will be obtained every 6 +/- 1 week until subjects develop disease progression.

Secondary Outcome Measures

Name	Time	Method
Duration of response	Time from first objective tumor response to disease progression or death, if the death was due to disease progression.
Pharmacokinetics of AMG 706 when administered with paclitaxel and carboplatin in Arms A and B	From randomization until disease progression or death.
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.
Safety and tolerability in the 3 arms	From randomization until disease progression or death.