Clinical trial NCT00369070: A Phase 2 Trial of AMG 706 or Bevacizumab in Combination With Chemo for Advanced NSCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Advanced Non-squamous NSCLC
Keywords: AMG 706
Bevacizumab
Paclitaxel and Carboplatin
Randomized
Non-Small Cell Lung Cancer
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2006-08-29
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective tumor response rate
timeFrame: Response assessments will be obtained every 6 +/- 1 week until subjects develop disease progression.
Secondary outcomes:
measure: Duration of response
timeFrame: Time from first objective tumor response to disease progression or death, if the death was due to disease progression.
measure: Progression free survival
timeFrame: Number of days from randomization tot he date of radiological evidence of disease progression or death.
measure: Overall survival
timeFrame: Time from randomization to death.
measure: Pharmacokinetics of AMG 706 when administered with paclitaxel and carboplatin in Arms A and B
timeFrame: From randomization until disease progression or death.
measure: Safety and tolerability in the 3 arms
timeFrame: From randomization until disease progression or death.
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Blumenschein GR Jr, Kabbinavar F, Menon H, Mok TSK, Stephenson J, Beck JT, Lakshmaiah K, Reckamp K, Hei YJ, Kracht K, Sun YN, Sikorski R, Schwartzberg L; Motesanib NSCLC Phase II Study Investigators. A phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer. Ann Oncol. 2011 Sep;22(9):2057-2067. doi: 10.1093/annonc/mdq731. Epub 2011 Feb 14.
citation: Claret L, Lu JF, Bruno R, Hsu CP, Hei YJ, Sun YN. Simulations using a drug-disease modeling framework and phase II data predict phase III survival outcome in first-line non-small-cell lung cancer. Clin Pharmacol Ther. 2012 Nov;92(5):631-4. doi: 10.1038/clpt.2012.78. Epub 2012 Aug 22.
citation: Bass MB, Yao B, Hei YJ, Ye Y, Davis GJ, Davis MT, Kaesdorf BA, Chan SS, Patterson SD. Challenges in developing a validated biomarker for angiogenesis inhibitors: the motesanib experience. PLoS One. 2014 Oct 14;9(10):e108048. doi: 10.1371/journal.pone.0108048. eCollection 2014.