A Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Trialof AMG 706 in Combination With Paclitaxel and Carboplatin for AdvancedNon-small Cell Lung Cancer

• Conditions: Subjects with unresectable stage IIIB with pericardial or pleural effusion or stage IV or recurrent Non Small Cell Lung Cancer (NSCLC); MedDRA version: 16.0Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 16.0Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 16.0Level: PTClassification code 10029515Term: Non-small cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2006-003784-32-IE
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03-08
• Last Update Posted: 15 July 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1400

Inclusion Criteria

• Histologically confirmed (cytological specimens obtained by bronchial washing or
brushing, or fine-needle aspiration are acceptable), unresectable stage IIIB with
pericardial or pleural effusion or stage IV or recurrent non-squamous NSCLC. Evaluation of effusions (ie, with cytology) is not required if diagnosis of non-squamous NSCLC has been otherwise histologically confirmed.

• Measurable or non-measurable disease per modified RECIST criteria
• ECOG performance status of 0 or 1
• Life expectancy of = 3 months as documented by the investigator.

• Men or women aged = 18 years old.

• Hematological function, as follows:

- Absolute neutrophil count (ANC) = 1.5 x 109/L

- Platelet count = 100 x 109/L and = 850 x 109/L

- Hemoglobin = 9 g/dL

• Renal function, as follows:

- Creatinine clearance (GFR)> 40 mL/min (calculated by Cockcroft-Gault formula)

- Urinary protein quantitative value of = 30 mg in urinalysis or = 1+ on dipstick unless quantitative protein is < 500 mg in a 24-hour urine sample

• Hepatic function, as follows:

- Aspartate aminotransferase (AST) = 2.5 x upper limit of normal (ULN) OR
AST < 5 x ULN if liver metastases are present

- Alanine aminotransferase (ALT) = 2.5 x ULN OR ALT < 5 x ULN if liver metastases are present

- Alkaline phosphatase = 2.0 x ULN OR alkaline phosphatase < 5 x ULN if liver or bone metastases are present

- Total bilirubin < 1.5 x ULN OR total bilirubin < 3 X ULN if subject has UGT1A1 promoter polymorphism (ie, Gilbert syndrome) confirmed by genotyping or Invader® UGT1A1 Molecular Assay prior to randomization

• Partial thromboplastin (PTT) or activated partial thromboplastin (aPTT)

= 1 x ULN and international normalized ratio (INR) = 1.5 x ULN.

• Competency to give written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Subjects with adenosquamous histology or an unclear histology subtype
(eg, not otherwise specified) containing greater than 10% squamous cells
• Untreated or symptomatic central nervous system metastases. Subjects with a
history of brain metastases are eligible if definitive therapy has been administered (surgery and/or radiation therapy), there is no planned treatment for brain metastases, and the subject is clinically stable and is off corticosteroids for at least 2 weeks prior to randomization.
• Prior chemotherapy as follows:
- Any prior chemotherapy for advanced non-squamous NSCLC
- Any prior adjuvant chemotherapy for non-squamous NSCLC within
52 weeks prior to randomization. Adjuvant chemotherapy completed
> 52 weeks prior to randomization is permitted
- Any prior chemoradiation for locally advanced stage III disease
• Central (chest) radiation therapy within 28 days prior to randomization, radiation
therapy within 14 days prior to randomization for peripheral lesions.
• History of pulmonary hemorrhage or gross hemoptysis (approximately 3 mL of bright red blood or more) within 6 months prior to randomization.
• Prior targeted therapies, including but not limited to:
- AMG 706, inhibitors of VEGF (eg, SU5416, SU6668, ZD6474, SU11248, PTK787, AZD2171, AEE-788, sorafenib, bevacizumab), or EGFr (eg, panitumumab, cetuximab, gefitinib, erlotinib).
• Known history of allergy or hypersensitivity reaction to paclitaxel or carboplatin.
• Any anticoagulation therapy within 7 days prior to randomization. The use of low-dose warfarin [= 2 mg daily] or low molecular weight heparin or heparin flushes for prophylaxis against central venous catheter thrombosis is allowed.

General
• Prior (within 30 days of randomization) yellow fever vaccination
• History of arterial or venous thrombosis within 12 months prior to randomization.
• History of bleeding diathesis or bleeding within 14 days prior to randomization.
• Peripheral neuropathy > grade 1 per Common Terminology Criteria for Adverse
Events (CTCAE) Version 3.0.
• Clinically significant cardiac disease within 12 months of randomization, including
myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, percutaneous transluminal coronary angioplasty/stent, congestive heart failure, or ongoing arrhythmias requiring medication.
• History of other primary cancer unless:
o Curatively resected non-melanomatous skin cancer
o Curatively treated cervical carcinoma in situ
o Other primary solid tumor curatively treated with no known active disease
present and no curative treatment administered for the last 3 years
• Any kind of disorder that compromises the ability of the subject to comply with
the study procedures.
• Open wound, ulcer or fracture.
• Uncontrolled hypertension as defined by resting blood pressure > 150/90 mm Hg.
Antihypertensive medications are allowed if the subject is stable on their current
dose at the time of randomization.
• Surgery:
- Major surgical procedures within 28 days prior to randomization
- Minor surgical procedures within 14 days prior to randomization
- Failure to recover from prior surgery
- Placement of a central venous access device (including ports and tunneled or non-tunneled catheters) within 7 days prior to randomization
- Planned elective surgery while on study treatment
- Core needle biopsy within 7 days prior to randomization
• Not recovered from all previous therapies (ie, rad

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified