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

Phase 1

• Conditions: Subjects with unresectable stage IIIB with pericardial or pleural effusion or stage IV or recurrent Non Small Cell Lung Cancer (NSCLC); MedDRA version: 9.1Level: LLTClassification code 10029521Term: Non-small cell lung cancer stage IIIB; MedDRA version: 9.1Level: LLTClassification code 10029515Term: Non-small cell lung cancer recurrent; MedDRA version: 9.1Level: LLTClassification code 10029522Term: Non-small cell lung cancer stage IV

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-04-10
• Last Update Posted: 13 March 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1240

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 NSCLC. Evaluation of
effusions (ie, with cytology) is not required if diagnosis of 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 > 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) = 1 x ULN and international normalized ratio (INR)
= 1.5 x ULN.
• Ability to take oral medications.
• Competency to give written informed consent.
• Able to start protocol directed therapy within 7 days from date of randomization.
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

• 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 NSCLC
- Any prior adjuvant chemotherapy for 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, 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.
• 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, radiation, surgery and medications). Adverse events related to previous therapies must be CTCAE grade = 1 at screening or returned to the subject’s baseline prior to their most recent previous therapy.
• Participation in therapeutic clinical trials or currently r

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine if treatment with AMG 706 in combination with paclitaxel and carboplatin improves overall survival compared to treatment with placebo in combination with paclitaxel and carboplatin in subjects with advanced NSCLC.;Secondary Objective: • To evaluate progression-free-survival time, objective tumor response rate (only in<br>subjects with measurable disease) and duration of response.<br>• To evaluate the safety and tolerability of AMG 706 in combination with paclitaxel<br>and carboplatin compared to placebo in combination with paclitaxel and carboplatin.<br>• To evaluate the pharmacokinetics (Cmin and Cmax) of AMG 706 when administered<br>with paclitaxel and carboplatin (in approximately 250 subjects at selected centers).<br><br>;Primary end point(s): Overall survival time: Time from randomization to death. Subjects who have not died<br>while on study or are lost to follow-up will be censored at their last contact date.