A Multicenter, Open Label, Randomized Study of AMG 951 in Subjects with Previously Untreated Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC) Treated with Chemotherapy with or without Bevacizumab

Conditions: Subjects with Previously Untreated Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC) Treated with Chemotherapy with or without Bevacizumab
MedDRA version: 9.1Level: LLTClassification code 10029522Term: Non-small cell lung cancer stage IV
MedDRA version: 9.1Level: LLTClassification code 10029521Term: Non-small cell lung cancer stage IIIB

Registration Number: EUCTR2005-005484-28-PL

Lead Sponsor: Amgen Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 200

Inclusion Criteria

Disease related
-Histologically or cytologically confirmed Non-Small Cell Lung Cancer (NSCLC).
Mixed tumors will be categorized by the predominant cell type unless small cell
elements are present in which case the patient is ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy.
-Subjects must have advanced NSCLC defined as stage IIIb with malignant pleural effusion or Stage IV or recurrent disease. Disease must be measurable to be included in the phase 2 study
-Planning to receive up to 6 cycles of chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (see
Appendix F)
• Life expectancy greater than 3 months

Demographic:
• =18 years old and of legal age for informed consent
• Subjects must sign and date a written Independent Ethics Committee (IEC)-
approved Informed Consent Form

Laboratory
• INR = 1.2 and PTT = ULN within 1 week prior to enrollment
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

Disease Related:
-Prior malignancy other than NSCLC (except in situ basal cell carcinoma or in situ
cervical cancer), unless have been treated with curative intent with no evidence of disease for =3yrs
-Untreated or unstable central nervous system (CNS) metastases. Subjects with treated and stably controlled CNS metastases are eligible for cohorts A&B of the phase 2 part of the study 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 or on a stable dose of corticosteroids for at least 2 wks prior to enrollment
-Myocardial infarction, or unstable or uncontrolled disease or condition related to
or impacting cardiac function (e.g., unstable angina, congestive heart failure [New York Heart Association >class II]) within 1 yr of enrollment
-Uncontrolled hypertension defined as: systolic blood pressure =150 mm Hg OR
diastolic blood pressure =100mm Hg (antihypertensive therapy to achieve these
parameters is allowable)
-History of arterial thrombosis, pulmonary embolus, deep vein thrombosis or hemorrhagic disorders within 1 yr of enrollment
-Recent major surgical procedure within 28 days of enrollment
-Subjects must not have serious non-healing wound ulcer, or bone fracture within
21 days prior to enrollment
-Persistent history of gross hemoptysis (defined as bright red blood of a ½teaspoon or more) relating to subject’s NSCLC
-Known (documented in medical notes) HIV infection
-Active infection on day of enrollment
-Known to be hepatitis C positive OR hepatitis B surface antigen positive
-Subjects with Gilbert’s syndrome
Laboratory:
-Absolute neutrophil count (ANC) <1.5 x 109 /L (without granulocyte-colony stimulating factor support within 2 wks of enrollment)
-Platelet count <100 x 109 /L (without transfusion within 2 wks of enrollment)
-Hemoglobin <9 g/dL (subjects may be transfused or receive erythropoietic treatment to meet criterion)
-Urine protein quantitative value of >1+ on dipstick or =30 mg/dL in urinalysis. If quantitative protein is <500 mg in 24hr urine collection then subject can be included
-Significant liver dysfunction as defined by aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 x upper limits of normal (ULN)
-Alkaline phosphatase >2.5 x ULN, or alkaline phosphatase >5 x ULN in the presence of bone or liver metastasis
-Total bilirubin >1.5 X ULN
-Calculated creatinine clearance <50mL/min.
-Hypercalcemia (serum calcium =12.0 mg/dL or symptomatic)
Medication:
-Prior chemotherapy (except for adjuvant chemotherapy, provided the last dose of adjuvant therapy was received at least one year prior to enrollment), hormonal therapy, radiotherapy (except palliative radiotherapy for bone metastases or radiation therapy for CNS metastases) or immunotherapy for treatment of advanced NSCLC
-Prior drug treatment or therapy with investigational agents for NSCLC
-Therapeutic anticoagulation treatment. Prophylactic anticoagulation of venous access devices (e.g., with low-dose warfarin [1-2 mg/day] or lowdose heparin) is allowed providing INR =1.2 and PTT =ULN within 1 wk prior to randomization
-Chronic daily treatment with aspirin (>325 mg/day) or non-steroidal antiinflammatory agents known to inhibit platelet function. Treatment with
dipyridamole, ticlopidine, clopidogrel and/or cilostazol is also not allowed
General:
-Participation in clinical trials or undergoing other inves

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Phase 2 Primary Objective: <br>To evaluate the objective response rate (CR and PR) by modified RECIST for AMG 951 at varying dose schedules in combination with carboplatin / paclitaxel + bevacizumab for subjects with NSCLC.;Secondary Objective: Phase 2 Secondary Objectives: <br>To evaluate overall response rate (CR, PR and SD), progression-free survival, time to response, duration of response, time to progression and overall survival for AMG 951 at varying dose schedules. <br><br>To evaluate the safety profile of AMG 951 at varying dose schedules.<br><br>To evaluate the formation of anti-AMG 951 antibodies.;Primary end point(s): Objective response rate (complete or partial response) (Phase 2)<br>

Secondary Outcome Measures

Name	Time	Method

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