Phase 1b/2 Trial of AMG386 With Pemetrexed and Carboplatin in Non-Small Cell Lung Cancer

• Conditions: Metastatic Non-Squamous Non-Small Cell Lung Cancer; MedDRA version: 16.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-001111-31-BE
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06-12
• Last Update Posted: 14 March 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 217

Inclusion Criteria

Disease related
• Histologically confirmed (cytological specimens obtained by bronchial washing or brushing, or fine-needle aspiration are acceptable), unresectable stage IV non-squamous NSCLC
• Radiographically evaluable disease (measurable or non-measurable) per RECIST 1.1 with modifications (Appendix G)

General
• Men or women aged = 18 years old
• ECOG Performance Status of 0 or 1 (see Appendix J)
• Life expectancy = 3 months (per investigator opinion)
• Generally well-controlled blood pressure with systolic blood pressure = 140 mmHg AND diastolic blood pressure = 90 mmHg prior to enrolment or randomization. The use of anti-hypertensive medications to control hypertension is permitted

Laboratory
• Adequate organ and hematological function as evidenced by the
following laboratory studies

- Hematological function:
? Absolute neutrophil count (ANC) = 1.5 x 109/L
? Platelet count = 100 x 109/L and = 850 x 109/L
? Hemoglobin = 9 g/dL

- Coagulation function:
? partial thromboplastin time (PTT) or activated prothrombin
time (aPTT) = 1.5 x ULN per institutional laboratory range
? International normalized ratio (INR) = 1.5

- Renal function:
? Urinary protein of = 30 mg/dL in urinalysis or = 1+ on dipstick,
unless quantitative protein is = 1000 mg in a 24-hour urine
sample
? Creatinine clearance (CrCl) = 45 mL/min per 24-hour urine
collection or calculated according to the Cockcroft-Gault formula:

CrCl (mL/min) =
(140-age) x actual body weight (kg)
(x 0.85) for females
72 x serum creatinine (mg/dL)

- Or

CrCl (mL/min) =
(140-age) x actual body weight (kg)
(x 0.85) for females
0.8136 x serum creatinine (µmol/L)

- Hepatic function:
? AST and ALT = 2.5 x ULN per institutional laboratory range
(or= 5 x ULN if liver metastases are present)
? Total bilirubin < 1.2 mg/dL

- Nutritional:
? Albumin = 2.8 g/dL
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 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 87

Exclusion Criteria

• Any prior chemotherapy or targeted therapy for non-squamous NSCLC
• Subjects with adenosquamous histology or any histology subtype containing greater than 10% squamous cells
• Subjects with a known epidermal growth factor receptor (EGFR)
mutation sensitive to treatment with a tyrosine kinase inhibitor (TKI)
• Subjects with known anaplastic lymphoma kinase (EML4-ALK)
translocations
• History or presence of central nervous system metastases.
Central (chest) radiation therapy within 28 days, or radiation therapy to any other site within 14 days prior to enrollment/ randomization.
• Subjects must have recovered from all radiotherapy related toxicity
- If all sites of disease have been irradiated, documented progression must have occurred in at least 1 site of disease subsequent to the radiation therapy
• History of pulmonary hemorrhage or gross hemoptysis (approximately 3 mL of bright red blood or more) within 6 months prior to enrollment/randomization
• History of arterial or venous thromboembolism within 12 months prior to enrollment/randomization
• History of clinically significant bleeding within 6 months prior to
enrollment/randomization

Medications
• Enrolled in or has not yet completed a 30-day washout period prior to enrollment/randomization for an investigational device or drug trial, or is currently receiving other investigational treatment
• Known active or ongoing infection (except uncomplicated urinary tract infection) within 14 days prior to enrollment/randomization
• Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
• Treatment within 30 days prior to enrollment/randomization with
strong immune modulators including but not limited to systemic cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, methotrexate, azathioprine, rapamycin, thalidomide, and lenalidomide

General Medical
• Clinically significant cardiovascular disease within 12 months prior to enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, or placement of percutaneous transluminal coronary angioplasty/stent
• History of prior malignancy, except:
- Malignancy treated with curative intent and with no known active
disease present for = 3 years before enrollment/randomization and felt to be at low risk for recurrence by the treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna
without evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of
disease
- Prostatic intraepithelial neoplasia without evidence of prostate cancer
• Major surgery within 28 days prior to enrollment/randomization or still recovering from prior surgery
• Minor surgical procedures, except placement of tunneled central
venous access device within 3 days prior to enrollment/ randomization
• History of allergic reactions to bacterially produced proteins
• Pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding or planning to become pregnant within 6 months after the end of treatment
• Subject not willing to use highly effective methods of birth control during treatment and for 6 months after the end of treatment
• Known positive test(s) for human immunodeficiency virus (HIV)
infection, hepatitis C

Study & Design

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