NCT00562380已完成1 期
A Phase 1, Open-Label, Dose Finding Study Evaluating the Safety and Pharmacokinetics of AMG 479 in Subjects With Advanced Solid Tumors
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- Safety
研究概览
简要总结
RATIONALE: Monoclonal antibodies, such as AMG-479, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.
PURPOSE: This phase I trial is studying the side effects and best dose of AMG-479 in treating patients with advanced solid tumors or non-Hodgkin lymphoma.
详细描述
OBJECTIVES:
Primary
- To assess the safety and pharmacokinetics of anti-IGF-1R fully human monoclonal antibody AMG-479 (AMG-479) after multiple intravenous administrations in adult patients with histologically documented advanced solid tumors that are refractory to standard therapy or for which no curative therapy is available.
Secondary
- To assess the tolerability and to determine the maximum tolerated dose of AMG-479.
- To assess tumor glucose metabolism using PET/CT scanning with the tracer fludeoxyglucose F 18.
- To measure insulin-like growth factor receptor (IGF-1R) levels on peripheral blood cells.
- To establish whether human anti-human antibodies to AMG-479 develop in patients with advanced solid tumors.
- To measure the tumor response by modified Response Evaluation Criteria in Solid Tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Inclusion criteria:
- •Histologically or cytologically confirmed advanced solid tumors or non-Hodgkin lymphoma that is refractory to standard treatment or for which no curative therapy is available
- •Tumor tissue that is accessible for biopsy by using minimally invasive procedures and must consent to undergo biopsies of the tumor (part 2)
- •Exception for patients with Ewing family tumors or desmoplastic small round cell tumors whose anatomic location would pose an increase in the risk of injury due to biopsy (i.e., bleeding or pneumothorax)
- •Willing to provide existing and/or future paraffin-embedded tumor samples
排除标准
- •Primary CNS tumors or hematological malignancies, other than non-Hodgkin lymphoma
- •Primary hepatic tumors or at increased risk for hepatic tumors, including any of the following:
- •Hepatitis of any etiology
- •Alcohol abuse or dependency
- •Hepatic adenoma
- •Follicular nodular hyperplasia
- •Autoimmune conditions associated with biliary tract cancer
- •Alpha 1 antitrypsin deficiency
- •Hemochromatosis
- •History of vinyl chloride or thorotrast/thorium dioxide exposure
- •History of histiocytic (Kupffer cell) neoplasia
- •Presence of untreated or symptomatic CNS metastases or symptoms of brain metastases
- •Presence of ascites or pleural effusion requiring medical intervention
- •PATIENT CHARACTERISTICS:
- •Inclusion criteria:
- •ECOG performance status ≤ 2
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •Able to provide fasting blood samples for triglyceride and glucose laboratory tests
- •Able to fast for 4-6 hours for fludeoxyglucose F18-PET/CT scan
- •Controlled type 1 or 2 diabetes (defined as hemoglobin A1c < 8.0% and fasting blood glucose level < 160 mg/dL) allowed for part 2 only
- •Exclusion criteria:
- •History of clinically significant hypoglycemia or hyperglycemia (in the opinion of the investigator)
- •Myocardial infarction within the past year
- •Unstable or uncontrolled disease/condition related to or impacting cardiac function, including any of the following:
- •Unstable angina
- •Congestive heart failure
- •NYHA class III or IV heart disease
- •Uncontrolled hypertension (diastolic BP > 90 mm Hg and systolic BP > 150 mm Hg)
- •Clinically significant cardiac arrhythmia
- •CTCAE version 3.0 ≥ grade 2
- •Clinically significant electrocardiogram abnormalities
- •History of arterial or venous (deep vein) thrombosis within the past year
- •History of bleeding diathesis
- •History of chronic hepatitis
- •History of HIV infection
- •Unable to tolerate intravenous administration
- •Known sensitivity to mammalian-derived products
- •ANC < 1,500/mm^3 (without filgrastim [G-CSF] support within the past 2 weeks)
- •Platelet count < 100,000/mm^3 (without transfusion within the past 2 weeks)
- •Hemoglobin < 9 g/dL (without transfusion within the past 4 weeks)
- •PT/PTT > 1.5 x upper limit of normal (ULN)
- •Serum creatinine > 1.5 x ULN
- •AST and ALT > 2.5 x ULN
- •Total bilirubin > 1.5 x ULN
- •Urinary protein excretion > 1,000 mg/day (≥ 2+ using dipstick analysis)
- •Any kind of disorder that compromises the ability of the patient to give written informed consent and/or comply with study procedures
- •Any comorbid medical condition, that in the sponsor's or investigator's opinion, may put the patients at significant risk
- •Known sensitivity to any of the products to be administered during dosing
- •Unresolved toxicities > grade 1 from prior anticancer therapy, excluding alopecia
- 另有 13 项未显示
结局指标
主要结局
Safety
Pharmacokinetic profile
次要结局
- Tumor glucose metabolism as measured by fludeoxyglucose F 18-PET/CT scan
- Levels of cross-linked c-telopeptides of type 1 collagen and bone-specific alkaline phosphatase (may also include tartrate-resistant acid phosphatase 5b) in blood
- Anti-AMG-479 antibody formation
- The incidence of dose-limiting toxicities and the severity of adverse events
- Tumor response measured by modified RECIST
- Level of insulin-like growth factor receptor-1 (IGF-1R) on peripheral blood cells
- Circulating levels of IGF-1R and IGF-BP3
研究者
研究点 (2)
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