A Study of the Safety, Tolerability, and Pharmacokinetics of MORAb-004, a Humanized Monoclonal Antibody, in Subjects With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Morphotek
- 入组人数
- 80
- 试验地点
- 3
- 主要终点
- To determine the safety of multiple intravenous infusions of MORAb-004
研究概览
简要总结
The purpose of this study is to determine the safety of multiple intravenous infusions of MORAb-004.
详细描述
MORAb-004 is a monoclonal antibody directed against endosialin, a cell surface glycoprotein, which is expressed on cells involved in tumor vasculature. Studies have found endosialin to play a key role in tumor growth and neovessel formation in numerous cancer types including (but not limited to) renal, breast, colon, pancreatic, lung, endometrial, ovarian, melanoma, sarcoma, and neuroectodermal tumors. Preclinical pharmacological studies have shown that MORAb-004 is a potentially useful anti-cancer agent. This clinical trial is being performed to determine the safety of MORAb-004 in subjects with solid tumors, as well as to establish serum pharmacokinetics of the antibody, and to assess tumor antigens that may serve as predictors of a response to MORAb-004. Study Part 2 was added to enroll subjects with specific histological diagnoses (colorectal cancer and soft tissue sarcoma) to further characterize the safety and tolerability of 5 dose levels of MORAb-004 previously tested during the dose escalation in Part 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Subjects ≥18 years of age.
- •Subjects with any malignant solid tumor without intracranial involvement or metastases diagnosed by standard pathology criteria that has failed standard chemotherapy.
- •Subject must have disease, as defined by RECIST or evaluable by clinical signs/symptoms (e.g., ascites, pleural effusion, or lesions of less than 2 cm) supported by biomarker, radiologic, or pathologic studies conducted within 4 weeks prior to study entry.
- •Karnofsky performance status ≥70%.
- •Female subjects of childbearing potential and all male subjects must consent to use a medically acceptable method of contraception throughout the study period and for 30 days after MORAb-004 administration. A barrier method of contraception must be included.
- •Laboratory and clinical results within the 2 weeks prior to Study Day 1 as follows: Absolute neutrophil count (ANC) ≥1.5 x 109/L; Platelet count ≥100 x 109/L; Hemoglobin ≥10 g/dL; Serum bilirubin ≤2.0 mg/dL; Aspartate transaminase (AST) ≤2.5 x ULN; or ≤5 x ULN if liver metastases are present; Alanine transaminase (ALT) ≤2.5 x ULN; or ≤5 x ULN if liver metastases are present; Serum creatinine ≤2.0 mg/dL; prothrombin time (PT) and aPTT within institutional limits of normal.
- •Subject must be willing and able to provide written informed consent.
- •In Part 2 (expansion cohorts) ONLY, subjects must have a histological diagnosis of either CRC or STS (and subtypes, excluding bone sarcomas).
排除标准
- •Known central nervous system (CNS) tumor involvement or metastases.
- •Evidence of other active malignancy.
- •Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class III or IV, angina not well controlled by medication, or myocardial infarction within 6 months).
- •Electrocardiogram (ECG) demonstrating clinically significant arrhythmias (Note: Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal SVT, are eligible).
- •Presence of severe lung disease (In the absence of clinically apparent severe lung disease, no formal testing is necessary. In the presence of clinically severe lung disease, FEV1 must be >60% in order for the subject to be eligible.)
- •Active serious systemic disease, including active bacterial or fungal infection.
- •Chronic inflammatory disorder, e.g., inflammatory bowel disease, active vasculitis.
- •Chemotherapy, biologic therapy, or immunotherapy within 3 weeks prior to enrollment.
- •Breast-feeding, pregnant, or likely to become pregnant during the study.
- •Active hepatitis or human immunodeficiency virus (HIV) infection.
- •Subjects who have received a previous monoclonal antibody therapy and have evidence of an immune or allergic reaction, or previously documented human anti-human antibody (HAHA).
- •Subjects with large ascites or pleural effusion (≥500 cc) based on results of most recent CT scan).
- •Chronic systemic anticoagulation therapy with warfarin or heparin
研究组 & 干预措施
MORAb-004
干预措施: MORAb-004 (monoclonal antibody to TEM1) (Drug)
结局指标
主要结局
To determine the safety of multiple intravenous infusions of MORAb-004
时间窗: Weekly while receiving study drug
Safety is evaluated by clinical assessment, monitoring of adverse events, laboratory evaluations, ECG.
次要结局
- To detect any antibody response (human anti-human antibodies [HAHA] to multiple intravenous infusions of MORAb-004(Biweekly)
- To determine optimal biologic dose (OBD) of MORAb-004(Weekly)
- To describe changes in the objective measurements of tumor size and biomarkers (if applicable)after treatment with MORAb-004(bimonthly)
- To determine the maximum tolerated dose (MTD) of MORAb-004 (within the administered range)(Weekly)
- To establish the serum pharmacokinetics of MORAb-004 using a validated assay(Weekly)