An Open Label Phase 1B Dose-Escalation Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 38
- 试验地点
- 4
- 主要终点
- Determine Maximum Tolerated Dose of TRC105 in Combination With Bevacizumab
研究概览
简要总结
The purpose of the study is to evaluate safety and tolerability and determine a recommended Phase 2 dose for TRC105 when added to standard dose bevacizumab in patients with advanced solid tumors for which bevacizumab is indicated.
详细描述
Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) that inhibits angiogenesis and extends survival in patients with a wide variety of solid tumor types. TRC105, a monoclonal antibody to CD105, is a novel angiogenesis inhibitor that complements bevacizumab in preclinical models. Together, these antibodies may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with bevacizumab alone. The purpose of the study is to evaluate safety and tolerability and determine a recommended Phase 2 dose for TRC105 when added to standard dose bevacizumab in patients with advanced solid tumors for which bevacizumab is indicated.
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
- •Histologically proven advanced or metastatic solid cancer
- •Measurable disease, evaluable disease or elevation of a relevant soluble tumor marker (e.g., CEA, PSA, CA125)
- •Age of 18 years or older
- •ECOG performance status of 0 or 1
- •Resolution of all acute AEs resulting from prior cancer therapies to NCI CTCAE Grade ≤ 1 or baseline (except alopecia)
- •Adequate organ function
- •Willing and able to consent for self to participate in study
排除标准
- •Prior treatment with TRC105
- •Serious dose-limiting toxicity related to prior bevacizumab
- •Current treatment on another therapeutic clinical trial
- •Receipt of an investigational agent within 28 days of starting study treatment
- •Prior surgery (including open biopsy) within 28 days of starting the study treatment
- •Prior radiation therapy or systemic therapy within 21 days of starting the study treatment
- •Minor surgical procedures such as fine needle aspirations, Mediport placement or core biopsies within 7 days of study treatment
- •Uncontrolled chronic hypertension defined as systolic > 140 or diastolic > 90 despite optimal therapy (initiation or adjustment of BP medication prior to study entry allowed provided that the average of 3 BP readings at a visit prior to enrollment is < 140/90 mm Hg)
- •Symptomatic pericardial or pleural effusions
- •Uncontrolled peritoneal effusions requiring paracentesis more frequently than every 2 weeks
- •History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease (except in the expansion cohort at the MTD where brain metastases or primary brain tumors are eligible)
- •Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, DVT, PTCA or CABG within the past 6 months
- •Active bleeding or pathologic condition that carries a high risk of bleeding
- •Thrombolytic or anticoagulant use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
- •Cardiac dysrhythmias of NCI CTCAE Grade ≥ 2 within the last 28 days
- •Known active viral or nonviral hepatitis
- •Centrally located non-small cell lung cancer (regardless of histologic sub-type), or non-small cell lung cancer of squamous histology.
- •History of hemorrhage or hemoptysis (>½ teaspoon bright red blood) within 6 months of starting study treatment
- •Open wounds or unhealed fractures within 28 days of starting study treatment
- •History of peptic ulcer disease or erosive gastritis within the past 6 months, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment
- •Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
- •Pregnancy or breastfeeding
研究组 & 干预措施
TRC105 and Bevacizumab
Escalating doses of i.v. TRC105 will be administered weekly beginning with 3 mg/kg in combination with 15 mg/kg bevacizumab given every 3 weeks. Patients will receive TRC105 treatment on Days 1, 8, and 15 and bevacizumab treatment on Day 1 of each 21-day cycle.
干预措施: TRC105 and Bevacizumab (Drug)
结局指标
主要结局
Determine Maximum Tolerated Dose of TRC105 in Combination With Bevacizumab
时间窗: 1.5 years
Three patients will be initially enrolled and treated at each dose level. If none of these 3 patients experiences a dose-limiting toxicity (DLT) during the 28-day evaluation period, dose escalation will proceed following review of safety data with appropriate site staff including the principal investigators at all sites. If 1 of 3 patients experiences DLT, the cohort will be expanded to 6 patients. The maximum tolerated dose (MTD) will have been exceeded if ≥ 33% of patients experience DLT in a given cohort. DLT will have occurred when a patient has 1 or more toxicity listed in the table below that is at least possibly related to the combination of bevacizumab and TRC105 during the first 28 days (cycle 1).
次要结局
- Objective Response According to RECIST 1.1(1.5 years)
- Immune Response to TRC105(1.5 years)
- TRC105 Pharmacokinetic Concentrations(1.5 years)