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Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors for Which Bevacizumab is Indicated

2018年11月7日 更新者:Tracon Pharmaceuticals Inc.

An Open Label Phase 1B Dose-Escalation Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors

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.

研究概览

地位

完全的

详细说明

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.

研究类型

介入性

注册 (实际的)

38

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • Alabama
      • Birmingham、Alabama、美国、35249
        • University of Alabama at Birmingham
    • Arizona
      • Scottsdale、Arizona、美国、85258
        • Pinnacle Oncology Hematology
    • California
      • Santa Monica、California、美国、90404
        • UCLA Hematology and Oncology
    • Indiana
      • Indianapolis、Indiana、美国、46202
        • Indiana University Simon Cancer Center

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Histologically proven advanced or metastatic solid cancer
  2. Measurable disease, evaluable disease or elevation of a relevant soluble tumor marker (e.g., CEA, PSA, CA125)
  3. Age of 18 years or older
  4. ECOG performance status of 0 or 1
  5. Resolution of all acute AEs resulting from prior cancer therapies to NCI CTCAE Grade ≤ 1 or baseline (except alopecia)
  6. Adequate organ function
  7. Willing and able to consent for self to participate in study

Exclusion Criteria:

  1. Prior treatment with TRC105
  2. Serious dose-limiting toxicity related to prior bevacizumab
  3. Current treatment on another therapeutic clinical trial
  4. Receipt of an investigational agent within 28 days of starting study treatment
  5. Prior surgery (including open biopsy) within 28 days of starting the study treatment
  6. Prior radiation therapy or systemic therapy within 21 days of starting the study treatment
  7. Minor surgical procedures such as fine needle aspirations, Mediport placement or core biopsies within 7 days of study treatment
  8. 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)
  9. Symptomatic pericardial or pleural effusions
  10. Uncontrolled peritoneal effusions requiring paracentesis more frequently than every 2 weeks
  11. 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)
  12. Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, DVT, PTCA or CABG within the past 6 months
  13. Active bleeding or pathologic condition that carries a high risk of bleeding
  14. Thrombolytic or anticoagulant use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
  15. Cardiac dysrhythmias of NCI CTCAE Grade ≥ 2 within the last 28 days
  16. Known active viral or nonviral hepatitis
  17. Centrally located non-small cell lung cancer (regardless of histologic sub-type), or non-small cell lung cancer of squamous histology.
  18. History of hemorrhage or hemoptysis (>½ teaspoon bright red blood) within 6 months of starting study treatment
  19. Open wounds or unhealed fractures within 28 days of starting study treatment
  20. 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
  21. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
  22. Pregnancy or breastfeeding

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:不适用
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的: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.
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.
其他名称:
  • 阿瓦斯汀
  • CD105 嵌合抗体 (TRC105)

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Determine Maximum Tolerated Dose of TRC105 in Combination With Bevacizumab
大体时间: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).
1.5 years

次要结果测量

结果测量
措施说明
大体时间
TRC105 Pharmacokinetic Concentrations
大体时间:1.5 years
Plasma TRC105 concentrations will be measured at specified timepoints.
1.5 years
Immune Response to TRC105
大体时间:1.5 years
HAMA and HACA titers will be measured at specified time-points.
1.5 years
Objective Response According to RECIST 1.1
大体时间:1.5 years
The best response according to RECIST 1.1 for each patient with measurable disease and who received at least one dose of study drug will be listed by cohort and tumor type
1.5 years

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 研究主任:Charles P Theuer, MD、Tracon Pharmaceuticals Inc.

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2011年4月1日

初级完成 (实际的)

2012年9月1日

研究完成 (实际的)

2013年12月1日

研究注册日期

首次提交

2011年4月7日

首先提交符合 QC 标准的

2011年4月8日

首次发布 (估计)

2011年4月11日

研究记录更新

最后更新发布 (实际的)

2018年12月5日

上次提交的符合 QC 标准的更新

2018年11月7日

最后验证

2018年11月1日

更多信息

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

成人实体瘤的临床试验

TRC105 and Bevacizumab的临床试验

3
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