此页面是自动翻译的,不保证翻译的准确性。请参阅 英文版 对于源文本。

Safety of 24-Hour Infusion of ON 01910.Na in Patients With Advanced Cancer

2017年6月22日 更新者:Onconova Therapeutics, Inc.

Phase I Dose Escalation Study of ON 01910.Na by 24 Hour Continuous Infusion Per Week in Patients With Advanced Cancer

The primary purpose of this study is to determine the highest dose of ON 01910.Na that can be safely given as an intravenous infusion over 24 hours once a week in a 3-week cycle to patients with advanced solid tumors.

研究概览

地位

完全的

详细说明

This is an open-label, dose-escalating Phase I study of ON 01910.Na in patients with advanced cancers, who have satisfied the inclusion/exclusion criteria enumerated in this protocol. Patients will receive ON 01910.Na intravenously by 24 hour continuous infusion once every week (3 weeks per cycle), until evidence of disease progression, intolerable adverse events, or withdrawal of patient consent. Safety monitoring will be done for at least 3 weeks before escalation to the next dose level. As of Amendment 7, up to 6 patients with gynecological malignancies will be enrolled at the 2400 mg/m2 dose level to determine the appropriateness of this dose as the Recommended Phase Two Dose (RPTD).

研究类型

介入性

注册 (实际的)

42

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

    • New York
      • The Bronx、New York、美国、10461
        • Albert Einstein 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

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Must have histologically confirmed solid tumor (leukemias and lymphomas excluded) malignancy that is incurable and for which standard (FDA approved or established standard clinical practice), curative, or palliative measures do not exist or are no longer effective.
  • Patients with disease amenable to sequential biopsies will be requested to undergo two tumor biopsies and two normal skin biopsies, but patients may decline and still be eligible for enrollment during this escalation stage.
  • At least 3 weeks since the last dose of other potentially myelosuppressive treatment (at least 6 weeks since last dose of nitrosoureas or mitomycin C) and recovery from manifestations of reversible drug toxicity (alopecia, stable residual neuropathy, and residual hand and foot syndrome are excluded). Patients with prior doxorubicin chemotherapy must have total cumulative dose of no more than 450 mg/m2.
  • Patients with prior radiotherapy are eligible provided a minimum of 4 weeks have passed and the maximal area of hematopoietic active bone marrow treated was less than 25%.
  • ECOG performance status ≤2.
  • Patients must have nearly normal organ and marrow function as defined below:
  • Hgb > 9 gm/dl (must not require transfusional support but erythropoietin therapy is permitted)
  • WBC > 4,000 per microliter
  • Absolute neutrophil count > 1,500 per microliter
  • Platelets ≥ 100,000 per microliter
  • Total bilirubin within 1.5 times institutional upper normal limit
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper normal limit. (If liver function abnormalities are due to metastatic disease, patients are eligible provided the transaminases are < 5 times institutional upper normal limit. Patients with primary liver disease with these parameters will be ineligible.)
  • Serum creatinine within normal institutional limits or estimated creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
  • Women of child-bearing potential and men must agree to use adequate contraception prior to study entry.
  • Ability to understand and the willingness to sign a written informed consent document.
  • All ethnic groups are eligible for this trial.

Inclusion Criteria - Dose Confirmation Phase Same inclusion criteria as in the Dose Escalation phase described above, except Patients must have an ECOG performance of 0 or 1.

Exclusion Criteria:

  • Recent major surgery (within the past 14 days), chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 4 weeks prior to entering the study, or those who have not recovered from adverse events (except alopecia, stable residual neuropathy, and residual hand and foot syndrome) due to previously administered agents.
  • Patients may not be on any other investigational agents or concurrent chemotherapy, radiotherapy, hormonal treatments, bone marrow transplantation, or immunotherapy. Patients who have previously had a Bone Marrow Transplant are excluded from this study.
  • Known brain metastases, except brain metastases that have been previously removed or irradiated and currently have no clinical impact.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ON 01910.Na.
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, bleeding, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant and nursing women are excluded.
  • HIV-positive patients receiving combination anti-retroviral therapy are excluded.
  • Ascites requiring active medical management including paracentesis, peripheral bilateral edema, hyponatremia (serum sodium value less than 134 Meq/L).

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)

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
Number of dose limiting toxicities (DLTs)
大体时间:21 days after first administration of ON 01910.Na

DLTs are defined as:

  • Grade 3 non-hematological toxicity other than nausea, vomiting, diarrhea, fever, stomatitis, esophagitis/dysphagia.
  • Recurrent grade 3 toxicity uncontrolled by optimal therapy or Grade 4 nausea, vomiting, diarrhea and fever.
  • Grade 3 stomatitis and/or esophagitis/dysphagia for > 5 days.
  • Grade 4 neutropenia or thrombocytopenia for > 5 days measured at least 2X 2-3 days apart.
  • Neutropenic fever, as defined in Protocol.
  • Failure to recover neutrophils (> 1,500 per microliter) or platelets (>75,000 per microliter) before the next weekly dose.
21 days after first administration of ON 01910.Na

次要结果测量

结果测量
措施说明
大体时间
Number of Adverse Events (AEs)
大体时间:30 days after last infusion of study drug
All AEs (except Grade 1 and 2 laboratories abnormalities that do not require an intervention) are recorded in Case Report Forms and source documentation.
30 days after last infusion of study drug
Severity of Adverse Events (AEs)
大体时间:30 days after last infusion of study drug
Severity of AEs are determined according to Common Terminology Criteria for Adverse Events (Version 3.0)
30 days after last infusion of study drug
不良事件 (AE) 与研究治疗药物的关系
大体时间:最后一次输注研究药物后 30 天
根据协议附录 II 中的指导,关系被评估为不相关、不太可能、可能、可能或肯定。
最后一次输注研究药物后 30 天
Concentration of ON 01910.Na in plasma versus time
大体时间:Up to 48 hours after infusion of study drug during Week 1 in Cycles 1 and 2
Blood samples will be collected at following time points: Pre-dose; 1 h after start of infusion; 3 h; 6 h; 12 h; 18 h; 24 h; 10 min after end of infusion; 20 min; 30 min; 1 h; 2 h; 4 h; 8 h; 24 h; and, 48 h. Plasma will be prepared from these samples. Concentration of ON 01910.Na will be determined by validated method.
Up to 48 hours after infusion of study drug during Week 1 in Cycles 1 and 2
基线时记录的目标病灶大小的变化
大体时间:最后一次输注研究药物后 30 天
在基线和每次随访时,将对每个已识别和记录的病变使用相同的评估方法。
最后一次输注研究药物后 30 天

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

  • 首席研究员:Sridhar Mani, MD、Albert Einstein College of Medicine

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

  • Garcia-Manero G, Fenaux P. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Blood Dec 2016, 128 (22) 2011; ASH 2016.

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

2006年6月1日

初级完成 (实际的)

2010年7月1日

研究完成 (实际的)

2011年11月1日

研究注册日期

首次提交

2012年2月20日

首先提交符合 QC 标准的

2012年2月23日

首次发布 (估计)

2012年2月24日

研究记录更新

最后更新发布 (实际的)

2017年6月23日

上次提交的符合 QC 标准的更新

2017年6月22日

最后验证

2017年6月1日

更多信息

与本研究相关的术语

其他研究编号

  • Onconova 04-03

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.

订阅