A Phase 1, Open-Label, Dose Escalation Study of ANG1005 in Patients With Advanced Solid Tumors and Metastatic Brain Cancer
研究概览
详细说明
This is a phase 1, multi-centre, sequential cohort, open-label, dose-escalation study of the safety, tolerability, and PK of ANG1005 in patients with solid tumors (with or without brain metastases). ANG1005 will be given by IV infusion once every 21 days (1 treatment cycle). Each patient will participate in only 1 dose group and will receive up to 6 cycles. Patients may receive additional cycles of ANG1005 if there is no evidence of tumor progression, there is recovery to ≤Grade 1 or baseline nonhematologic, ANG1005-related toxicity (except alopecia), the absolute neutrophil count is ≥1.5 x 109/L, and the platelet count is ≥100 x 109/L.
Initially, cohorts of 1 - 3 patients will be enrolled into each dose group. Dose escalation by dose doubling will be done for the first 3 dose groups followed by a modified Fibonacci dose escalation scheme with increases of 67%, 50%, 40% and 33% thereafter. If 1 or more patients in a cohort experience an emergent ≥ Grade 2 drug-related toxicity during the first treatment cycle, then a minimum of 3 patients will be enrolled into that, and all subsequent cohort(s) and dose doubling will be stopped if applicable.
If > 1 patient in a cohort experience a dose limiting toxicity (DLT) during the first treatment cycle, defined as any of the following that are both treatment-emergent and at least possibly related to ANG1005: i) Any Grade 3 or 4 nonhematologic toxicity, ii) Febrile neutropenia, iii) Grade 4 neutropenia of ≥7 days duration, and/or iv) Any Grade 4 thrombocytopenia, then dose escalation will stop and prior doses will be explored as the maximum tolerated dose (MTD), that dose-level at which ≤1 of 6 patients in a cohort develop an emergent DLT).
Once the MTD is established, approximately 14 patients will be enrolled at that dose-level in order to further assess the safety and tolerability of ANG1005, the PK profile of ANG1005 at the MTD, and the preliminary anti-tumor activity of ANG1005 in patients with solid tumors (with or without brain metastases).
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
-
-
Ohio
-
Canton、Ohio、美国、44718
- Gabrail Cancer Center
-
-
Texas
-
Houston、Texas、美国、77030
- University of Texas, MD Anderson Cancer Center
-
San Antonio、Texas、美国、78229
- UT Health Science Center, Cancer Therapy and Research Center
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Written informed consent
- Histologically or cytologically confirmed metastatic or advance-stage solid tumor that has progressed following standard therapy or for which, in the opinion of the Investigator, no standard effective therapy is available; patients without brain metastases may be enrolled into the dose-escalation part of the study
- Patients enrolled into the expanded MTD cohort must have shown unequivocal evidence of brain metastases
- Male and female patients.
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- An expected survival of at least 3 months
- Measurable disease according to RECIST criteria; patients with brain metastases must have at least one measurable lesion in the brain, according to RECIST criteria
- Male and female subjects who are not surgically sterile or post-menopausal must agree to use reliable methods of birth control for the duration of the study and for 90 days after the last dose of study drug administration; male partners of female subjects should use condoms for the duration of the study, and for 90 days after the last dose of study drug administration
Exclusion Criteria:
- Chemotherapy, radiotherapy (except palliative radiation delivered to <20% of bone marrow), or investigational agents within 4 weeks before the first dose of study drug. Biologic therapy (such as 13-cis-retinoic acid, thalidomide, tamoxifen, celebrex, erlotinib, imatinib, vorinostat, and lapatinib) and immunotherapy (such as interferon a or b, cdx-110 (EGFR vIII vaccine), interleukin 2, thalidomide) within 1 week before the first dose of study drug. Bevacizumab within 6 weeks before the first dose of study drug
- Pregnant or lactating females
- Any acute viral, bacterial, or fungal infection that requires parenteral therapy within 14 days prior to study treatment
- Known severe hypersensitivity to paclitaxel
- Severe toxicity with previous taxane treatment
- Treatment with P450 CYP 3A4 or CYP 2C8 enzyme-inducing anti-convulsant drugs within 14 days prior to treatment with study drug
- Patients with inadequate hematological, liver, and renal function
- Known or suspected acute or chronic active Hepatitis B, Hepatitis C, or HIV/AIDS
- Patients with unstable or uncompensated respiratory, cardiac, hepatic or renal disease or any other organ system dysfunction, medical condition, or laboratory abnormality which, in the opinion of the Investigator, would either comprise the patient's safety or interfere with the evaluation of the test material
- Evidence of persistent Grade 2 or greater neurotoxicity
学习计划
研究是如何设计的?
设计细节
- 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:1个
|
每 21 天静脉滴注一次
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
To characterize the safety and tolerability of intravenously administered ANG1005 in patients with advanced solid tumors and metastatic brain cancer.
大体时间:On-going
|
On-going
|
To identify the maximum tolerated dose (MTD) of ANG1005 in patients with advanced solid tumors and metastatic brain cancer.
大体时间:End of dose escalation
|
End of dose escalation
|
次要结果测量
结果测量 |
大体时间 |
---|---|
检查 ANG1005 的药代动力学 (PK)。
大体时间:研究结束
|
研究结束
|
确认 ANG1005 在 MTD 下的安全性和耐受性。
大体时间:剂量递增结束
|
剂量递增结束
|
评估 ANG1005 的免疫原性。
大体时间:研究结束
|
研究结束
|
To obtain preliminary information on the antitumor activity of ANG1005 in patients with advanced solid tumors with brain metastases.
大体时间:On-going
|
On-going
|
合作者和调查者
出版物和有用的链接
有用的网址
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
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.
ANG1005的临床试验
-
Angiochem Inc终止
-
Angiochem Inc完全的