A Phase IB Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 4
- 主要终点
- Number of Adverse Events From Escalating Doses of NGR-hTNF in Combination With a Fixed Dose of Doxorubicin
研究概览
简要总结
The main objective of the trial is to document the safety of the combination (escalation doses of NGR-hTNF, from 0.2 mcg/sqm to 1.6 mcg/sqm , with a fixed dose of doxorubicin, 75 mg/sqm). Safety will be established by clinical and laboratory assessment according to National Cancer Institute Common Toxicity Criteria (NCI-CTC ).
详细描述
This is a phase IB, open-label, non-randomized, dose-escalation study that will be conducted in sequential cohorts of patients. Three patients per each cohort are planned.
Patients, with advanced or metastatic solid tumor previously treated with a non cumulative dose of doxorubicin (<300 mg/sqm in order to allow an adequate number of cycles) or chemotherapy naïve will be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Patients ≥18 years old with proven advanced or metastatic solid tumor not amenable to any clinical improvement by current standard treatments and previously treated with a non cumulative dose of anthracyclines (<300 mg/sqm) or chemotherapy naïve.
- •Life expectancy more than 3 months.
- •ECOG performance status 0 -
- •Normal cardiac function (left ventricular ejection fraction [LVEF] ≥55%) and absence of uncontrolled hypertension.
- •Absence of any conditions involving hypervolemia and its consequences.
- •Adequate baseline bone marrow, hepatic and renal function, defined as follows:
- •Neutrophils > 1.5 x 10^9/L and platelets >100 x 10^9/L Bilirubin < 1.5 x ULN AST and/or ALT < 2 x ULN Serum creatinine < 1.5 x ULN
- •Patients may have had prior therapy providing the following conditions are met:
- •Chemo, radio, hormonal, immuno or anti-vascular therapy: wash-out period of 28 days.
- •Surgery: wash-out period of 14 days.
- •Patients must give written informed consent to participate in the study.
排除标准
- •Concurrent anticancer therapy
- •Patients must not receive any other investigational agents while on study
- •Patients with a LVEF <55%
- •New York Heart Association class III or IV cardiac disease
- •Acute angina
- •Patients with myocardial infarction within the last six (6) months
- •Patient with significant peripheral vascular disease
- •Thrombosis of main portal vein
- •Previous signs of severe toxicity doxorubicin related
- •Previous signs of cardiotoxicity doxorubicin related
- •Patients previously treated with a cumulative dosage of anthracyclines ≥300 mg/m^2
- •Clinical signs of CNS involvement
- •Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
- •Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
- •Pregnancy or lactation. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of child-bearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration
研究组 & 干预措施
A
干预措施: NGR-hTNF (Drug)
A
干预措施: Doxorubicin (Drug)
结局指标
主要结局
Number of Adverse Events From Escalating Doses of NGR-hTNF in Combination With a Fixed Dose of Doxorubicin
时间窗: Through study completion, an average of 1 year
An Adverse Event (AE) is any untoward medical occurrence or experience in a patient or clinical investigation subject treated administered a pharmaceutical product and which does not necessarily have to have a casual relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
次要结局
- Pharmacokinetic Profiles of NGR-hTNF Administrated in Combination With Doxorubicin (Tmax)(prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes)
- Pharmacokinetic Profiles of NGR-hTNF Administrated in Combination With Doxorubicin (AUC0-t(Last))(prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes)
- Pharmacokinetic Profiles of NGR-hTNF Administrated in Combination With Doxorubicin (Cmax)(prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes)
- sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (Eav)(prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes)
- sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (Emax)(prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes)
- To Evaluate Phenotype Analysis and Adaptative Immune Response(during the study)
- Signs of Anticancer Activity by Standard Imaging or Clinically; When Possible Tumor Response Will be Documented According to RECIST Criteria(after the first 2 cycles(Follow-up 2) of treatment and then every 2 cycles (Follow-up 4,6..). In case of detection of a complete or partial response, a confirmation assessment must be performed ≥ 4 weeks after the first documentation of the response.)
- sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (Tmax)(prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes)
- sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (ARC)(prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes)