NGR016: Randomized Phase II Study Evaluating Two Doses of NGR-hTNF Administered Either as Single Agent or in Combination With Doxorubicin in Patients With Advanced Soft Tissue Sarcoma (STS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 69
- 试验地点
- 7
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The main objective of the trial is to document the preliminary antitumor activity of two doses of NGR-hTNF administered either alone or in combination with doxorubicin in locally advanced or metastatic soft-tissue sarcoma (STS) patients untreated or previously treated with one or more prior systemic regimen.
详细描述
Considering the safety/toxicity profile of NGR-hTNF characterized by mild-to-moderate constitutional symptoms when given either every three weeks or weekly both at low (0.8 µg/m^2) and high dose (45 µg/m^2); the reversibility of these adverse events generally occurring only during the infusion time; the absence of overlapping toxicities with chemotherapeutic agents; and the safety and preliminary antitumor activity observed in phase Ib trial with doxorubicin, seems justified to evaluate in a randomized 4-arm phase II trial the preliminary antitumor activity of two doses of NGR-hTNF (0.8 µg/m^2 and 45 µg/m^2) administered weekly either alone or in combination with a standard dose of doxorubicin (60 mg/m^2 every three weeks).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologically-proven, locally advanced, or metastatic STS (excluding extraosseus Ewing sarcoma)
- •Patients not amenable to surgery, radiotherapy, or combined-modality therapy with curative intent
- •Patients untreated or previously treated with one or more systemic regimen
- •ECOG Performance status 0-2 (Appendix A)
- •At least one untreated (not previously irradiated) target lesion that could be measured in one dimension, according to RECIST criteria
- •A life expectancy of 12 weeks or more
- •Adequate baseline bone marrow, hepatic and renal function, defined as follows:
- •Neutrophils > 1.5 x 109/L and platelets > 100 x 109/L
- •Bilirubin < 1.5 x ULN
- •AST and/or ALT < 2.5 x ULN in absence of liver metastasis or < 5 x ULN in presence of liver metastasis
- •Serum creatinine < 1.5 x ULN
- •Creatinine clearance (estimated according to Cockcroft-Gault formula) ≥ 50 ml/min
- •Patients may have had prior treatment providing the following conditions are met before treatment start:
- •Surgery and radiation therapy: wash-out period of 14 days
- •Systemic therapy: wash-out period of 21 days
- •Patients must give written informed consent
排除标准
- •Patients may not receive any other investigational agents while on study
- •Patients with myocardial infarction within the last six (6) months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
- •LVEF < 55% (only for patients candidate for doxorubicin treatment)
- •Uncontrolled hypertension
- •Prolonged QTc interval (congenital or acquired) > 450 ms
- •History or evidence upon physical examination of CNS disease unless adequately treated (e.g., primary brain tumor, any brain metastasis, seizure not controlled with standard medical therapy) or history of stroke
- •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 or contraindications 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: low-dose NGR-hTNF
0.8 mcg/m² of NGR-hTNF
干预措施: low-dose NGR-hTNF (Drug)
B: high-dose NGR-hTNF
45 mcg/m² of NGR-hTNF
干预措施: high-dose NGR-hTNF (Drug)
C: low-dose NGR-hTNF + doxorubicin
0.8 mcg/m² of NGR-hTNF + doxorubicin
干预措施: low-dose NGR-hTNF (Drug)
C: low-dose NGR-hTNF + doxorubicin
0.8 mcg/m² of NGR-hTNF + doxorubicin
干预措施: Doxorubicin (Drug)
D: high-dose NGR-hTNF + doxorubicin
45 mcg/m² of NGR-hTNF + doxorubicin
干预措施: high-dose NGR-hTNF (Drug)
D: high-dose NGR-hTNF + doxorubicin
45 mcg/m² of NGR-hTNF + doxorubicin
干预措施: Doxorubicin (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: every 6-12 weeks
Defined as the time from the date of randomization until disease progression, or death
次要结局
- Response rate(every 6-12 weeks)
- Duration of Disease Control(every 6-12 weeks)
- Safety and Toxicity according to NCI-CTCAE criteria (version 4.02)(during the study)
- Overall survival (OS)(every 6-12 weeks)
- Tumor response(every 6-12 weeks)