Phase I Study of tTF-NGR in Patients With Recurrent or Refractory Malignant Tumors and Lymphomas Beyond All Standard Treatments
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD) and Dose-limiting Toxicity (DLT)
研究概览
简要总结
In this phase I clinical trial cancer patients suffering from solid tumors or lymphomas, recurring after and/or refractory against standard treatment are treated intravenously (iv) with increasing doses of tTF-NGR(tTF= truncated tissue factor; NGR=Asn-Gly-Arg). The objectives of this trial are to evaluate the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of intravenously (iv) infused daily applications of tTF-NGR for 5 days every 3 weeks in patients with cancer, who had obtained all standard treatment known for their disease entity prior to entry on study. Further objectives are to determine the perfusion and vascular volume fraction of measurable tumor lesions versus normal reference tissue before and after tTF-NGR application by MRI as a biological surrogate parameter for biological activity of the investigational medicinal product (IMP), tTF-NGR, and to obtain pharmacokinetic data.
详细描述
PHASE I STUDY OF tTF-NGR IN PATIENTS WITH RECURRENT OR REFRACTORY MALIGNANT TUMORS OR LYMPHOMAS BEYOND ALL STANDARD TREATMENTS
Short Title: tTF-NGR Phase I Study Sponsor's Study Code: UKM12_0018
EudraCT-No.: 2016-003042-85 Sponsor: Universitätsklinikum Muenster Investigator: Prof. Dr. Christoph Schliemann
Indication: All solid tumors and lymphomas beyond standard therapy Study Design: Phase I Study Investigational Medicinal Product: tTF-NGR
Therapy: Phase I, open label, single arm, non-randomized prospective, monocenter study. tTF-NGR will be given as 1-hour infusion via central venous access once daily for 5 days with a subsequent rest period of 2 weeks and following cycles with dose escalation of 0.5 mg/m2 upon judgement of tolerability and therapeutic activity. Starting dose will be 1 mg/m2/day. Patients within the dose-escalation part will be treated in sequence and not in parallel. Individual patients can undergo a maximum of 8 dose-escalations. Dose-escalation is stopped before the maximum number of 8 escalation steps if tumor response, tumor progression or a Dose-Limiting Toxicity (DLT) is observed. In the case of stable disease (SD) and with good tolerability these patients can obtain further cycles without dose-escalation until tumor progression or Dose-Limiting Toxicity (DLT) and the next patient can start with dose-escalation cycles on the highest tolerable dose for the previous patient.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •age ≥ 18 years
- •histologically proven or cytologically confirmed solid malignant tumor or malignant lymphoma
- •recurrent or refractory disease after standard therapy and with no known curative or survival-prolonging treatment options according to the judgement of the investigators
- •life expectancy of at least 6 weeks according to the judgement of the investigators
- •Karnofsky performance status ≥ 50
- •measurable disease with at least one marker-lesion measurable in 2 dimensions by Vascular Volume-Fraction-MRI and/or CEUS.
- •adequate bone marrow function with absolute neutrophil count > 1000/microliter and platelet count > 50/nl
- •normal global coagulation parameters (Quick, partial thromboplastin time (PTT), thrombin time (TZ), fibrinogen), no prophylactic anticoagulation
- •ability to understand and provide written informed consent
- •adequate liver function (total bilirubin < 3x the upper normal limit (ULN), serum glutamic pyruvic transaminase/serum glutamic-oxaloacetic transaminase (SGPT/SGOT) < 3x ULN)
- •adequate renal function (serum creatinine < 3x ULN)
- •no history of coronary heart disease, stroke, transitory ischemic attacks, pulmonary embolism, or deep vein thrombosis
- •time elapsed from previous therapy (including other IMPs) ≥ 3 weeks with recovery from side effects
- •exclusion of central nervous system (CNS) disease and CNS vascular abnormalities by MRI
- •ability to understand and provide written informed consent
- •written informed consent given
- •for female patients with child-bearing potential exclusion of pregnancy by adequate testing within 48 hours prior to entry on study
- •females of childbearing potential as well as fertile males must agree to use a highly effective form of contraception (Pearl Index < 1) during the study and for 120 days following the last dose of the IMP
排除标准
- •clinically significant unrelated illness which in the judgement of the investigators could compromise the patient's ability to tolerate the IMP or be likely to interfere with the study procedures or results
- •known hypersensitivity reactions to prior application of E. coli-derived material
- •women with breast-feeding activity
- •concomitant use of any other investigational agent (agent for which there is currently no approved indication from regulatory authorities)
- •clinical application of any other drug with known anti tumor activity
- •prophylactic anticoagulation within the last 3 days
- •NOTE: Since this is a phase I study for end-stage cancer patients, patients who would be excluded from the protocol strictly for laboratory abnormalities only can be included at the Investigator's discretion. This will be documented as an exception to the criteria and will be signed and filed in the CRF and the Trial Master File.
结局指标
主要结局
Maximum Tolerated Dose (MTD) and Dose-limiting Toxicity (DLT)
时间窗: Measures: daily during treatment, weekly during rest periods of 2 weeks, monthly after End of Therapy, up to 3 months.
DLT will be characterized by clinical, blood and serum monitoring at specified time points before and during study period. AE, SAE, and SUSAR reporting was according to CTCAE 4.0 and GCP guidelines.
次要结局
- 1: Assessment of Anti-tumor Activity: MRI K-trans in [ 10^-3/Min] and/or CEUS in [Arbitrary Units]; 2: Pharmacokinetic Profile: AUC in [ng*h/mL](1: Tumor blood flow: baseline, 5 h post-dose, at 5 d at each cycle of therapy and 6 months. 2: Pharmacokinetic measures: 0 h, 0.5 h, 1 h, 1.5 h, 3 h, 2.5 h, 3 h, 3.5 h, 4 h, 4.5 h, 5 h post-dose)