NCT02808247终止2 期
A Phase II Multicenter Study Comparing the Efficacy of the Oral Angiogenesis Inhibitor Nintedanib With the Intravenous Cytotoxic Compound Ifosfamide for Treatment of Patients With Advanced Metastatic Soft Tissue Sarcoma After Failure of Systemic Non-oxazaphosporine-based First Line Chemotherapy for Inoperable Disease "ANITA"
European Organisation for Research and Treatment of Cancer - EORTC13 个研究点 分布在 7 个国家目标入组 80 人开始时间: 2017年7月7日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 80
- 试验地点
- 13
- 主要终点
- progression-free survival (PFS)
研究概览
简要总结
This is a prospective, multicentric, randomized, open label Phase II trial investigating whether the oral angiogenesis inhibitor nintedanib, as compared to the intravenous cytotoxic compound ifosfamide, given for patients with advanced, inoperable and/or metastatic STS after failure of first line chemotherapy prolongs progression-free survival.
The primary objective of the trial is to evaluate whether nintedanib given as second-line therapy for advanced, inoperable and/or metastatic STS prolongs progression-free survival when compared with ifosfamide.
Secondary objectives are to evaluate the efficacy of nintedanib as compared to ifosfamide in terms of progression-free survival rate at 12 weeks, overall survival, objective response rate, patient benefit rate, response duration, total duration of treatment with nintedanib safety, Health related Quality of Life and Health Economics.
Exploratory objectives include an analysis of putative predictive biomarkers for the anti-tumor effects of the investigational agent nintedanib.treatment.
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
- 未提供
排除标准
- •Histologically proven advanced, inoperable and/or metastatic malignant STS of intermediate or high grade, excluding the:
- •Well-differentiated liposarcoma/atypical lipoma
- •Embryonal rhabdomyosarcoma
- •Chondrosarcoma (extraskeletal myxoid chondrosarcoma is eligible)
- •Osteosarcoma (extraskeletal osteosarcoma is eligible)
- •Ewing family of tumors/primitive neuroectodermal tumor
- •Gastro-intestinal stromal tumor
- •Dermatofibrosarcoma protuberans
- •For STS where no established grading system exists, or sarcoma subtypes which are very indolent or have an unpredictable clinical behavior, patient entry requires prospective approval in writing, on a case-by-case basis by the Study Coordinator of this trial and EORTC Headquarters (HQ).
- •Representative formalin fixed, paraffin embedded tumor blocks or unstained tissue slides, either from the primary tumor or a metastatic lesion, must be available for histological central review. Histological central review is not required before treatment start but it is mandatory to send unstained tumor slides (blocks optional) at time of study entry. Local histopathological diagnosis will be accepted for entry into this trial.
- •Prior to study enrolment, all patients need to have confirmed RECIST 1.1 disease progression based on local investigator's assessment.
- •Presence of measurable disease according to RECIST 1.
- •Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered non-measurable unless there has been demonstrated progression (20 % increase) in the assessed lesion since the local treatment.
- •No radiographic evidence of cavitary lesions (either primary tumor or metastatic lesions).
- •No centrally located tumors with radiographic evidence of local invasion of major blood vessels.
- •No history of central nervous system metastasis or leptomeningeal tumor spread.
- •No active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomization).
- •One (and no less or more than one) line of previous systemic chemotherapy for advanced, inoperable and/or metastatic malignant STS.
- •Prior neoadjuvant, adjuvant and or first-line maintenance systemic chemotherapy for locally advanced or metastatic STS is allowed and does count as zero lines of treatment, provided that the disease did not progress during neoadjuvant and/or adjuvant therapy or within 12 weeks after completion of the perioperative treatment. In case the disease progressed during neoadjuvant, adjuvant and or first-line maintenance systemic chemotherapy or within 12 weeks after its completion, the treatment is counted as one line and the patient can theoretically participate in the trial, provided all other selection criteria are met.
- •No prior exposure to an oxazaphosphorine agent, including but not limited to ifosfamide, cyclophosphamide, trofosfamide or evofosfamide (TH-302).
- •No prior exposure to oral or intravenous angiogenesis inhibitors, including but not limited to tyrosine kinase inhibitors such as pazopanib, sunitinib, sorafenib, axitinib or similar or monoclonal antibodies targeting angiogenesis.
- •No other anti-cancer therapy (systemic therapy, radiotherapy (except for brain and extremities), surgery, limb perfusion, immunotherapy) within 28 days prior to randomization.
- •No treatment with another investigational agent within 28 days prior to randomization.
- •No treatment with another investigational agent concomitantly with the trial.
- •No known hypersensitivity to or known specific contraindications for the use of nintedanib or ifosfamide.
- •No known hypersensitivity to peanut or soy bean.
- •Age 18 years or older.
- •WHO performance status (PS) 0-
- •Life expectancy of at least 3 months.
- •Adequate bone marrow, liver and renal function and coagulation parameters:
- •neutrophils ≥ 1.5 x 109/L;
- •hemoglobin ≥ 9 g/dL (or ≥ 5.6 mmol/L). Blood transfusions or the administration of hematopoietic growth factors are allowed to achieve these baseline values;
- •platelets ≥ 100 x 109/L. Platelet transfusions or the administration of hematopoietic growth factors are allowed to achieve these baseline values;
- •Total bilirubin ≤ ULN;
- •Patients with Gilbert syndrome and/or bilirubin < 2xULN and normal AST/ALT are eligible;
- •SGPT/ALT and SGOT/AST ≤ 2.5 x ULN for patients with liver metastasis;
- •SGPT/ALT and SGOT/ AST ≤ 1.5x ULN for patients without liver metastasis;
- •Serum creatinine or creatinine clearance/eGFR within normal limits to baseline, assessed as per local standard method;
- •No proteinuria CTCAE grade 2 or greater;
- •International normalized ratio (INR) ≤ 2;
- •Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 50% of institutional ULN.
- •No Child Pugh B or C hepatic impairment.
- •Normal cardiac function (left ventricular ejection fraction (LVEF) assessed by multi-gated acquisition scan or cardiac ultrasound within normal range of the institution), 12 lead electrocardiogram (ECG) without clinically relevant abnormalities. No Class III or IV congestive heart failure, angina pectoris, myocardial infarction within 1 year before registration/randomization, clinically significant cardiac arrhythmia or pericardial effusion.
- •No uncontrolled arterial hypertension defined at baseline as blood pressure ≥ 150/100 mmHg despite adequate medical therapy.
- •No use of therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325 mg per day).
- •No known inherited predisposition for bleeding or thromboembolism.
- •No history of clinically significant hemorrhagic or thromboembolic event in the past 6 months.
- •Absence of active or uncontrolled infections in particular if requiring systemic antibiotics or antimicrobial therapy.
- •No previous encephalopathy of any cause or other significant neurological condition.
- •No acute or chronic, clinically relevant inflammation of urinary bladder.
- 另有 13 项未显示
研究组 & 干预措施
Experimental arm (arm A): Nintedanib
Experimental
Nintedanib 200 mg twice daily orally. Nintedanib will be given continuously until clinically relevant disease progression according to the investigator's assessment or until other criteria for treatment discontinuation are met as specified in the protocol. Dosing beyond RECIST 1.1 progression is allowed for the oral agent if the patient still derives benefit from the treatment.
干预措施: Nintedanib (Drug)
Standard arm (arm B): Ifosfamide
Active Comparator
Ifosfamide 3 g/m2 intravenously on days 1, 2 and 3 every 21 days for up to a maximum of 6 cycles.
干预措施: Ifosfamide (Drug)
结局指标
主要结局
progression-free survival (PFS)
时间窗: 4 years from first patient in
progression-free survival (PFS) defined according to RECIST 1.1.
次要结局
- Progression-free survival rate at 12 weeks (binary)(4 years from first patient in)
- Objective response rate(4 years from first patient in)
- Health economics (EQ-5D-5L, health care resource utilities)(4 years from first patient in)
- Overall survival(4 years from first patient in)
- Response duration(4 years from first patient in)
- Clinical benefit rate(4 years from first patient in)
- Total duration of treatment with nintedanib (including treatment beyond RECIST progression)(4 years from first patient in)
- Safety (Common Toxicity Criteria CTCAE 4.0)(4 years from first patient in)
- Health related quality of life (QLQ-C30)(4 years from first patient in)
研究者
研究点 (13)
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