Cilengitide and Metronomic Temozolomide for Relapsed or Refractory High Grade Gliomas or Diffuse Intrinsic Pontine Gliomas in Children and Adolescents - A Phase II Study HIT-HGG-CilMetro - A Clinical Phase II Trial of the HIT-HGG Study Group -
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Efficacy of a combined treatment with cilengitide and temozolomide as measured by 6 months overall survival after diagnosis of relapsed or refractory high grade glioma or diffuse intrinsic pontine glioma in children and adolescents
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of a combined treatment with cilengitide and metronomic oral temozolomide as measured by 6 months overall survival (OS) after diagnosis of relapse or tumour progression in children and adolescents with relapsed or refractory high-grade malignant glioma and diffuse intrinsic pontine glioma.
Secondary objectives include:
- To evaluate the safety and toxicity of the study treatment by common toxicity criteria (CTC; version 4.0).
- To assess
- the response rates at 6 months (continuous complete response = CCR, complete response = CR, partial response = PR, stable disease = SD, progressive disease = PD) and
- progression-free survival (PFS) at 6 months, and
- response rates, OS, and PFS at 12 months after relapse diagnosis or diagnosis of tumor progression. Response will be presented including histopathological variants.
- To assess the pharmacokinetics of cilengitide administered as part of the study treatment.
Indication and study population for this trial:
Treatment of relapsed or refractory high grade gliomas and diffuse intrinsic pontine gliomas in paediatric patients ≥ 3 years and < 18 years of age.
Patients included in the study receive
- Cilengitide 1800 mg/m² i.v. twice weekly
- Temozolomide 75 mg/m²/d p.o. for 6 weeks, followed by 1 week rest with a mandatory platelet-count dependent dose adaptation rule: mandatory blood counts twice weekely: Platelets ≥ 100 000/µl (≥ 100 Gpt/l): 75 mg/m², platelets ≥ 50 000 - < 100 000/µl (≥ 50 - <100 Gpt/l): 50 mg/m², platelets < 50 000/µl (<50 Gpt/l): stop temozolomide until platelet recovery ≥ 100 000/µl (≥100 Gpt/l)
- Study treatment in the individual patient is scheduled for 1 year unless tumor progression or excessive toxicity occurs. However, study treatment may be extended beyond 1 year upon individual decision.
详细描述
Indication:
Treatment of relapsed or refractory high grade gliomas and diffuse intrinsic pontine gliomas in paediatric patients ≥ 3 years and < 18 years of age.
Background and rationale:
Relapsed or refractory high-grade gliomas or diffuse intrinsic pontine gliomas (in the following both addressed as high grade gliomas = HGG) in children and adolescents represent a very bad prognosis group for which a recommended standard salvage therapy is currently not available.
The combination of cilengitide and metronomic temozolomide will be investigated in the present trial as new treatment strategy for these patients.
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
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of high-grade malignant glioma confirmed by central neuropathological review (last MRI diagnosis not older than 4 weeks) - including glioblastoma multiforme (WHO IV), anaplastic astrocytoma (WHO III), anaplastic oligodendroglioma (WHO III), anaplastic oligoastrocytoma (WHO III), anaplastic pilocytic astrocytoma (WHO III), anaplastic ganglioglioma (WHO III), anaplastic pleomorphic xanthoastrocytoma (analogous to WHO III), giant cell glioblastoma (WHO IV), and gliosarcoma (WHO IV) - or diagnosis of diffuse intrinsic pontine glioma confirmed by central neuroradiological review - refractory to standard treatment, or relapsed or progressive after first-line therapy.
- •Patient aged 3 years and older but under 18 years at time of relapse diagnosis
- •Written informed consent of the patient (mandatory from 15 years of age) or the parents (mandatory till 18 years of age).
排除标准
- •Known hypersensitivity or contraindication to any study drugs
- •Other (simultaneous) malignancies
- •Pregnancy and / or lactation
- •Patients who are sexually active refusing to use effective contraception (oral contraception, intrauterine devices, barrier method of contraception in conjunction with spermicidal jelly or surgical sterile)
- •Current or recent (within 30 days prior to start of trial treatment) treatment with another investigational drug or participation in another investigational trial
- •Severe concomitant diseases (e.g. immune deficiency syndrome) or HIV infection
- •Severe psychological disease or neurological damage without possibility to communicate
- •Clinical signs of intracranial pressure
- •Intracerebral hemorrhage or history of intracerebral hemorrhage
- •Requirements for laboratory test results not older than 2 weeks before patient´s inclusion:
- •Platelets < 100 000/µl (< 100 Gpt/l) PT, INR and PTT above normal range Absulute neutrophil count ≤ 1 500/µl (< 1,5 Gpt/l) Hemoglobin < 10g/dl (< 6,4 mmol/L) Serum creatinine ≥ 1,5 x upper limit of normal range or creatinine clearance rate ≤ 60 ml/min/m2 (corrected for body surface area) Total bilirubin ≥ 1,5 x upper limit of normal range SGOT (ASAT) and SGPT (ALAT) ≥ 2,5 x upper limit of normal range Alkaline phosphatase ≥ 2,5 x upper limit of normal range
- •Hereditary Intrinsic Platelet Disorders
- •Ongoing irradiation or chemotherapy (within the last 4 weeks)
- •Estimated life expectancy of less than 2 months
研究组 & 干预措施
Cilengitide and metronomic temozolomide
Cilengitide 1800 mg/m² i.v. twice weekly and Temozolomide 75 mg/m²/d p.o. for 6 weeks, followed by 1 week rest with a mandatory platelet-count dependent dose adaptation rule
干预措施: Cilengitide (Drug)
Cilengitide and metronomic temozolomide
Cilengitide 1800 mg/m² i.v. twice weekly and Temozolomide 75 mg/m²/d p.o. for 6 weeks, followed by 1 week rest with a mandatory platelet-count dependent dose adaptation rule
干预措施: Temozolomide (Drug)
结局指标
主要结局
Efficacy of a combined treatment with cilengitide and temozolomide as measured by 6 months overall survival after diagnosis of relapsed or refractory high grade glioma or diffuse intrinsic pontine glioma in children and adolescents
时间窗: 6 months
Evaluation of overall survival after 6 months
次要结局
- Response rates (RR) at 6 months, progression-free survival (PFS) at 6 months, and RR, overall survival (OS), and PFS at 12 months after relapse diagnosis or diagnosis of tumor progression(Response rates and progression-free survival at 6 and 12 months, overall survival at 12 months (Trial subjects will be followed up for at least 1 year and 30 days after study entry))
- Safety and toxicity of the study treatment(Up to 52 weeks of treatment and subsequently 30 days after end of treatment)
- Peak plasma levels of cilengitide [ng/ml] on day 1 of week 1 and day 4 of week 6(Day 1 of treatment week 1: Immediately before and immediately after as well as 2, 4, and 7 hours after end of cilengitide administration; day 4 of treatment week 6: 2 hours after end of cilengitide adminstration)
研究者
Christof Kramm
Principal investigator (
Martin-Luther-Universität Halle-Wittenberg