A Phase 1 Study of Intravenous EGFR-ErbituxEDVsMIT (EEDVsMit) in Children With Recurrent / Refractory Solid or CNS Tumours Expressing Epidermal Growth Factor Receptor (EGFR) (ECREST Study)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- MTD at which fewer than one third of patients experience dose limiting toxicity as assessed by CTCAE v4.0
研究概览
简要总结
This is an open-label, sequential dose exploration study of single agent EEDVSMit administered by intravenous (IV) infusion twice weekly, followed by weekly maintenance dosing, in children with recurrent/refractory solid or CNS tumours.
详细描述
Eligible subjects enrolled in the study will receive EEDVSMit by IV injection twice weekly as a 20 min infusion beginning at study day 1 for the first cycle (4 weeks) then weekly for subsequent cycles. Subjects will undergo radiological assessment of their tumours after the first cycle, and every second cycle thereafter. Dosing with EEDVSmit will continue unless there is radiographic evidence of progressive disease (PD) per RECIST criteria version 1.1, the subject becomes intolerant to the study medication, signs and symptoms of clinical progression are evident as determined by the principal investigator, or the subject/parent/guardian withdraws consent. Suspected tumour progression should be confirmed with a repeat scan after 4 weeks to exclude the possibility of pseudoprogression.
Determination of EGFR expression for eligibility of subjects will be assessed at the local site. In addition, radiological assessment confirming measurable disease by the RECIST criteria is also required for entry into the Part B of the study.
The study will be conducted in two parts: Part A -Dose Exploration and Part B -Dose Expansion.
Part A - Dose Exploration:
The dose exploration part of the study is aimed at determining a recommended phase 2 dose (RP2D) in this patient group. A standard dose escalation with a rolling 6 design will be used.
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
- 2 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be ≥ 2 years and ≤ 21 years old at the time of study enrolment.
- •Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age
- •Patients must have relapsed or refractory solid or CNS tumours or have a diagnosis of DIPG. Patients must have had histologic verification of malignancy at original diagnosis or relapse, or a diagnosis of DIPG by MRI imaging.
- •Patients must have either measurable or evaluable disease for Part B of the study only
- •Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
- •Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
排除标准
- •Pregnant or breast-feeding women will not be entered on this study.
- •Any active uncontrolled infection
- •Patients who are known to be serologically positive for Hepatitis A, B or C, or have a history of liver disease, other forms of hepatitis or cirrhosis.
- •Known positive test for human immunodeficiency virus infection
- •Patients with disease of any major organ system that would compromise their ability to withstand therapy
- •Concurrent or prior (within 7 days of enrolment) anticoagulation therapy, except low molecular weight heparins or low dose aspirin
- •Patients receiving corticosteroids must be on a stable dose that has not been increased for at least 7 days prior to study enrolment.
- •Patients who are currently receiving another investigational drug are ineligible.
- •Patients who are currently receiving other antineoplastic agents are ineligible.
- •All herbal supplements, vitamins, and nutritional supplements taken within the last 30 days prior to dosing on Day 1 (and continued use, if appropriate), must be reviewed and approved by the Study Chair.
- •Patient will not be available for protocol-required study visits or procedures, to the best of the subject/parent/guardian's and investigator's knowledge.
- •Patient has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject/parent/guardian to give written informed consent and/or to comply with all required study procedures.
- •History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
- •Patients will be screened for antibodies to S. typhimurium and will not be eligible until antibodies are non-detectable
- •Patients will be screened for IL6 and TNFa cytokines and will not be eligible until levels are less than 3x times the detectable limit of the assay.
研究组 & 干预措施
Mitoxantrone packaged EDV
Mitoxantrone packaged EDV (EnGeneIC Dream Vector)
干预措施: Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle) (Drug)
结局指标
主要结局
MTD at which fewer than one third of patients experience dose limiting toxicity as assessed by CTCAE v4.0
时间窗: Day 28 (cycle 1)
To determine a recommended phase 2 dose (RP2D) for EEDVsMit administered intravenously in children with recurrent / refractory solid or CNS tumours expressing EGFR
Incidence of treatment-related adverse events as assessed by CTCAE v4.0
时间窗: Up to 35 days after the completion of study treatment
To define and describe the toxicities of EEDVSMit administered on these schedules in children with recurrent/refractory solid or CNS tumours
Incidence of all adverse events as assessed by CTCAE v4.0, clinically significant changes in vital signs, ECGs and clinical laboratory tests
时间窗: Up to 35 days after the completion of study treatment
Assess the safety and tolerability of EEDVSMit in children with recurrent/refractory solid or CNS tumours.
次要结局
- Assess disease response according to RECIST version 1.1 for children with recurrent/refractory solid or CNS tumours(Up to 35 days after the completion of study treatment)
- Assess overall survival(12 months from the date the last subject was enrolled in the study.)
- Time to response assessed by radiological imaging and RECIST v1.1(Evaluated at Day 56 (after cycle 2), then every second cycle to the end of study treatment (up to 12 months))
研究者
Dr David Ziegler
Chief Investigator
Sydney Children's Hospitals Network