Evaluation of the Efficacy and Safety of Regorafenib in Patients With Refractory Primary Bone Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Assessment of the safety of regorafenib
研究概览
简要总结
The aim of the project is to improve treatment outcomes in patients with primary malignant bone tumors, refractory to standard therapy, by increasing the availability of advanced therapy, as well as to develop treatment options using advanced molecular diagnostics for patients who have not responded to the standard therapeutic regimen, and to introduce modern diagnostics for risk stratification and for the use in molecularly targeted therapies.
详细描述
The scope of the project is to cover the entire population of children, adolescents and young adults from the age of 9 to the age of 21, who progressed to first-line treatment or who presented with a recurrence of Ewing's sarcoma or osteosarcoma. Despite escalating doses of chemotherapy and radiotherapy, aggressive surgical procedures in patients with dissemination disease and negative prognostic factors, no improvement in treatment outcomes has been achieved for over 30 years. For this reason, other therapeutic options are being investigated. There have been no significant responses to immunotherapy. Although, the inclusion of tyrosine kinase inhibitors (TKIs) appears to be promising.
The identification of new mutations in bone tumors has led to a better insight into the molecular basis of these tumors, which has resulted in a more significant role of genetic research in everyday practice. Although traditional histopathological examinations are currently the basis for the diagnosis of bone tumors, the developing techniques of molecular biology make it possible, in many cases, to refine the diagnosis and, in the near future, will become the basis for the classification of these neoplasms. Moreover, these technics are expected to enable the qualification of patients to modern molecularly targeted therapies.
Based on the above data, the objectives of the project are as follows: 1. to estimate the nature and frequency of mutations in the tumor tissue, 2. to compare molecular test results with clinical data (which will allow for the initial assessment of the impact of the mutation status on the clinical condition, course of treatment and prognosis), 3. to include targeted treatment - broad spectrum tyrosine kinase inhibitor - regorafenib in standard therapy.
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
- 9 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >9 years ≤ 21 years.
- •Histologically proven Ewing sarcoma or osteosarcoma.
- •Failure of the treatment identified no earlier than 30 days prior to study treatment initiation (at least one of below needs to apply in order for this requirement to be satisfied):
- •progression on the I line or next, or
- •Signing of informed consent for trial participation (including for Regorafenib treatment) according with current legal regulations.
- •Life expectancy of at least 12 weeks from the time informed consent was signed.
- •Possibility of swallowing the tablet.
- •Consent to the use of effective contraception throughout the period of the study and a minimum of 2 year after discontinuation of study treatment in patients at puberty and sexual maturity.
排除标准
- •Lack of inclusion criteria
- •Previous treatment with Regorafenib.
- •Pregnancy and breastfeeding.
- •Hypersensitivity to the study drug or any of its ingredients.
- •Simultaneous treatment with other drugs which might interact with Regorafenib.
- •Persistent toxicity related to prior therapy, making it impossible to treat with Regorafenib.
- •Diagnosis of other malignancies before study inclusion.
- •Patients with uncontrolled hypertension.
- •Patients with diseases of the coagulation system.
- •Patients with heart defects and / or cardiac arrhythmias requiring permanent treatment with antiarrhythmic drugs.
- •Other acute or persistent disorders, behaviors or abnormal laboratory test results, which might increase the risk related to the participation in this clinical trial or to taking the study drug, or which might influence the interpretation of the study results, or which, in the investigator's opinion, disqualify a patient from participating in the trial.
研究组 & 干预措施
R1 - Regorafenib Arm
R1 - the experimental group. Standard oncological treatment will be started. Additionally, patients will receive regorafenib orally at doses adjusted for age, body surface area and pharmacokinetics. Treatment with regorafenib will be continued for up to 1 year or until disease progression, patient death, unacceptable toxicity, or study closure. Pharmacokinetics and safety profile of the investigational product (IP) will be determined throughout the course therapy.
干预措施: Regorafenib (Drug)
R2 - Control Group
R2 - the control group - will receive only standard treatment. In the event of progression or relapse, patients in the control group will have the option to receive the IP along with the standard treatment of the next line.
结局指标
主要结局
Assessment of the safety of regorafenib
时间窗: from date of randomization, until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months.
Safety will be assessed by analyzing recorded vital signs, laboratory test results, echocardiography, and ECG.
EFS - (Event-Free Survival).
时间窗: 1 year
To explore the efficacy in terms of EFS - (Event-Free Survival)
Determining the dose of the test substance in patients between 9 and 21 years of age, at which exposure to the drug will be similar to that recommended for adults.
时间窗: 1 year
Safety will be assessed by the rate of participants presenting with Adverse Events stratified by grade, category, affected organ or system, as number of serious adverse events (SAEs)
Assessment of safety in terms of AEs
时间窗: from date of randomization, until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months.
Safety will be assessed by the rate of participants presenting with Adverse Events stratified by grade, category, affected organ or system, as number of adverse events (AEs), including adverse events of special interest
次要结局
- ORR (Overall Response Rate).(Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.)
- Time to achieving sufficient drug concentration in serum.(Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.)
- Minimum serum concentration in steady state Cminss.(Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.)
- Maximum serum concentration in steady state Cmaxs.(Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.)
- Random serum concentration in steady state Css.(Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.)
- OS (Overall Survival).(Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.)
- Time to achieving steady state drug concentration in serum.(Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.)
- PFS (Progression-Free Survival).(Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.)
- Drug exposure Ctau.(Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.)
研究者
Anna Raciborska
Head od Department of Oncology and Surgical Oncology for Children and Youth; Prof. Ass. PhD MD
Institute of Mother and Child, Warsaw, Poland