ESP1/SARC025 Global Collaboration: A Phase I Study of a Combination of the PARP Inhibitor, Niraparib and Temozolomide and/or Irinotecan in Patients With Previously Treated,Incurable Ewing Sarcoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 5
- 主要终点
- Dose-limiting toxicity and maximum tolerated dose
研究概览
简要总结
The purpose of this study is to define the dose-limiting toxicities and maximum tolerated dose of the poly ADP-ribose polymerase inhibitor niraparib and escalating doses of temozolomide and/or irinotecan in patients with pre-treated incurable Ewing sarcoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 13 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed Ewing sarcoma
- •Evidence of Ewing sarcoma translocation by FISH or RT-PCR.
- •Must be willing to undergo tumor biopsy at study entry for biologic correlates.
- •If patient > 18 years, must be willing to undergo on-treatment tumor biopsy unless medically contra-indicated
- •Recurrent or refractory tumors with no known curative treatment options according to the judgment of the investigator.
- •Age ≥ 13 years.
- •Life expectancy of ≥ 3 months.
- •ECOG performance status 0-
- •Measurable disease on CT or MRI by RECIST 1.
- •Adequate organ function
- •Patients must have received as a minimum a first line chemotherapy regimen consisting of at least 2 of the following agents: doxorubicin, cyclophosphamide, ifosfamide, etoposide.
- •Time elapsed from previous therapy must be ≥ 3 weeks for systemic therapy, ≥ 2 weeks for radiation therapy or major surgery.
- •Patients who have undergone autologous hematopoietic stem cell transplantation are eligible once they have recovered from all toxicities from therapy
- •Patients who have received allogeneic hematopoietic stem cell transplantation will be eligible 6 months after the procedure provided there is no evidence of active graft-versus-host disease and immunosuppressive treatment has been discontinued for at least 30 days.
- •Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of central nervous system metastatic disease, have been off glucocorticoids for at least 4 weeks, have no overt evidence of neurological deficit and are ≥ 6 weeks from completion of brain irradiation.
- •Patients or their legal representative (if the patient is < 18 years old) must be able to read, understand and provide written informed consent to participate in the trial.
- •Females of childbearing potential as well as males and their partners must agree to use an effective form of contraception during the study and for 6 months following the last dose of study medication.
排除标准
- •Clinically significant unrelated illness which would, in the judgment of the treating physician, compromise the patient's ability to tolerate the investigational agent or be likely to interfere with the study procedures or results.
- •Patients with baseline QTc > 480 msec.
- •Inability to swallow capsules.
- •Known hypersensitivity to any of the components of niraparib or prior hypersensitivity reactions to that class of drugs.
- •Known hypersensitivity reaction to temozolomide or any of its components, or dacarbazine (DTIC) if enrolled on ARM 1 or irinotecan or any of its components if enrolled on ARM 2
- •Concomitant use of any other investigational or anticancer agent(s).
- •Pregnant patients or patients who are breast feeding. Subjects capable of pregnancy (post menarche and not post-menopausal, defined as over 12 months since final menstrual period) must have a negative pregnancy test within 7 days prior to first dose.
- •Other clinically significant malignant disease diagnosed within the previous 5 years, excluding intra-epithelial cervical neoplasia or non-melanoma skin cancer.
- •Active central nervous system disease.
- •Known history of MDS or AML
- •Known persistent (> 4 weeks) ≥ Grade 2 neutropenia, ≥ Grade 2 thrombocytopenia or > Grade 3 anemia from prior cancer therapy
研究组 & 干预措施
niraparib and irinotecan
Niraparib will be taken orally and irinotecan will be administered intravenously.
干预措施: niraparib (Drug)
niraparib and temozolomide
Niraparib (capsule) and temozolomide (capsule) will be taken together.
干预措施: Temozolomide (Drug)
niraparib and temozolomide
Niraparib (capsule) and temozolomide (capsule) will be taken together.
干预措施: niraparib (Drug)
niraparib and irinotecan
Niraparib will be taken orally and irinotecan will be administered intravenously.
干预措施: Irinotecan (Drug)
niraparib, irinotecan and temozolomide
Niraparib and temozolomide will be taken orally. Irinotecan will be administered intravenously.
干预措施: niraparib (Drug)
niraparib, irinotecan and temozolomide
Niraparib and temozolomide will be taken orally. Irinotecan will be administered intravenously.
干预措施: Temozolomide (Drug)
niraparib, irinotecan and temozolomide
Niraparib and temozolomide will be taken orally. Irinotecan will be administered intravenously.
干预措施: Irinotecan (Drug)
结局指标
主要结局
Dose-limiting toxicity and maximum tolerated dose
时间窗: Approximately 24 months
Dose limiting toxicity describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. The maximum tolerated dose is the highest dose of a drug or treatment that does not cause unacceptable side effects.
次要结局
- Tumor response rate(Approximately 24 months)
- Duration of response(Approximately 24 months)
- Progression-free survival(Month 4 and 6)