A Phase II Study of Intrathecal and Systemic Chemotherapy With Radiation Therapy for Children With Central Nervous System Atypical Teratoid/Rhabdoid Tumor (AT/RT) Tumor
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 12
- 主要终点
- 2-yr Overall Survival
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving more than one chemotherapy drug with radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving intrathecal and systemic combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system (CNS) atypical teratoid/rhabdoid tumors.
详细描述
OBJECTIVES:
Primary
- Determine the efficacy of intensive systemic and intrathecal chemotherapy and radiotherapy, in terms of medial survival, in children with newly diagnosed central nervous system atypical teratoid/rhabdoid tumors in comparison with historical outcomes from prior trials.
Secondary
- Determine the toxicity profile and tolerability of this regimen in these patients.
- Determine the chemosensitivity of these patients' tumors by Magnetic Resonance Imaging (MRI) after an attempt at maximum surgical resection after 2 courses of this regimen.
- Determine the predictive value of the INI-1 gene mutation in determining prognosis by comparing tumor samples from patients with vs without this mutation treated with this regimen.
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
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: filgrastim (Biological)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: cisplatin (Drug)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: cyclophosphamide (Drug)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: cytarabine (Drug)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: dexrazoxane hydrochloride (Drug)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: doxorubicin hydrochloride (Drug)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: etoposide (Drug)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: leucovorin calcium (Drug)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: methotrexate (Drug)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: temozolomide (Drug)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: therapeutic hydrocortisone (Drug)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: vincristine sulfate (Drug)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: radiation therapy (Radiation)
Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)
Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.
Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.
Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
干预措施: Dactinomycin (Drug)
结局指标
主要结局
2-yr Overall Survival
时间窗: Patients are followed for survival up to 5 yrs post-therapy completion or death; As of this analysis, median follow-up among survivors was 31 months with the longest follow-up being 40 months.
Overall survival is defined as the time from date of diagnosis to death or date of last follow-up. 2-year overall survival is the probability of patients remaining alive at 2-years from study entry estimated using Kaplan-Meier (KM) methods which censors patients at date of last follow-up. Precision of this conditional probability estimate was measured in terms of standard error. Median OS, the original primary endpoint, was not estimable based on the Kaplan-Meier method because of insufficient follow-up.
次要结局
- Pre-Radiation Therapy Chemotherapeutic Response(Assessed at study entry and pre-RT/post-CT at week 7.)
研究者
Mark W. Kieran, MD, PhD
Principal Investigator
Dana-Farber Cancer Institute