Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated High Grade Malignant Peripheral Nerve Sheath Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 17
- 主要终点
- Number of Participants With Response Rate (Complete Response and Partial Response)
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as doxorubicin, ifosfamide, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy with or without radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating patients with stage III or stage IV malignant peripheral nerve sheath tumors.
详细描述
OBJECTIVES:
Primary
- Determine the clinical response rate (complete and partial) in patients with sporadic or neurofibromatosis type 1 (NF1)-associated high-grade stage III or IV malignant peripheral nerve sheath tumors (MPNSTs) after treatment with 4 courses of chemotherapy comprising doxorubicin hydrochloride and ifosfamide (IA) followed by etoposide and ifosfamide (IE).
Secondary
- Evaluate the utility of fludeoxyglucose F18 positron emission tomography (^18FDG-PET) and automated MRI volumetric tumor analysis as tools to assess response to treatment.
- Correlate response evaluation by 2-dimensional WHO criteria, 1-dimensional RECIST criteria, ^18FDG-PET, and volumetric MRI with percent necrosis in tumor specimens from patients who undergo surgery for local control after chemotherapy.
- Evaluate the response of plexiform neurofibroma(s) (if present) to chemotherapy using WHO criteria and automated volumetric MRI analysis.
- Evaluate the molecular biology of sporadic and NF1-associated MPNSTs by performing a detailed pathologic analysis of tumor samples with the goal to analyze if markers can be identified that predict for response to chemotherapy or outcome.
- Construct a tissue microarray from submitted tumor samples, that will be used in the future to identify novel targets for treatment of MPNSTs.
- Assess if a serum biomarker can be identified, that predicts for the presence of a MPNST versus benign plexiform neurofibroma.
- Increase the knowledge of the epidemiology and clinical presentation of NF1-associated MPNSTs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 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
Chemotherapy and local control by radiotherapy and surgery
Patients receive doxorubicin hydrochloride and ifosfamide (IA) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity. Patients then receive etoposide and ifosfamide (IE) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously (SC) after each chemotherapy course. After recovery from chemotherapy, patients undergo radiotherapy and receive 2 more courses of IE during radiotherapy followed by 2 more courses of IA after completion of radiotherapy. Some patients may then undergo surgery.
干预措施: filgrastim (Biological)
Chemotherapy and local control by radiotherapy and surgery
Patients receive doxorubicin hydrochloride and ifosfamide (IA) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity. Patients then receive etoposide and ifosfamide (IE) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously (SC) after each chemotherapy course. After recovery from chemotherapy, patients undergo radiotherapy and receive 2 more courses of IE during radiotherapy followed by 2 more courses of IA after completion of radiotherapy. Some patients may then undergo surgery.
干预措施: doxorubicin hydrochloride (Drug)
Chemotherapy and local control by radiotherapy and surgery
Patients receive doxorubicin hydrochloride and ifosfamide (IA) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity. Patients then receive etoposide and ifosfamide (IE) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously (SC) after each chemotherapy course. After recovery from chemotherapy, patients undergo radiotherapy and receive 2 more courses of IE during radiotherapy followed by 2 more courses of IA after completion of radiotherapy. Some patients may then undergo surgery.
干预措施: etoposide (Drug)
Chemotherapy and local control by surgery
Patients receive 2 courses of IA followed by 2 courses of IE as above. After recovery from chemotherapy, patients undergo surgery. After recovery from surgery, patients receive 2 more courses of IA followed by 2 more courses of IE in the absence of disease progression or unacceptable toxicity.
干预措施: ifosfamide (Drug)
Chemotherapy and local control by radiotherapy and surgery
Patients receive doxorubicin hydrochloride and ifosfamide (IA) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity. Patients then receive etoposide and ifosfamide (IE) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously (SC) after each chemotherapy course. After recovery from chemotherapy, patients undergo radiotherapy and receive 2 more courses of IE during radiotherapy followed by 2 more courses of IA after completion of radiotherapy. Some patients may then undergo surgery.
干预措施: ifosfamide (Drug)
Chemotherapy and local control by radiotherapy and surgery
Patients receive doxorubicin hydrochloride and ifosfamide (IA) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity. Patients then receive etoposide and ifosfamide (IE) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously (SC) after each chemotherapy course. After recovery from chemotherapy, patients undergo radiotherapy and receive 2 more courses of IE during radiotherapy followed by 2 more courses of IA after completion of radiotherapy. Some patients may then undergo surgery.
干预措施: conventional surgery (Procedure)
Chemotherapy and local control by radiotherapy and surgery
Patients receive doxorubicin hydrochloride and ifosfamide (IA) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity. Patients then receive etoposide and ifosfamide (IE) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously (SC) after each chemotherapy course. After recovery from chemotherapy, patients undergo radiotherapy and receive 2 more courses of IE during radiotherapy followed by 2 more courses of IA after completion of radiotherapy. Some patients may then undergo surgery.
干预措施: radiation therapy (Radiation)
Chemotherapy and local control by surgery
Patients receive 2 courses of IA followed by 2 courses of IE as above. After recovery from chemotherapy, patients undergo surgery. After recovery from surgery, patients receive 2 more courses of IA followed by 2 more courses of IE in the absence of disease progression or unacceptable toxicity.
干预措施: doxorubicin hydrochloride (Drug)
Chemotherapy and local control by surgery
Patients receive 2 courses of IA followed by 2 courses of IE as above. After recovery from chemotherapy, patients undergo surgery. After recovery from surgery, patients receive 2 more courses of IA followed by 2 more courses of IE in the absence of disease progression or unacceptable toxicity.
干预措施: etoposide (Drug)
Chemotherapy and local control by surgery
Patients receive 2 courses of IA followed by 2 courses of IE as above. After recovery from chemotherapy, patients undergo surgery. After recovery from surgery, patients receive 2 more courses of IA followed by 2 more courses of IE in the absence of disease progression or unacceptable toxicity.
干预措施: conventional surgery (Procedure)
结局指标
主要结局
Number of Participants With Response Rate (Complete Response and Partial Response)
时间窗: After 4 Cycles (1 cycle=21 days)
WHO criteria was used to determine responses due to the nonspherical shape of most MPNST. Complete Response (CR), Disappearance of all target lesions; Partial response (PR), \>=50% decrease of target lesions.
次要结局
- Identify the Number of Participants With a Serum Biomarker to Predict the Presence of MPNST Versus Benign Plexiform Neurofibroma(After 4 cycles)
- Utility of Fludeoxyglucose F18 Positron Emission Tomography (18FDG-PET) and Automated MRI Volumetric Tumor Analysis to Assess Response to Treatment(After 4 cycles)
- Response Evaluation Using WHO, RECIST, 18 FDG-PET and Volumetric MRI With Percent Necrosis in Tumor Specimens(After 4 cycles)
- Response of Plexiform Neurofibroma to Neoadjuvant Chemotherapy Using Volumetric MRI Analysis(After 4 Cycles (1 cycle=21 days))
- Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response(After 4 cycles)
- Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.(After 4 cycles)
- Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue(After 4 cycles)