Pilot Study of Elemene in Treating Patients With Refractory Glioblastoma

Study Overview
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Brief Summary
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This is a pilot phase I study to evaluate the safety and efficacy on elemene injectable emulsion in treating patients with glioblastoma. Elemene, isolated from the Chinese medicinal herb Curcuma wenyujin, was shown to exhibit antitumor activity in human and murine tumor cells in vitro and in vivo.Elemene injectable emulsion against malignant tumors was low. Therefore, the effect of Elemene injectable emulsion being used in clinical settings needs to be confirmed by further RCTs.

Detailed Description
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Background Elemene, isolated from the Chinese medicinal herb Curcuma wenyujin, was shown to exhibit antitumor activity in human and murine tumor cells in vitro and in vivo The study shows that the methodological quality of RCTs of Elemene injectable emulsion against malignant tumors was low. Therefore, the effect of Elemene injectable emulsion being used in clinical settings needs to be confirmed by further RCTs Objectives To evaluate the safety of Elemene injectable emulsion to treat Refractory Glioblastoma with TMZ To evaluate the efficacy of Elemene injectable emulsion to treat Refractory Glioblastoma with TMZ Design This clinical trail is a randomized controlled trial.In control group,patients will receive TMZ-chemotherapy.In experimental group,patients will receive elemene injectable emulsion and TMZ-chemotherapy at the same time.

Official Title
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A Pilot Study of Elemene Injectable Emulsion in Treating Patients With Refractory Glioblastoma

Conditions
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Refractory Glioblastoma

Intervention / Treatment
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* Drug: Elemene
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years; Male or Female. Relapsed/refractory disease confirmed by radiographic evidence after standard therapy. KPS ≥ 60 ≥ 8 weeks after completion of front-line radiation therapy ≥ 6 weeks after completion of nitrourea chemotherapy ≥ 14 days after completion of Temozolomide or other chemotherapy 2 weeks of wash-out time after completion of targeted therapy with related adverse events (AE) on baseline White blood cell count (WBC) ≥ 3.0 x 109/L; peripheral blood lymphocyte (PBL) ≥ 25%. Echocardiographic assessment of left ventricular ejection fraction (LVEF) ≥ 40% within 1 month of enrollment. Patients must be able to understand the investigational nature of the study and provide informed consent. Exclusion Criteria: Those who are allergic constitution, or have contraindications to CT and MRI1 contrast agents. Those who plan to receive any other anti-tumor treatment during the trial. Combined with serious primary diseases of cardiovascular, liver and kidney, and liver function (ALT, AST, Y-GT) exceeding 1.5 times of the upper limit: BUN or Cr exceeding 1.5 times of the upper limit of normal value. Patients with other malignant tumors. Those with active infections, etc. Suspected or confirmed a history of alcohol and drug abuse. Psychiatric illness, intellectual and language disabilities that compromise the informed consent process, at the discretion of the investigator. Women who are pregnant or nursing. Women of childbearing age who refuse to contraception. Active participation in another clinical treatment trials. According to the judgment of the investigator, other conditions that the plan cannot be followed.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br>Maintenance chemotherapy with TMZ will be administered at 150-200 mg/m2/day for 5 days in each 28-day cycle.And elemene injectable emulsion will be given for 80 -120 ml/day in each 14-day cycle or 21-day cycle. | Drug: Elemene<br>* Elemene injectable emulsion will be given for 80 mg/day in each 14-day cycle.<br>* Other names: elemene injectable emulsion;Drug: Temozolomide<br>* Maintenance chemotherapy with TMZ will be administered at 150 mg/m2/day for 5 days in each 28-day cycle.<br>* Other names: TMZ;|
| Experimental: contral group<br>Maintenance chemotherapy with TMZ will be administered at 150-200 mg/m2/day for 5 days in each 28-day cycle. | Drug: Temozolomide<br>* Maintenance chemotherapy with TMZ will be administered at 150 mg/m2/day for 5 days in each 28-day cycle.<br>* Other names: TMZ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival(OS) | Kaplan Meier methods will be used to estimate median OS. | 2 years. | 
| progression-free survival(PFS) | Kaplan Meier methods will be used to estimate median PFS. Progression is defined by Response Assessment in Neuro-Oncology (RANO) criteria. | 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate(ORR) | Objective Response Rate (ORR) will be assessed by comparison with baseline magnetic resonance imaging by RANO. | 2 years,up to 15 years if necessary. | 
| complete response(CR) | Complete Response (CR) is disappearance of all measurable and non-measurable disease for at least 4 weeks. | 2 years,up to 15 years if necessary. | 
| partial response | Partial Response (PR) is ≥ 50% decrease in lesions for at least 4 weeks. | 2 years,up to 15 years if necessary. | 
| duration of response | Duration of Response (DOR) is the time between the initial response to the treatment and subsequent disease progression. | 2 years,up to 15 years if necessary. |