Pilot Study of Elemene in Treating Patients With Refractory Glioblastoma

Phase 2

• Conditions: Refractory Glioblastoma
• Interventions: Drug: Temozolomide; Drug: Elemene

• Registration Number: NCT04674527
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-11-17
• Status Verified: 2020-12
• Study First Submitted QC: 2020-12-16
• Last Update Submitted: 2020-12-16
• Study First Posted: 2020-12-19
• Last Update Posted: 2020-12-19
• Study Start: 2021-06-01
• Primary Completion: 2023-06-01
• Study Completion: 2023-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Age ≥ 18 years; Male or Female.
2. Relapsed/refractory disease confirmed by radiographic evidence after standard therapy.
3. KPS ≥ 60
4. ≥ 8 weeks after completion of front-line radiation therapy
5. ≥ 6 weeks after completion of nitrourea chemotherapy
6. ≥ 14 days after completion of Temozolomide or other chemotherapy
7. 2 weeks of wash-out time after completion of targeted therapy with related adverse events (AE) on baseline
8. White blood cell count (WBC) ≥ 3.0 x 109/L; peripheral blood lymphocyte (PBL) ≥ 25%.
9. Echocardiographic assessment of left ventricular ejection fraction (LVEF) ≥ 40% within 1 month of enrollment.
10. Patients must be able to understand the investigational nature of the study and provide informed consent.

Exclusion Criteria

1. Those who are allergic constitution, or have contraindications to CT and MRI1 contrast agents.
2. Those who plan to receive any other anti-tumor treatment during the trial.
3. 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.
4. Patients with other malignant tumors.
5. Those with active infections, etc.
6. Suspected or confirmed a history of alcohol and drug abuse.
7. Psychiatric illness, intellectual and language disabilities that compromise the informed consent process, at the discretion of the investigator.
8. Women who are pregnant or nursing.
9. Women of childbearing age who refuse to contraception.
10. Active participation in another clinical treatment trials.
11. According to the judgment of the investigator, other conditions that the plan cannot be followed.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
contral group	Temozolomide	Maintenance chemotherapy with TMZ will be administered at 150-200 mg/m2/day for 5 days in each 28-day cycle.
experimental group	Elemene	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.
experimental group	Temozolomide	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Second Affiliated Hospital, School of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China