Pilot Study of Elemene in Treating Patients With Refractory Glioblastoma

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Refractory Glioblastoma
• Intervention / Treatment: Drug: Elemene; Drug: Temozolomide

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jianmin Zhang, MD; Phone Number: 8613805722695; Email: 2307010@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Second Affiliated Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental group; 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; Elemene injectable emulsion will be given for 80 mg/day in each 14-day cycle.; Other Names: elemene injectable emulsion; Drug: Temozolomide; Maintenance chemotherapy with TMZ will be administered at 150 mg/m2/day for 5 days in each 28-day cycle.; Other Names: TMZ
Experimental: contral group; Maintenance chemotherapy with TMZ will be administered at 150-200 mg/m2/day for 5 days in each 28-day cycle.	Drug: Temozolomide; Maintenance chemotherapy with TMZ will be administered at 150 mg/m2/day for 5 days in each 28-day cycle.; Other Names: TMZ

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Hangzhou Normal University
• Investigators: Study Chair: Jianmin Zhang, MD, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: November 17, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 19, 2020

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: SAHZJU-RCT-ELEMENE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No