ZHAN QIONG, MD

liang xiaohua, phD

The purpose of this study is to elucidate the pharmacokinetics and the blood-brain barrier penetration of the elemene.

Blood Brain Barrier Penetration and Pharmacokinetics of the Elemene in Malignant Patients.

Dalian Holley Kingkong Pharmaceutical Co., Ltd

Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Primary Liver Cancer

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Oxaliplatin

Liver Extracts

the group treated with the Elemene Injection/Elemene Oral Emulsion in Combination with Systematic Chemotherapy including Oxaliplatin

the group treated with Systematic Chemotherapy including Oxaliplatin

Elemene

Shukui Qin

Yinying Lu

Da Zhao

Yonghui An

Yuxian Bai

Huaimin Liu

Xianglin Yuan

Tao Zhang

Baochen Wang

Wensheng Qiu

Jin Li

Clinical Trial of Elemene Injection/Elemene Oral Emulsion in Combination with Systematic Chemotherapy including Oxaliplatin in the First -line treatment of advanced primary liver cancer

Patients with advanced primary liver cancer will be enrolled in the trial , then separated randomly into two group. One group treated with the Elemene Injection/Elemene Oral Emulsion in Combination with Systematic Chemotherapy including Oxaliplatin , another group treated with Systematic Chemotherapy including Oxaliplatin. The purpose of the study is to evaluate the effect and safety of the Elemene Injection/Elemene Oral Emulsion in Combination with Systematic Chemotherapy including Oxaliplatin in the First -line treatment of advanced primary liver cancer

One group treated with the Elemene Injection/Elemene Oral Emulusion in Combination with Systematic Chemotherapy including Oxaliplatin , another group treated with Systematic Chemotherapy including Oxaliplatin.

Clinical Trial of Elemene in Combination With Oxaliplatinin the Treatment of Advanced Primary Liver Cancer

Clinical Trial of Elemene Injection/Elemene Oral Emulsion in Combination With Systematic Chemotherapy Including Oxaliplatin in the First -Line Treatment of Advanced Primary Liver Cancer

Objective response rate.The proportion of patients who had a best response rating of complete response and partial response.

Disease control rate.The proportion of patients who had a best response rating of complete response, partial response, or stable disease.

Progression-free survival.The time of patients from randomization to death caused by the progression of the tumor or any cause

Overall survival.The time of patient from randomization to death caused by any cause

BeiJing Yijiayi Medicine Techonoloy Co., Ltd.

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

Maintenance chemotherapy with TMZ will be administered at 150-200 mg/m2/day for 5 days in each 28-day cycle.

Elemene injectable emulsion will be given for 80 mg/day in each 14-day cycle.

Maintenance chemotherapy with TMZ will be administered at 150 mg/m2/day for 5 days in each 28-day cycle.

Jianmin Zhang, MD

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.

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.

Pilot Study of Elemene in Treating Patients With Refractory Glioblastoma

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

Kaplan Meier methods will be used to estimate median OS.

Kaplan Meier methods will be used to estimate median PFS. Progression is defined by Response Assessment in Neuro-Oncology (RANO) criteria.

Objective Response Rate (ORR) will be assessed by comparison with baseline magnetic resonance imaging by RANO.

Complete Response (CR) is disappearance of all measurable and non-measurable disease for at least 4 weeks.

Partial Response (PR) is ≥ 50% decrease in lesions for at least 4 weeks.

Duration of Response (DOR) is the time between the initial response to the treatment and subsequent disease progression.

Hangzhou Normal University

Second Affiliated Hospital, School of Medicine, Zhejiang University

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Adenocarcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Amino Acids

Osimertinib

Tyrosine Kinase Inhibitors

Erlotinib Hydrochloride

Gefitinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Elemene Injectable Emulsion sequentially with Elemene Oral Emulsion plus First -generation EGFR-TKIs (Gefitinib,Erlotinib, Icotinib) or Third-generation EGFR-TKIs (including but not limited to Osimertinib, Almonertinib, Furmonertinib).

First-generation EGFR-TKIs (Gefitinib,Erlotinib, Icotinib) or third-generation EGFR-TKIs (including but not limited to Osimertinib, Almonertinib, Furmonertinib).

Elemene Injectable Emulsion: 20ml: 88mg, 6 injections each time, once a day, continuous intravenous drip for 5 days. Continue to use Elemene Oral Emulsion. For specific usage, refer to the drug label.

Elemene Oral Emulsion: 20ml: 176mg, 1 dose each time, 3 times a day. Use the Elemene Oral Emulsions until the disease progresses, the intolerable toxicity, the patient withdraws from the study, or dies for any reason.

First or third generation EGFR-TKIs: refer to the drug label.

Elemene plus first or third generation EGFR-TKIs

First or third generation EGFR-TKIs

Tian Xie, PhD

Kaifeng Wang, PhD

Hongyu Zhao

Qinghua Gao

Qi Li

Bing Wei

Ke Xie

Jiyuan Ding

Ziping Wang

Ziping Wang, PhD

This is a nationwide, multicenter and prospective cohort study. The purpose of this study is to evaluate the synergistic effect and safety of Elemene plus TKIs in EGFR-mutated advanced non-small cell lung cancer.

About 9.2%-45.8% of Chinese patients with Non-small cell lung cancer were positive for EGFR gene mutation. Gefitinib, Erlotinib, Icotinib, Afatinib showed efficacy superior to that of chemotherapy in the treatment of EGFR mutation positive advanced NSCLC, and lower rates of serious adverse events. However, after a median of 8 to 13 months of disease control, patients ultimately progress due to acquired resistance of EGFR-TKIs. Elemene, a chemotherapeutic isolated from the Chinese medicinal herb Rhizoma Zedoariae, has been shown to have a comprehensive anti-tumor effect and the potential effect on reversing drug resistance.

In this study, about 22 research centers will participate in. We planned to enroll 744 patients with advanced non-small cell lung adenocarcinoma who were positive for EGFR mutations. The dynamic random method will be adopted in this study. Patients will be randomly divided into the experimental group（Elemene plus first or third generation EGFR-TKIs), and control group (First or third generation EGFR-TKIs, only). The purpose of this study is evaluating the synergistic effect and safety of Elemene plus TKIs in EGFR-mutated advanced non-small cell lung cancer. We also try to analyze the correlation between molecular biomarkers and patient prognosis, including but not limited to drug-resistant genes and circulating tumor cells.

Synergistic Effect of Elemene Plus TKIs Compared With TKIs in EGFR-mutated Advanced NSCLC：Prospective Study

Synergistic Real-World Study and Evidence-based Medicine Evaluation of Elemene Combined With Tyrosine Kinase Inhibitors（TKIs）in the Treatment of Advanced Non-small Cell Lung Cancer (NSCLC): Prospective Study

Quality of Life (QOL) was measured using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30 + LC 13).

KPS: Performance status were measured using Karnofsky Performance Scale (KPS)

TCM symptom score: Traditional Chinese Medical symptoms were measured from these eight aspects: chest pain, oppression in the chest, blood stasis, shortness of breath, weakness, palpitations, dry mouth, vexation. Particular attention should be paid to chest pain and weakness.

Including but not limited to drug-resistant genes and circulating tumor cells. Such as PD-L1、MSI-H/dMMR、TMB、HLA、POLE、POLD1、DDR、TP53、KRAS、BRCA2、PBRM1、MDM2/4、EGFR、ALK、PTEN、JAK1/2、DNMT3A、STK11.

PFS was defined as the interval from the date of randomization to the date of the first evidence of disease progression or death, whichever occurs first. Disease progression was defined according to RECIST 1.1.

ORR was defined as the percentage of participants with the best overall response (BOR) of complete response (CR) or partial response (PR) based on RECIST 1.1.

Disease Control Rate (DCR) = Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) as defined by RECIST 1.1.

Overall survival (OS) was defined as the interval from the date of randomization to date of death from any cause, or the date of last known follow-up alive.

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

A serious adverse event (experience) or reaction is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect

All noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions.

A SADR is a serious ADR according to the above criteria of SAE.

LinkDoc Technology (Beijing) Co. Ltd.

Tian Xie

Professor

Patients receive maximal safe tumor resection, concurrent radiochemotherapy with TMZ, and adjuvant TMZ (the Stupp Protocol). Placebo that has the same appearance and flavor with Elemene is given 20ml orally, three times a day for 28 consecutive days (as one cycle) for 6 cycles, during the phase of adjuvant TMZ administration.

Patients receive maximal safe tumor resection, concurrent radiochemotherapy with TMZ, and adjuvant TMZ (the Stupp Protocol). Elemene is given 20ml:176mg orally, three times a day for 28 consecutive days (as one cycle) for 6 cycles, during the phase of adjuvant TMZ administration.

Elemene of 20ml is given orally, three times a day, for 28 consecutive days (as a cycle), for 6 cycles.

Placebo (with the same appearance and flavor with Elemene) of 20ml is given orally, three times a day, for 28 consecutive days (as a cycle), for 6 cycles.

Placebo

Yu Wang, MD, PhD

Xiaopeng Guo, MD

Wenbin Ma, MD

Yu Wang, MD, PHD

The goal of this phase II randomized clinical trial is to compare the safety and efficacy of Elemene plus Stupp Protocol (the new protocol) and Stupp Protocol alone (the standard protocol) in patients with newly-diagnosed glioblastomas (ndGBMs). The main questions to answer are:

* Whether the new treatment protocol (Elemene plus Stupp Protocol) is clinically safe for ndGBM patients.
* Whether the new treatment protocol (Elemene plus Stupp Protocol) brings better survival benefits for ndGBM patients compared to the standard-of-care Stupp Protocol.

Study participants will be enrolled in 5 hospitals in China and randomly assigned to receive either the new protocol or the standard protocol. The overall survival (OS) rate in the 12th month, the progression-free survival (PFS) rate in the 6th month, OS, PFS, and adverse events assessed by the CTCAE (Common Terminology Criteria for Adverse Events) will be evaluated for all patients.

Glioblastoma (GBM) is a WHO grade 4 adult-type diffuse glioma and the most common malignant, primary brain tumor with a 5-year overall survival (OS) of only \~5% in real-world studies. The Stupp Protocol, consisting of fractionated focal irradiation in daily fractions of 2 Gy given 5 days/week for 6 weeks (a total of 60 Gy), plus concomitant daily temozolomide (TMZ, 75 mg/m2/day, 7 days/week from the first to the last day of radiotherapy) after maximal safe tumor resection, followed by six cycles of adjuvant TMZ (150-200 mg/m2/day for 5 days during each 28-day cycle), has been adopted as the standard of care for patients with newly-diagnosed GBMs (ndGBMs) since 2005.

However, there have been no other treatment modalities except for tumor treating fields (TTFields) that have brought survival benefits for ndGBM patients during the past two decades. Since TTFields therapy is super expensive (about 1 million yuan/0.15 million dollars per year) and fewer than 10% of ndGBM patients can afford it around the globe, the Stupp Protocol is still being used as the first-line and the most widely-adopted treatment option for ndGBM patients around the world.

Elemene, a Chinese anti-tumor medicine extracted from the plant Curcuma Wenyujin, has been isolated as a monomeric drug and has a broad-spectrum anti-tumor effect in various cancers, such as lung cancer, breast carcinoma, leukemia, and ovarian cancer. In recent years, its application in GBMs as revealed in the preliminary retrospective studies published in Chinese Journals and a few English Journals have shown survival benefits with acceptable toxicity. Elemene can pass through the blood-brain barrier because of its small molecular weight and lipid solubility and has synergistic anti-tumor effects with TMZ and radiotherapy for GBM patients. Several in vitro studies also have shown that Elemene could inhibit GBM cell proliferation, promote cell differentiation, and induce cancer cell apoptosis.

All these findings from the above studies have indicated the potential survival benefits of Elemene in treating ndGBMs. However, so far, no clinical trials have tested the efficacy and safety of the new treatment protocol (Elemene added to the Stupp Protocol) for ndGBMs compared with the conventional Stupp protocol.

In this study, the investigators aimed to launch a multi-center, phase II, randomized, controlled clinical trial to test the safety and efficacy of Elemene plus Stupp Protocol compared with Stupp Protocol alone for ndGBM patients.

Elemene Plus Stupp Protocol Versus Stupp Protocol Alone for Newly-diagnosed Glioblastoma

Efficacy and Safety of Elemene Plus Stupp Protocol Versus Stupp Protocol Alone for Newly-diagnosed Glioblastoma: A Multi-center Phase II Randomized Controlled Trial

Individual participant data (IPD) can be made available upon publication.

Subgroups to be divided by sex, age, molecular alterations, KPS score, and extent of resection.

The rate of patients who are still alive in the 12th month after randomization

The survival time from randomization to death from any cause

The survival time from randomization to objective tumor progression or death

The rate of patients who have no objective tumor progression in the 6th month after randomization

Adverse events evaluated using the CTCAE version 4.03

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Blood Brain Barrier Penetration and Pharmacokinetics of the Elemene in Malignant Patients.	NCT01679847	Cancer		-	Dalian Holley Kingkong Pharmaceutical Co., Ltd
Clinical Trial of Elemene in Combination With Oxaliplatinin the Treatment of Advanced Primary Liver Cancer	NCT03166553	Advanced Primar...	Elemene	18 Years - 75 Years	BeiJing Yijiayi Medicine Techonoloy Co., Ltd.
Pilot Study of Elemene in Treating Patients With Refractory Glioblastoma	NCT04674527	Refractory Glio...	Elemene Temozolomide	18 Years -	Second Affiliated Hospital, School of Medicine, Zhejiang University
Synergistic Effect of Elemene Plus TKIs Compared With TKIs in EGFR-mutated Advanced NSCLC：Prospective Study	NCT04401059	Carcinoma Non-Small-Cell ... Adenocarcinoma	Elemene plus fi... First or third ...	18 Years -	Hangzhou Normal University
Elemene Plus Stupp Protocol Versus Stupp Protocol Alone for Newly-diagnosed Glioblastoma	NCT05842746	Glioblastoma, I...	Elemene Placebo	18 Years - 70 Years	Peking Union Medical College Hospital

Spots Global Cancer Trial Database for elemene

Every month we try and update this database with for elemene cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for elemene

Every month we try and update this database with for elemene cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for elemene cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.