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Synergistic Effect of Elemene Plus TKIs Compared With TKIs in EGFR-mutated Advanced NSCLC：Prospective Study (SELECT-2)

Primary Purpose

Carcinoma, Non-Small-Cell Lung Cancer, Adenocarcinoma

Status

Recruiting

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Elemene plus first or third generation EGFR-TKIs

First or third generation EGFR-TKIs

About this trial

This is an interventional treatment trial for Carcinoma focused on measuring Elemene, TKI, EGFR, Real-world study

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age ≥ 18.
Histologically or cytologically confirmed advanced non-small cell lung adenocarcinoma(stage IIIB~IV).
Patients with EGFR mutations (deletions in exon 19 and L858R in exon 21 of the EGFR gene), plan to receive First-generation EGFR-TKIs (Gefitinib, Erlotinib, Icotinib) or third generation EGFR-TKIs (including but not limited to Osimertinib, Almonertinib, Furmonertinib) monotherapy for the first time (patients who have been using first- or third-generation EGFR-TKIs for less than 28 days can be enrolled).
Patients positive for EGFR gene mutation (deletions in exon 19 and L858R in exon 21 of the EGFR gene), with disease progression after receiving chemotherapy can be enrolled.
Confirmed by investigators, tumor tissue can't be surgically excised.
No prior exposure to elemene injectable and/or oral emulsion within one month.
Prior exposure to other Chinese patent medicine with similar efficacy within one month. If more than one month, patients can be enrolled after a 30-day washout period (without continuing to use the above medications).
The participant must be capable of understanding and complying with the protocol and willing to sign a written informed consent document.

Exclusion Criteria:

Patients with any EGFR mutations other than 19DEL or 21L858R.
Accompanied by other active tumors. (Except for stable basal cell carcinoma after treatment， If metachronous tumors have been controlled, participating was allowed )
Exposure to First- or third-generation EGFR-TKIs combined treatment, for example, chemotherapy, anti-angiogenesis therapy.
Receiving radiotherapy or chemotherapy.
Pregnant or lactating women.
Allergic to Elemene.
Participating in other drug clinical trials.
Refuse to comply with the follow-up.
The researchers did not consider it appropriate to participate in this study for other reasons.

Sites / Locations

Affiliated Hospital of Nantong UniversityRecruiting
Panjin Central HospitalRecruiting
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineRecruiting
The Second People's Hospital of Yangcheng CountyRecruiting
Sichuan Academy of Medical Sciences· Sichuan Province People's HospitalRecruiting
Hangzhou Cancer HospitalRecruiting
Peking University Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Elemene plus First or Third generation EGFR-TKIs

First or third generation EGFR-TKIs only

Arm Description

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).

Outcomes

Primary Outcome Measures

PFS

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.

Secondary Outcome Measures

ORR

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.

DCR

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.

Incidence and severity of AE or SAE

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

Incidence and severity of ADR or SADR

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.

Full Information

NCT ID

NCT04401059

First Posted

May 18, 2020

Last Updated

May 15, 2023

Sponsor

Tian Xie

Collaborators

LinkDoc Technology (Beijing) Co. Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04401059

Brief Title

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

Acronym

SELECT-2

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 9, 2020 (Actual)

Primary Completion Date

September 30, 2025 (Anticipated)

Study Completion Date

March 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Tian Xie

Collaborators

LinkDoc Technology (Beijing) Co. Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Non-Small-Cell Lung Cancer, Adenocarcinoma

Keywords

Elemene, TKI, EGFR, Real-world study

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

744 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Elemene plus First or Third generation EGFR-TKIs

Arm Type

Experimental

Arm Description

Arm Title

First or third generation EGFR-TKIs only

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Elemene plus first or third generation EGFR-TKIs

Other Intervention Name(s)

H10960114, H20010338

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

First or third generation EGFR-TKIs

Other Intervention Name(s)

Gefitinib(Iressa,YiRuiKe), Erlotinib(Tarceva), Icotinib(Kaimeina), Osimertinib(Tagrisso), Almonertinib, Furmonertinib, etc.

Intervention Description

refer to the drug label.

Primary Outcome Measure Information:

Title

PFS

Description

Time Frame

Start of treatment until 1-year follow-up

Secondary Outcome Measure Information:

Title

ORR

Description

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.

Time Frame

Start of treatment until 1-year follow-up

Title

DCR

Description

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

Time Frame

Start of treatment until 1-year follow-up

Title

Description

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.

Time Frame

Start of treatment until 1-year follow-up

Title

Incidence and severity of AE or SAE

Description

Time Frame

Start of treatment until 30 days after the last treatment

Title

Incidence and severity of ADR or SADR

Description

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.

Time Frame

Start of treatment until 30 days after the last treatment

Other Pre-specified Outcome Measures:

Title

Quality of life (QOL)

Description

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).

Time Frame

Start of treatment until 1-year follow-up

Title

Karnofsky Performance Scale (KPS)

Description

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

Time Frame

Start of treatment until 1-year follow-up

Title

Traditional Chinese Medical(TCM) symptoms score

Description

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.

Time Frame

Start of treatment until 1-year follow-up

Title

Molecular biomarkers

Description

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.

Time Frame

Start of treatment until 1-year follow-up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥ 18. Histologically or cytologically confirmed advanced non-small cell lung adenocarcinoma(stage IIIB~IV). Patients with EGFR mutations (deletions in exon 19 and L858R in exon 21 of the EGFR gene), plan to receive First-generation EGFR-TKIs (Gefitinib, Erlotinib, Icotinib) or third generation EGFR-TKIs (including but not limited to Osimertinib, Almonertinib, Furmonertinib) monotherapy for the first time (patients who have been using first- or third-generation EGFR-TKIs for less than 28 days can be enrolled). Patients positive for EGFR gene mutation (deletions in exon 19 and L858R in exon 21 of the EGFR gene), with disease progression after receiving chemotherapy can be enrolled. Confirmed by investigators, tumor tissue can't be surgically excised. No prior exposure to elemene injectable and/or oral emulsion within one month. Prior exposure to other Chinese patent medicine with similar efficacy within one month. If more than one month, patients can be enrolled after a 30-day washout period (without continuing to use the above medications). The participant must be capable of understanding and complying with the protocol and willing to sign a written informed consent document. Exclusion Criteria: Patients with any EGFR mutations other than 19DEL or 21L858R. Accompanied by other active tumors. (Except for stable basal cell carcinoma after treatment， If metachronous tumors have been controlled, participating was allowed ) Exposure to First- or third-generation EGFR-TKIs combined treatment, for example, chemotherapy, anti-angiogenesis therapy. Receiving radiotherapy or chemotherapy. Pregnant or lactating women. Allergic to Elemene. Participating in other drug clinical trials. Refuse to comply with the follow-up. The researchers did not consider it appropriate to participate in this study for other reasons.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tian Xie, PhD

Phone

+86-13606707928

xbs@dljg.sina.net

First Name & Middle Initial & Last Name or Official Title & Degree

Kaifeng Wang, PhD

Phone

+86-13588088469

kaifengw@aliyun.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ziping Wang, PhD

Organizational Affiliation

Peking University Cancer Hospital & Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Affiliated Hospital of Nantong University

City

Nantong

State/Province

Jiangsu

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hongyu Zhao

Phone

+86-18255179769

Facility Name

Panjin Central Hospital

City

Panjin

State/Province

Liaoning

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Qinghua Gao

Phone

+86-18102487506

gaoqinghuawl@sohu.com

Facility Name

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

City

Shanghai

State/Province

Shanghai

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Qi Li

Phone

18521301790

Facility Name

The Second People's Hospital of Yangcheng County

City

Jincheng

State/Province

Shanxi

ZIP/Postal Code

048100

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bing Wei

Phone

13835633832

564943978@qq.com

Facility Name

Sichuan Academy of Medical Sciences· Sichuan Province People's Hospital

City

Chengdu

State/Province

Sichuan

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ke Xie

Phone

13008154897

Facility Name

Hangzhou Cancer Hospital

City

Hangzhou

State/Province

Zhejiang

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jiyuan Ding

Phone

+86-13575467709

Facility Name

Peking University Cancer Hospital

City

Beijing

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ziping Wang

Phone

+86-18322012056

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

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

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