Clinical trial NCT04401059: Synergistic Effect of Elemene Plus TKIs Compared With TKIs in EGFR-mutated Advanced NSCLC：Prospective Study
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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Carcinoma
Non-Small-Cell Lung Cancer
Adenocarcinoma
Keywords: Elemene
TKI
EGFR
Real-world study
Lead sponsor: Hangzhou Normal University
Sponsor class: OTHER
Collaborators: name: LinkDoc Technology (Beijing) Co. Ltd.
First posted: 2020-05-26
Enrollment: 744
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18.
2. Histologically or cytologically confirmed advanced non-small cell lung adenocarcinoma(stage IIIB\~IV).
3. 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).
4. 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.
5. Confirmed by investigators, tumor tissue can't be surgically excised.
6. No prior exposure to elemene injectable and/or oral emulsion within one month.
7. 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).
8. The participant must be capable of understanding and complying with the protocol and willing to sign a written informed consent document.

Exclusion Criteria:

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

Primary outcomes:
measure: PFS
timeFrame: Start of treatment until 1-year follow-up
Secondary outcomes:
measure: ORR
timeFrame: Start of treatment until 1-year follow-up
measure: DCR
timeFrame: Start of treatment until 1-year follow-up
measure: OS
timeFrame: Start of treatment until 1-year follow-up
measure: Incidence and severity of AE or SAE
timeFrame: Start of treatment until 30 days after the last treatment
measure: Incidence and severity of ADR or SADR
timeFrame: Start of treatment until 30 days after the last treatment
Other outcomes:
measure: Quality of life (QOL)
timeFrame: Start of treatment until 1-year follow-up
measure: Karnofsky Performance Scale (KPS)
timeFrame: Start of treatment until 1-year follow-up
measure: Traditional Chinese Medical(TCM) symptoms score
timeFrame: Start of treatment until 1-year follow-up
measure: Molecular biomarkers
timeFrame: Start of treatment until 1-year follow-up
Locations:
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
state: Jiangsu
city: Panjin
country: China
facility: Panjin Central Hospital
state: Liaoning
city: Shanghai
country: China
facility: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
state: Shanghai
city: Jincheng
country: China
facility: The Second People's Hospital of Yangcheng County
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Academy of Medical Sciences· Sichuan Province People's Hospital
state: Sichuan
city: Hangzhou
country: China
facility: Hangzhou Cancer Hospital
state: Zhejiang
city: Beijing
country: China
facility: Peking University Cancer Hospital
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Ziping Wang, PhD
role: PRINCIPAL_INVESTIGATOR
References: