Clinical trial NCT03123484: β-elemene Combine With EGFR-TKI for Advanced EGFR-TKI-resistant NSCLC
Official title: β-elemene Combine With EGFR-TKI for Advanced EGFR-TKI-resistant Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: beta-elemene
Lead sponsor: China Medical University, China
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital of Dalian Medical University
name: The Second Affiliated Hospital of Dalian Medical University
name: Liaoning Cancer Hospital & Institute
name: Shengjing Hospital
name: General Hospital of Shenyang Military Region
First posted: 2017-04-21
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Epidermal Growth Factor Receptor tyrosine-kinase inhibitors （EGFR-TKIs）, including gefitinib，erlotinib and icotinib demonstrate excellent effect on the treatment of non small cell lung cancer (NSCLC) patients with EGFR mutations. However, patients who are initially sensitive to the drugs eventually become resistance. In this study, the investigators aim to explore the efficacy of beta-elemene, combining with EGFR-TKI in advanced non-small cell lung cancer with EGFR-TKI resistance.

Detailed description: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib，erlotinib and icotinib demonstrate excellent effect on the treatment of non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, patients who are initially sensitive to the drugs eventually become resistance. Beta-elemene, a natural plant drug extracted from Curcuma wenyujin, has been used as an antitumor drug for different tumors, including NSCLC via mechanism that inhibits Ras/Mapk signaling and cell cycle progression.In this study, the investigators aim to explore the efficacy of beta-elemene, combining with EGFR-TKI in advanced non-small cell lung cancer with EGFR-TKI resistance.

main objectives: progression-free survival (PFS) ratio in 12 week the secondary goal: Objective Response Rate （ORR）

Eligibility criteria: Inclusion Criteria:

1. Obtain of informed consent.
2. Histologically or cytologically confirmed, inoperable, recurrence or metastasis advanced non-small cell lung cancer (TNM Stage ⅢB or stage Ⅳ), took EGFR-TKI longer than 6 months and appeared disease progression.
3. At least one measurable lesion (helical CT scan long diameter ≥10mm, meet the requirements of the standard Response Evaluation Criteria In Solid Tumors（RESCIST） version 1.1).
4. Eastern Cooperative Oncology Group（ECOG）Performance Status（PS） :0-2.
5. Aged from 18 to 75 years (18 and 75 years are included).
6. Life expectancy ≥12 weeks.
7. Adequate bone marrow reserve and organ function as follows:

   Absolute neutrophils count (ANC) ≥1.5 x 10 to the 9th power/L (band neutrophil and segmented neutrophil), platelets \> 100 x 10 to the 9th power/L and Hb≥90g/L.

   Hepatic: total bilirubin less than or equal to 1.5 times upper limit of normal (ULN).

   Alkaline phosphatase (AP), alanine transaminase (ALT) and aspartate transaminase (AST) less than or equal to 3.0 times ULN (or less than or equal to 5 times ULN in case of known liver involvement.

   Renal: Serum Creatinine less than or equal to 1.25 times upper limit of normal (ULN).
8. Females of child-bearing potential must have negative serum pregnancy test. Sexually active males and females (of childbearing potential) willing to practice contraception during the study.

Exclusion Criteria:

1. Do not meet the above criteria.
2. Unhealed toxicity of prior anti-cancer treatment (CTCAE Level 1) or surgery.
3. Symptomatic Central Nervous System (CNS) metastases.
4. Clinical uncontrolled active infection, such as acute pneumonia, active hepatitis B or C (prior hepatitis B history, despite medication treatment control or not, HBV DNA≥500copies or ≥100IU/ml), etc.
5. Prior other malignant disease in 5 years (except carcinoma in situ of cervix, or non melanoma skin cancers, or localized prostate cancer with Gleason ≤6).
6. Take part in new drug clinical trials within one month or taking part in a trial now.
7. Pregnant or lactating woman.
8. Other conditions regimented at investigators' discretion.

Primary outcomes:
measure: PFS ratio in 12 week
timeFrame: 12 week
Secondary outcomes:
measure: OR Rate
timeFrame: 12 week
Other outcomes:
Locations:
Study officials:
affiliation: Director of Department of Medical Oncology,The First Hospital of China Medical University Affiliation: China Medical University, China
name: Liu yunpeng, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Xu XW, Yuan ZZ, Hu WH, Wang XK. [Meta-analysis on elemene injection combined with cisplatin chemotherapeutics in treatment of non-small cell lung cancer]. Zhongguo Zhong Yao Za Zhi. 2013 May;38(9):1430-7. Chinese.
citation: Li QQ, Wang G, Huang F, Li JM, Cuff CF, Reed E. Sensitization of lung cancer cells to cisplatin by beta-elemene is mediated through blockade of cell cycle progression: antitumor efficacies of beta-elemene and its synthetic analogs. Med Oncol. 2013 Mar;30(1):488. doi: 10.1007/s12032-013-0488-9. Epub 2013 Feb 9.
citation: Liu J, Hu XJ, Jin B, Qu XJ, Hou KZ, Liu YP. beta-Elemene induces apoptosis as well as protective autophagy in human non-small-cell lung cancer A549 cells. J Pharm Pharmacol. 2012 Jan;64(1):146-53. doi: 10.1111/j.2042-7158.2011.01371.x. Epub 2011 Oct 27.
citation: Matsuoka H, Kaneda H, Sakai K, Koyama A, Nishio K, Nakagawa K. Clinical Response to Everolimus of EGFR-Mutation-Positive NSCLC With Primary Resistance to EGFR TKIs. Clin Lung Cancer. 2017 Jan;18(1):e85-e87. doi: 10.1016/j.cllc.2016.08.004. Epub 2016 Oct 4. No abstract available.
citation: Passiglia F, Listi A, Castiglia M, Perez A, Rizzo S, Bazan V, Russo A. EGFR inhibition in NSCLC: New findings.... and opened questions? Crit Rev Oncol Hematol. 2017 Apr;112:126-135. doi: 10.1016/j.critrevonc.2017.02.009. Epub 2017 Feb 16.