β-elemene Combine With EGFR-TKI for Advanced EGFR-TKI-resistant NSCLC

Phase 2

• Conditions: Non Small Cell Lung Cancer
• Interventions: Drug: EGFR-TKIs(Erlotinib, Gefitinib and Icotinib); Drug: β-elemene

• Registration Number: NCT03123484
• Lead Sponsor: China Medical University, China

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）

Study Timeline

• Status Verified: 2017-04
• Study Start: 2017-04
• Study First Submitted: 2017-04-05
• Study First Submitted QC: 2017-04-18
• Last Update Submitted: 2017-04-18
• Study First Posted: 2017-04-21
• Last Update Posted: 2017-04-21
• Primary Completion: 2019-04
• Study Completion: 2019-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EGFR TKI	EGFR-TKIs(Erlotinib, Gefitinib and Icotinib)	EGFR-TKIs(Erlotinib, Gefitinib and Icotinib)
β-elemene+EGFR TKI	β-elemene	EGFR-TKIs(Erlotinib, Gefitinib and Icotinib) and β-elemene
β-elemene+EGFR TKI	EGFR-TKIs(Erlotinib, Gefitinib and Icotinib)	EGFR-TKIs(Erlotinib, Gefitinib and Icotinib) and β-elemene

Primary Outcome Measures

Name	Time	Method
PFS ratio in 12 week	12 week	progression free survival ratio in 12 week

Secondary Outcome Measures

Name	Time	Method
OR Rate	12 week	Objective Response Rate