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

Primary Purpose

Non Small Cell Lung Cancer

Status

Unknown status

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

β-elemene

EGFR-TKIs(Erlotinib, Gefitinib and Icotinib)

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring beta-elemene

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Obtain of informed consent.
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.
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).
Eastern Cooperative Oncology Group（ECOG）Performance Status（PS） :0-2.
Aged from 18 to 75 years (18 and 75 years are included).
Life expectancy ≥12 weeks.
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).
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:

Do not meet the above criteria.
Unhealed toxicity of prior anti-cancer treatment (CTCAE Level 1) or surgery.
Symptomatic Central Nervous System (CNS) metastases.
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.
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).
Take part in new drug clinical trials within one month or taking part in a trial now.
Pregnant or lactating woman.
Other conditions regimented at investigators' discretion.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

β-elemene+EGFR TKI

EGFR TKI

Arm Description

EGFR-TKIs(Erlotinib, Gefitinib and Icotinib) and β-elemene

EGFR-TKIs(Erlotinib, Gefitinib and Icotinib)

Outcomes

Primary Outcome Measures

PFS ratio in 12 week

progression free survival ratio in 12 week

Secondary Outcome Measures

OR Rate

Objective Response Rate

Full Information

NCT ID

NCT03123484

First Posted

April 5, 2017

Last Updated

April 18, 2017

Sponsor

China Medical University, China

Collaborators

The First Affiliated Hospital of Dalian Medical University, The Second Affiliated Hospital of Dalian Medical University, Liaoning Tumor Hospital & Institute, Shengjing Hospital, General Hospital of Shenyang Military Region

1. Study Identification

Unique Protocol Identification Number

NCT03123484

Brief Title

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

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Unknown status

Study Start Date

April 2017 (Anticipated)

Primary Completion Date

April 2019 (Anticipated)

Study Completion Date

October 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

China Medical University, China

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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）

6. Conditions and Keywords

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

Non Small Cell Lung Cancer

Keywords

beta-elemene

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

β-elemene+EGFR TKI

Arm Type

Experimental

Arm Description

EGFR-TKIs(Erlotinib, Gefitinib and Icotinib) and β-elemene

Arm Title

EGFR TKI

Arm Type

Active Comparator

Arm Description

EGFR-TKIs(Erlotinib, Gefitinib and Icotinib)

Intervention Type

Drug

Intervention Name(s)

β-elemene

Other Intervention Name(s)

elemene liposomes

Intervention Description

β-elemene：400-600mg + 5%GS 500ml,ivgtt,qd, continuously 45days

Intervention Type

Drug

Intervention Name(s)

EGFR-TKIs(Erlotinib, Gefitinib and Icotinib)

Intervention Description

EGFR-TKIs(Erlotinib, Gefitinib and Icotinib) as usual

Primary Outcome Measure Information:

Title

PFS ratio in 12 week

Description

progression free survival ratio in 12 week

Time Frame

12 week

Secondary Outcome Measure Information:

Title

OR Rate

Description

Objective Response Rate

Time Frame

12 week

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Obtain of informed consent. 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. 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). Eastern Cooperative Oncology Group（ECOG）Performance Status（PS） :0-2. Aged from 18 to 75 years (18 and 75 years are included). Life expectancy ≥12 weeks. 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). 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: Do not meet the above criteria. Unhealed toxicity of prior anti-cancer treatment (CTCAE Level 1) or surgery. Symptomatic Central Nervous System (CNS) metastases. 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. 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). Take part in new drug clinical trials within one month or taking part in a trial now. Pregnant or lactating woman. Other conditions regimented at investigators' discretion.

Central Contact Person:

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

Liu yunpeng, PhD

Phone

86 24 83282312

cmu_trial@126.com

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

jin bo, PhD

Phone

86 24 83282542

jb_cmu@126.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Liu yunpeng, PhD

Organizational Affiliation

Director of Department of Medical Oncology,The First Hospital of China Medical University Affiliation: China Medical University, China

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

23944083

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.

Results Reference

background

PubMed Identifier

23397083

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.

Results Reference

background

PubMed Identifier

22150682

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.

Results Reference

background

PubMed Identifier

28341110

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.

Results Reference

background

PubMed Identifier

28325254

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.

Results Reference

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

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