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Gefitinib and Berberine in the First-line Treatment of Lung Adenocarcinoma With EGFR Mutation (Geber)

Primary Purpose

Lung Adenocarcinoma, EGFR Mutation

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

gefitinib

Berberine

About this trial

This is an interventional treatment trial for Lung Adenocarcinoma focused on measuring Lung Adenocarcinoma, EGFR mutation, Gefitinib, Berberine

Eligibility Criteria

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

Inclusion Criteria:

Age ≥ 18 years
ECOG performance status 0-2
Adequate haematological function, coagulation, liver function and renal function
Pathological diagnosis of predominantly non-squamous, non-small-cell lung cancer (NSCLC)
TNM version 7 stage IV disease including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease not amenable to curative treatment (including patients progressing after radiochemotherapy for stage III disease)
Measurable or evaluable disease (according to RECIST 1.1 criteria).
Centrally confirmed EGFR exon 19 deletion (del19) or exon 21 mutation (L858R)

Exclusion Criteria:

Patients who have had in the past 5 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ breast carcinoma.

Patients with any known significant ophthalmologic anomaly of the ocular surface

Patients who received prior chemotherapy for metastatic disease
Patients who received previous treatment for lung cancer with drugs targeting EGFR or VEGF
Pregnancy

Sites / Locations

Fujian cancer hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gefitinib and Berberine

Arm Description

Experimental: Gefitinib and Berberine Patients will be treated with Gefitinib and Berberine. Gefitinib: 250 mg p.o., daily. Berberine: 50 mg p.o., tid.

Outcomes

Primary Outcome Measures

Progression free survival

Time from the date of enrolment to discontinuation of treatment for any reason (including progression of disease, treatment toxicity, refusal and death)

Secondary Outcome Measures

Objective response

Best overall response (complete remission or partial remission) across all assessment time-points according to RECIST Criteria 1.1, during the period from enrolment to termination of trial treatment.

safety

Adverse events graded according to NCI CTCAE V4.

Full Information

NCT ID

NCT03486496

First Posted

March 24, 2018

Last Updated

March 31, 2018

Sponsor

Fujian Cancer Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03486496

Brief Title

Gefitinib and Berberine in the First-line Treatment of Lung Adenocarcinoma With EGFR Mutation

Acronym

Geber

Official Title

An Open-label Phase II Trial of Gefitinib and Berberine in Patients With Advanced Non-small Cell Lung Cancer and Activating EGFR Mutations

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Unknown status

Study Start Date

June 5, 2018 (Anticipated)

Primary Completion Date

June 1, 2019 (Anticipated)

Study Completion Date

February 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fujian Cancer Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Rationale: Advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations (del19 or L858R) show an impressive progression-free survival between 9 and 11 months when treated with gefitinib. Combination of gefitinib and berberine could improve efficacy in lung cancer with EGFR mutation in vivo and vitro. The investigators hypothesize that progression-free survival could be improved by combination of gefitinib and berberine.

Detailed Description

Strong lipogenic activity and high expression of sterol regulatory element-binding protein 1 (SREBP-1) were found in gefitinib-resistance NSCLC cells. Berberine, an effective suppressor of SREBP1 and lipogenesis regulated through ROS/AMPK pathway, selectively inhibited the growth of gefitinib-resistance NSCLC cells but not that of normal cells. It effectively caused mitochondrial dysfunction, activated reactive oxygen species (ROS)/AMPK pathway and finally suppressed cellular lipogenesis and cell proliferation. Addition of ROS blocker, AMPK inhibitor and palmitic acid significantly reduced the effect of Berberine. In in vivo study, treatment of Berberine led to significant inhibition of mouse tumor xenograft growth.

6. Conditions and Keywords

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

Lung Adenocarcinoma, EGFR Mutation

Keywords

Lung Adenocarcinoma, EGFR mutation, Gefitinib, Berberine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Gefitinib and Berberine

Arm Type

Experimental

Arm Description

Experimental: Gefitinib and Berberine Patients will be treated with Gefitinib and Berberine. Gefitinib: 250 mg p.o., daily. Berberine: 50 mg p.o., tid.

Intervention Type

Drug

Intervention Name(s)

gefitinib

Other Intervention Name(s)

Iressa (AstraZeneca)

Intervention Description

Patients will be treated with gefitinib, 250 mg p.o., daily

Intervention Type

Drug

Intervention Name(s)

Berberine

Other Intervention Name(s)

Berberine Sulfate

Intervention Description

Patients will be treated with Berberine, 50 mg p.o., tid

Primary Outcome Measure Information:

Title

Progression free survival

Description

Time from the date of enrolment to discontinuation of treatment for any reason (including progression of disease, treatment toxicity, refusal and death)

Time Frame

Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient

Secondary Outcome Measure Information:

Title

Objective response

Description

Best overall response (complete remission or partial remission) across all assessment time-points according to RECIST Criteria 1.1, during the period from enrolment to termination of trial treatment.

Time Frame

through study completion,an average of three years

Title

safety

Description

Adverse events graded according to NCI CTCAE V4.

Time Frame

Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥ 18 years ECOG performance status 0-2 Adequate haematological function, coagulation, liver function and renal function Pathological diagnosis of predominantly non-squamous, non-small-cell lung cancer (NSCLC) TNM version 7 stage IV disease including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease not amenable to curative treatment (including patients progressing after radiochemotherapy for stage III disease) Measurable or evaluable disease (according to RECIST 1.1 criteria). Centrally confirmed EGFR exon 19 deletion (del19) or exon 21 mutation (L858R) Exclusion Criteria: Patients who have had in the past 5 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ breast carcinoma. Patients with any known significant ophthalmologic anomaly of the ocular surface Patients who received prior chemotherapy for metastatic disease Patients who received previous treatment for lung cancer with drugs targeting EGFR or VEGF Pregnancy

Central Contact Person:

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

Gen Lin, Dr.

Phone

00861-591-83660063

lingen197505@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Cheng Huang, MD.

Organizational Affiliation

Fujian Cancer Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fujian cancer hospital

City

Fuzhou

State/Province

Fujian

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Individual participant data will be available

IPD Sharing Time Frame

Data will be available within 6 months of study completion

IPD Sharing Access Criteria

Data access requests will be reviewed by an external indepentent Review Panel. Requesdtors will be required to sign a Data Access Agreement.

Citations:

PubMed Identifier

28665143

Citation

Fan XX, Leung EL, Xie Y, Liu ZQ, Zheng YF, Yao XJ, Lu LL, Wu JL, He JX, Yuan ZW, Fu J, Wei CL, Huang J, Xiao DK, Luo LX, Jiang ZB, Zhou YL, Kam RK, Liu L. Suppression of Lipogenesis via Reactive Oxygen Species-AMPK Signaling for Treating Malignant and Proliferative Diseases. Antioxid Redox Signal. 2018 Feb 10;28(5):339-357. doi: 10.1089/ars.2017.7090. Epub 2017 Aug 4. Erratum In: Antioxid Redox Signal. 2019 Feb 1;30(4):710.

Results Reference

result

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Gefitinib and Berberine in the First-line Treatment of Lung Adenocarcinoma With EGFR Mutation

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