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

Sponsor
Fujian Cancer Hospital (Other)
Overall Status
Unknown status
CT.gov ID
NCT03486496
Collaborator
(none)
50
Enrollment
1
Location
1
Arm
19.9
Anticipated Duration (Months)
2.5
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Jun 5, 2018
Anticipated Primary Completion Date :
Jun 1, 2019
Anticipated Study Completion Date :
Feb 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Gefitinib and Berberine

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

Drug: gefitinib
Patients will be treated with gefitinib, 250 mg p.o., daily
Other Names:
  • Iressa (AstraZeneca)

    • Drug: Berberine
    Patients will be treated with Berberine, 50 mg p.o., tid
    Other Names:
  • Berberine Sulfate

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression free survival [Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient]

      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

    1. Objective response [through study completion,an average of three years]

      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.

    2. safety [Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient]

      Adverse events graded according to NCI CTCAE V4.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Fujian cancer hospital Fuzhou Fujian China

    Sponsors and Collaborators

    • Fujian Cancer Hospital

    Investigators

    • Principal Investigator: Cheng Huang, MD., Fujian Cancer Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Fujian Cancer Hospital
    ClinicalTrials.gov Identifier:
    NCT03486496
    Other Study ID Numbers:
    • CSWOF201801
    First Posted:
    Apr 3, 2018
    Last Update Posted:
    Apr 3, 2018
    Last Verified:
    Mar 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Fujian Cancer Hospital
    Lung Adenocarcinoma
    EGFR mutation
    Gefitinib
    Berberine
    Additional relevant MeSH terms:
    Adenocarcinoma
    Adenocarcinoma of Lung
    Gefitinib

    Study Results

    No Results Posted as of Apr 3, 2018