Clinical Trials /

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

NCT03486496

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CSWOF201801
  • NCT ID: NCT03486496

Conditions

  • Lung Adenocarcinoma
  • EGFR Mutation

Interventions

DrugSynonymsArms
gefitinibIressa (AstraZeneca)Gefitinib and Berberine
BerberineBerberine SulfateGefitinib and Berberine

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Gefitinib and BerberineExperimentalExperimental: Gefitinib and Berberine Patients will be treated with Gefitinib and Berberine. Gefitinib: 250 mg p.o., daily. Berberine: 50 mg p.o., tid.
  • gefitinib
  • Berberine

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient
Safety Issue:
Description: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

Measure:Objective response
Time Frame:through study completion,an average of three years
Safety Issue:
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.
Measure:safety
Time Frame:Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient
Safety Issue:
Description:Adverse events graded according to NCI CTCAE V4.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Fujian Cancer Hospital

Trial Keywords

  • Lung Adenocarcinoma
  • EGFR mutation
  • Gefitinib
  • Berberine

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