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.
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
Drug | Synonyms | Arms |
---|
gefitinib | Iressa (AstraZeneca) | Gefitinib and Berberine |
Berberine | Berberine Sulfate | Gefitinib 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
Name | Type | Description | Interventions |
---|
Gefitinib and Berberine | Experimental | Experimental: Gefitinib and Berberine Patients will be treated with Gefitinib and Berberine. Gefitinib: 250 mg p.o., daily. Berberine: 50 mg p.o., tid. | |
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: | Unknown status |
Lead Sponsor: | Fujian Cancer Hospital |
Trial Keywords
- Lung Adenocarcinoma
- EGFR mutation
- Gefitinib
- Berberine
Last Updated
April 3, 2018