Lung AdenocarcinomaPhase 2GeberNCT03486496
Gefitinib and Berberine in the First-line Treatment of Lung Adenocarcinoma With EGFR Mutation
A Phase 2 study testing gefitinib and Berberine in people with Lung Adenocarcinoma and EGFR Mutation, run by Fujian Cancer Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Adenocarcinoma, EGFR Mutation
- What is being tested?
- gefitinib and Berberine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 5 Jun 2018to 1 Feb 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Lung Adenocarcinoma, EGFR Mutation
- Being tested
- gefitinib, Berberine
- Keywords
- Lung Adenocarcinoma, EGFR mutation, Gefitinib, Berberine
- Medical subject headings
- Adenocarcinoma of Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gefitinibDrug
Also called Iressa (AstraZeneca)
Patients will be treated with gefitinib, 250 mg p.o., daily
BerberineDrug
Also called Berberine Sulfate
Patients will be treated with Berberine, 50 mg p.o., tid
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: gefitinib; Drug: Berberine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient
Secondary outcomes (2)
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.
Measured: through study completion,an average of three years
safety
Adverse events graded according to NCI CTCAE V4.
Measured: Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2018
- Study start5 Jun 2018 (estimated)
- Primary completion1 Jun 2019 (estimated)
- Study completion1 Feb 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Fujian Cancer HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fujian Cancer Hospital
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Cheng Huang, MD., Principal investigator, Fujian Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03486496
- Sponsor's protocol ID
- CSWOF201801
- Acronym
- Geber
- Status last verified
- Mar 2018
- First submitted
- 24 Mar 2018
- Last updated
- 3 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data will be available
Publications
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.
PubMed 28665143
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03486496
- Acronym / sponsor ID
- Geber / CSWOF201801
- Conditions
- Lung Adenocarcinoma, EGFR Mutation
- Keywords
- Lung Adenocarcinoma, EGFR mutation, Gefitinib, Berberine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Fujian Cancer HospitalOther government
- Study start
- 5 Jun 2018 (estimated)
- Primary completion
- 1 Jun 2019 (estimated)
- Study completion
- 1 Feb 2020 (estimated)
- First posted
- 3 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gefitinib and Berberine | Experimental | Drug: gefitinib, Drug: BerberineExperimental: Gefitinib and Berberine Patients will be treated with Gefitinib and Berberine. Gefitinib: 250 mg p.o., daily. Berberine: 50 mg p.o., tid. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gefitinibAlso: Iressa (AstraZeneca)Patients will be treated with gefitinib, 250 mg p.o., daily | Drug | Gefitinib and Berberine |
| BerberineAlso: Berberine SulfatePatients will be treated with Berberine, 50 mg p.o., tid | Drug | Gefitinib and Berberine |
Primary outcome
Progression free survival
Time frame: 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)
2 secondary outcomes
Objective response
Time frame: through study completion,an average of three years
safety
Time frame: Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2018.
- Results publication: PubMed 28665143Fan 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.
- Individual participant dataSharing planned: Yes. Individual participant data will be available
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cheng Huang, MD. principal investigator
Fujian Cancer Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing gefitinib and Berberine in people with Lung Adenocarcinoma and EGFR Mutation, run by Fujian Cancer Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gen Lin, Dr. (00861-591-83660063, lingen197505@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: Within 6 months of the last visit of last patient, approximately 30 months after inclusion of first patient). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03486496, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2018.