Multiple Brain MetastasesPhase 3NCT01887795
Phase Ⅲ Trial of WBRT Versus Erlotinib Concurrent Whole-brain Radiation Therapy as first-line Treatment for Patients With Multiple Brain Metastases From Non-small-cell Lung Cancer(ENTER): a Multicentre, Open-label, Randomised Study
A Phase 3 study testing Erlotinib and WBRT in people with Multiple Brain Metastases and Non-small-cell Lung Cancer, run by Daping Hospital and the Research Institute of Surgery of the Third Military Medical University at 1 site in China.
Trial summary
1. Verify the effect of Erlotinib concurrent whole-brain radiation therapy as first-line treatment for patients with multiple brain metastases from non-small-cell lung cancer to compare with WBRT alone. 2. Verify pre-built EGFR mutation prediction model for NSCLC brain metastases Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multiple Brain Metastases, Non-small-cell Lung Cancer
- What is being tested?
- Erlotinib and WBRT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- 1 siteChina
- Study dates
- Aug 2013to Aug 2016
- Phase
- Phase 3
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18 years of age or older;
- the pathological diagnosis of non-small cell lung cancer and detection of pulmonary primary ARMs / sequencing EGFR mutation;
- enhanced MRI showed brain metastases ≥ 2 or NSCLC of brain metastases after resection of residual lesions in ≥ 2 / intracranial metastases in patients with new;
- if the previous use of EGFR-TKIs, in an WBRT synchronous Erotinib before treatment to disable EGFR-TKIs ≥ 4 weeks;
- expected survival period over 2 months;
- KPS score ≥ 70;
Show all 15Show fewer
- GPA score 0.5 - 3.5;
- a week before randomization, bone marrow and liver and kidney function in patients with meet the following criteria:
- HB ≥ 100, g/L ≥ 1.5 × 109/L neutrophil and platelet ≥ 100 × 109/L;
- total bilirubin ≤ 1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 times the upper limit of normal;
- more than 1.5 times the upper limit of normal serum creatinine or creatinine clearance rate ≥ 60 ml/min, urea N ≤ 200mg/L;
- Urine dipstick testing the proteinuria < 1+; if the urine dipstick test value, 1+, is 24 hours total urine protein must < 500mg.
- compliance research plan and follow-up process, and be able to carry out oral therapy;
- in women of childbearing age, must be in before starting treatment within 7 day of urine pregnancy test and the result is negative, and not in the lactation period, and reproductive age men and women prior to entry into the study, the research process until 90 days after stopping all agree to use reliable methods of contraception;
- can understand and consent.
Who cannot join
- patients have been treated with radiation to the brain or to erlotinib and its ingredients allergies;
- mixed with small cell lung cancer patients with components;
- 5 years before other cancers except NSCLC treatment in patients with the start of the study (except for simple operation resection and there are at least 5 consecutive years disease free survival, has been cured of cervical carcinoma in situ, has cured the base cell cancer and bladder epithelial tumor);
- before entering the group 4 weeks received any other investigational drugs;
- judgment according to the researchers, there are serious harm to patient safety or affect the patients completed the study with the disease, and patient compliance with the difference;
- had any clinical evidence of moderate to severe chronic obstructive pulmonary disease (COPD -COPD a history or risk factors of pulmonary function testing, FEV1/FVC<70%, FEV1<80% estimates, with or without chronic cough, sputum, difficulty breathing), activity of interstitial lung disease (-ILD pulmonary function test FEV1/FVC<70%, FEV1<80% estimates, dispersion carbon monoxide lung volume -DLCO<40%, high resolution CT showed a diffuse interstitial lung disease) disease activity and other researchers decided;
Show all 12Show fewer
- on gastrointestinal physiology is not perfect, or absorb the obstacle syndrome, or unable to tolerate oral medication, or active peptic ulcer;
- any unstable system diseases: including active infection, uncontrolled hypertension, unstable angina pectoris, within the last 3 months of the onset of angina, congestive heart failure, the group in June before the myocardial infarction, need serious mental disorder drug treatment, liver, kidney or metabolic diseases; mental / spiritual diseases such as Alzheimer's disease;
- without full control of ocular inflammation or eye infections, or any may cause the eye disease situation;
- known human immunodeficiency virus (HIV) infection;
- with immunodeficiency disease, or suffer from other acquired, congenital immunodeficiency disease, or a history of organ transplantation;
- any disease, metabolic disorders, or physical examination or laboratory suspicion or treatment of complications in patients at high risk of drug.
Trial locations and contacts
1 site in 1 country.
About this study
- Verify the effect of Erlotinib concurrent whole-brain radiation therapy as first-line treatment for patients with multiple brain metastases from non-small-cell lung cancer to compare with WBRT alone.
- Verify pre-built EGFR mutation prediction model for NSCLC brain metastases
Read the detailed description
All patients will be randomized to receive WBRT or Erlotinib concurrent WBRT. Erlotinib concurrent WBRT, patients were given a loading dose of erlotinib 150mg per day for 6 days, after which all patients received erlotinib 150mg per day concurrently with WBRT. Dose reduction was allowed for intolerable adverse effects (grade ≥3) such as rash or diarrhea in 50 mg increments down from 150mg to 100 mg and then to 50 mg if needed. Radiation therapy was delivered in 2.0 Gy fractions once per day 5 days per week to a total dose of 40Gy (20 fractions). Radiation was delivered as opposed lateral 8-MV beams with a Sweden precise linear accelerator.
- Being tested
- Erlotinib, WBRT
- Keywords
- Informed Consent;, Ethical Principles;, Data collection
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErlotinibDrug
WBRTDrug
| Study group | Role | What they receive |
|---|---|---|
| 1. WBRT alone | Experimental | Selected 224 patients with multiple brain metastases from NSCLC, they will be randomized to WBRT or Erotinib concurrent WBRT. It was enough to compare the efficacy of Erotinib concurrent WBRT vs. WBRT Receives: Drug: WBRT |
| 2. Erlotinib concurrent WBRT | Experimental | Selected 224 patients with multiple brain metastases from NSCLC, they will be randomized to WBRT or Erotinib concurrent WBRT. It was enough to compare the efficacy of Erotinib concurrent WBRT vs. WBRT Receives: Drug: Erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to neurologic progression
- assess the local control of brain metastases status (including: the proportion of salvage therapy, the proportion of radiation necrosis lesions)
- evaluation of intracranial metastasis status (at the site of the primary tumor than the emergence of new brain metastases)
Measured: 13 months
Secondary outcomes (3)
Overall Survival
Measured: 3 years
Complete response, Partial response, Stable disease, Progressive disease
Measured: 19 months
Quality of Life
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2013 (estimated)
- Study startAug 2013
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple Brain MetastasesStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 224 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhen-zhou Yang, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01887795
- Sponsor's protocol ID
- Yang-1970
- Status last verified
- Aug 2016
- First submitted
- 8 Jun 2013
- Last updated
- 25 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tang F, Zhang J, Xu Z, Zhang Y, Zhang X, Peng Y, Yang Z. Health-related quality of life analysis from ENTER, a randomized, controlled phase III trial of whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases. Transl Lung Cancer Res. 2024 Dec 31;13(12):3289-3302. doi: 10.21037/tlcr-24-481. Epub 2024 Dec 27.
PubMed 39830774Yang Z, Zhang Y, Li R, Yisikandaer A, Ren B, Sun J, Li J, Chen L, Zhao R, Zhang J, Xia X, Liao Z, Carbone DP. Whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases: a multicenter, open-label, randomized, controlled phase III trial. Neuro Oncol. 2021 Jun 1;23(6):967-978. doi: 10.1093/neuonc/noaa281.
PubMed 33331923
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ⅲ Trial of WBRT Versus Erlotinib Concurrent Whole-brain Radiation Therapy as first-line Treatment for Patients With Multiple Brain Metastases From Non-small-cell Lung Cancer(ENTER): a Multicentre, Open-label, Randomised Study
- ClinicalTrials.gov ID
- NCT01887795
- Acronym / sponsor ID
- Yang-1970
- Keywords
- Informed Consent;, Ethical Principles;, Data collection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 224 participants (actual)
- Lead sponsor
- Daping Hospital and the Research Institute of Surgery of the Third Military Medical UniversityUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 27 Jun 2013 (estimated)
- 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.
- Verify the effect of Erlotinib concurrent whole-brain radiation therapy as first-line treatment for patients with multiple brain metastases from non-small-cell lung cancer to compare with WBRT alone.
- Verify pre-built EGFR mutation prediction model for NSCLC brain metastases
Detailed description
All patients will be randomized to receive WBRT or Erlotinib concurrent WBRT. Erlotinib concurrent WBRT, patients were given a loading dose of erlotinib 150mg per day for 6 days, after which all patients received erlotinib 150mg per day concurrently with WBRT. Dose reduction was allowed for intolerable adverse effects (grade ≥3) such as rash or diarrhea in 50 mg increments down from 150mg to 100 mg and then to 50 mg if needed. Radiation therapy was delivered in 2.0 Gy fractions once per day 5 days per week to a total dose of 40Gy (20 fractions). Radiation was delivered as opposed lateral 8-MV beams with a Sweden precise linear accelerator.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1. WBRT alone | Experimental | Drug: WBRTSelected 224 patients with multiple brain metastases from NSCLC, they will be randomized to WBRT or Erotinib concurrent WBRT. It was enough to compare the efficacy of Erotinib concurrent WBRT vs. WBRT |
| 2. Erlotinib concurrent WBRT | Experimental | Drug: ErlotinibSelected 224 patients with multiple brain metastases from NSCLC, they will be randomized to WBRT or Erotinib concurrent WBRT. It was enough to compare the efficacy of Erotinib concurrent WBRT vs. WBRT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 18 years of age or older;
- the pathological diagnosis of non-small cell lung cancer and detection of pulmonary primary ARMs / sequencing EGFR mutation;
- enhanced MRI showed brain metastases ≥ 2 or NSCLC of brain metastases after resection of residual lesions in ≥ 2 / intracranial metastases in patients with new;
- if the previous use of EGFR-TKIs, in an WBRT synchronous Erotinib before treatment to disable EGFR-TKIs ≥ 4 weeks;
- expected survival period over 2 months;
Key exclusion criteria (12 listed)
- patients have been treated with radiation to the brain or to erlotinib and its ingredients allergies;
- mixed with small cell lung cancer patients with components;
- 5 years before other cancers except NSCLC treatment in patients with the start of the study (except for simple operation resection and there are at least 5 consecutive years disease free survival, has been cured of cervical carcinoma in situ, has cured the base cell cancer and bladder epithelial tumor);
- before entering the group 4 weeks received any other investigational drugs;
- judgment according to the researchers, there are serious harm to patient safety or affect the patients completed the study with the disease, and patient compliance with the difference;
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 |
|---|---|---|
| Erlotinib | Drug | 2. Erlotinib concurrent WBRT |
| WBRT | Drug | 1. WBRT alone |
Primary outcome
Time to neurologic progression
Time frame: 13 months
A) assess the local control of brain metastases status (including: the proportion of salvage therapy, the proportion of radiation necrosis lesions) B) evaluation of intracranial metastasis status (at the site of the primary tumor than the emergence of new brain metastases)
3 secondary outcomes
Overall Survival
Time frame: 3 years
Complete response, Partial response, Stable disease, Progressive disease
Time frame: 19 months
Quality of Life
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2016.
- Derived from this study: PubMed 39830774Tang F, Zhang J, Xu Z, Zhang Y, Zhang X, Peng Y, Yang Z. Health-related quality of life analysis from ENTER, a randomized, controlled phase III trial of whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases. Transl Lung Cancer Res. 2024 Dec 31;13(12):3289-3302. doi: 10.21037/tlcr-24-481. Epub 2024 Dec 27.
- Derived from this study: PubMed 33331923Yang Z, Zhang Y, Li R, Yisikandaer A, Ren B, Sun J, Li J, Chen L, Zhao R, Zhang J, Xia X, Liao Z, Carbone DP. Whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases: a multicenter, open-label, randomized, controlled phase III trial. Neuro Oncol. 2021 Jun 1;23(6):967-978. doi: 10.1093/neuonc/noaa281.
Related trials for Multiple Brain Metastases
RecruitingPhase 3
FSRT Combines With Bevacizumab for Multiple Brain Metastases in Lung Adenocarcinoma
Multiple Brain Metastases in Lung Adenocarcinoma
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Erlotinib and WBRT in people with Multiple Brain Metastases and Non-small-cell Lung Cancer, run by Daping Hospital and the Research Institute of Surgery of the Third Military Medical University 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 15 inclusion and 12 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: finished, as of the sponsor's last update on 25 Aug 2016. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to neurologic progression (time frame: 13 months). 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 NCT01887795, which also lists 2 linked publications.
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 25 Aug 2016; AzTrials last refreshed its copy on 8 Nov 2026.