Non-Small Cell Lung CancerPhase 2/3EGFRNCT02338011
Comparator-Controlled Study for EGFR(+) Patients With Multiple BMs From NSCLC (BROKE) (EGFR-epidermal Growth Factor Receptor;BM-brain Metastases)
A Phase 2/3 study testing Gefitinib and WBRT in people with Non-Small Cell Lung Cancer and Brain Metastases, run by Shanghai Chest Hospital at 1 site in China.
Trial summary
1. Compare the effect and safety of gefitinib alone with gefitinib plus concomitant WBRT(whole-brain radiotherapy ) in treatment of NSCLC patients harboring an EGFR mutation with multiple BM. 2. Verify the failure pattern of NSCLC patients harboring an EGFR mutation with multiple BM. 3. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Non-Small Cell Lung Cancer, Brain Metastases, EGFR Gene Mutation
- What is being tested?
- Gefitinib and WBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 1 siteChina
- Study dates
- Nov 2014to Nov 2017
- Phase
- Phase 2/3
- 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
- years of age or older
- ECOG score ≤ 2
- Recursive Partitioning Analysis(RPA) Class I-II;
- The pathological diagnosis of primary non-small cell lung cancer and detection of pulmonary primary ARMs;
- Sequencing EGFR mutation(primary lesion or metastases,exon 19 deletions or exon 21 L858R (EGFR mutation in exon 21, L858R point mutation) mutations;
- Enhanced MRI showed brain metastases ≥ 4;
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- 1 or 2 line treatment revealed failure;
- No use of EGFR-TKIs(Tyrosine kinase inhibitors) previously；
- No treatment for BM previously,including WBRT、SRS、surgery or experimental therapy;
- Expected survival period over 3 months;
- Two weeks before randomization, organs function in patients with meet the following criteria:
- bone marrow:HB(hemoglobin) ≥ 90g/L, neutrophil≥ 1.5 × 109/L and platelet ≥ 100 × 109/L;
- liver function:total bilirubin ≤ 1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal;
- renal function:more than 1.5 times the upper limit of normal serum creatinine or creatinine clearance rate ≥ 60 ml/min;
- Urine dipstick testing the proteinuria < 1+; if the urine dipstick test value, 1+, is 24 hours total urine protein must < 500mg;
- blood glucose:normal range,DM(diabetes mellitus) patients are under treatment and have a stable state;
- Can understand and consent
Who cannot join
- Patients have been treated with brain radiation or surgery of BM;
- Prior of EGFR-TKIs；
- Mixed with small cell lung cancer patients with components;
- Wild-type of EGFR;
- Unable to tolerate MRI scanning;
- Post 2 line treated patients;
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- Brain meninges metastases or incorporate with brain meninges metastases;
- 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;
- Incorporate with local symptoms（hemiplegic paralysis、anepia、nystagmus、ataxia.et);
- Pregnancy or lactation female;
- Allergic to EGFR-TKIs or any components;
- Patients were not permitted to receive the following drugs: phenytoin, carbamazepine, rifampicin, phenobarbital or itraconazole because of their potential to affect the metabolism of EGFR-TKIs and reduce its plasma concentration. Patients were not permitted to receive oral medicine such as CoumadinTM、Warfarin. If anticoagulant therapy is needed,low molecular heparin is suggested to instead of Coumarin drugs;
- Organs function in patients with meet the following criteria:
- Diagnose with interstitial lung disease、drug induced interstitial disease、hormone dependent radiation pneumonia previously,et al;
- Any unstable system diseases: including active infection, moderate to severe chronic obstructive pulmonary disease, uncontrolled hypertension, unstable angina pectoris, congestive heart failure, within the last 6 months of the onset of myocardial infarction, need serious mental disorder drug treatment, liver, kidney or metabolic diseases; mental / spiritual diseases such as Alzheimer's disease;
- Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption or active peptic ulcer;
- With immunodeficiency disease, or suffer from other acquired, congenital immunodeficiency disease, or a history of organ transplantation;
- Known human immunodeficiency virus (HIV) infection;
- Without full control of ocular inflammation or eye infections, or any may cause the eye disease situation;
- 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.
China1 site, 1 recruiting
- Recruiting
Varian linear accelerato
Shanghai, Shanghai Municipality, 200030
Liyan Jiang, M.D,Ph.D, 18017321302, jiang_liyan2000@126.com
About this study
Official title: Gefitinib Alone or With Concomitant Whole Brain Radiotherapy for Patients Harboring an EGFR Mutation With Multiple Brain Metastases From Non-Small-cell Lung Cancer: a Phase II/III Randomized Controlled Trial
- Compare the effect and safety of gefitinib alone with gefitinib plus concomitant WBRT(whole-brain radiotherapy ) in treatment of NSCLC patients harboring an EGFR mutation with multiple BM.
- Verify the failure pattern of NSCLC patients harboring an EGFR mutation with multiple BM.
- Explore the rescuable therapy after progression of disease.
Read the detailed description
All patients will be randomized to receive gefitinib or gefitinib concurrent WBRT until progression of disease. Gefitinib concurrent WBRT, patients were given gefitinib 250mg per day concurrently with WBRT(whole-brain radiotherapy ). Dose reduction was allowed for intolerable adverse effects such as rash(grade 4)、diarrhea(grade 3-4) or non hematological toxicity(grade 3-4) from 250mg per day to 250mg every other day then to 250mg every three days if needed. WBRT was delivered in 3.0 Gy(Gray)fractions once per day 5 days per week to a total dose of 30Gy (10 fractions). Radiation was delivered as opposed lateral 6-MV(Micro Voltage) beams with Varian linear accelerator.
- Being tested
- Gefitinib, WBRT
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GefitinibDrug
Also called Iressa
Gefitinib was given 250mg per day. Dose reduction was allowed for intolerable adverse effects such as rash(grade 4)、diarrhea(grade 3-4) or non hematological toxicity(grade 3-4) from 250mg per day to 250mg every other day then to 250mg every three days if needed.
WBRTRadiation
WBRT was delivered in 3.0 Gy fractions once per day 5 days per week to a total dose of 30Gy (10 fractions).
| Study group | Role | What they receive |
|---|---|---|
| Gefitinib alone | Experimental | Patients harboring an EGFR mutation with multiple BM from NSCLC will receive Gefitinib 250mg per day until progression of disease. Receives: Drug: Gefitinib |
| Gefitinib concurrent WBRT | Experimental | Patients harboring an EGFR mutation with multiple BM from NSCLC will receive Gefitinib concurrent WBRT until progression of disease.Gefitinib was given 250mg per day. WBRT was delivered in 3.0 Gy fractions once per day 5 days per week to a total dose of 30Gy (10 fractions). Receives: Drug: Gefitinib; Radiation: WBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to progression
Compare the progression free survival(PFS) and safety in two arms,including intracranial PFS、extracranial PFS and overall PFS.
Measured: 12-14 months
Secondary outcomes (4)
Overall survival
Measured: 3 years
Disease Progression Classification
intracranial or extracranial site
Measured: 3 years
Health-related quality of life
measured by ECGO(Eastern Cooperative Oncology Group) PS (Performance Status)
Measured: 3 years
Mental Status
measured by scale of MMSE( Mini Mental Status Examination)
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 posted14 Jan 2015 (estimated)
- Study startNov 2014
- Primary completionNov 2017 (estimated)
- Study completionNov 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Chest Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Liyan Jiang, Shanghai Chest Hospital
- Investigators
- Liyan JIang, M.D,Ph.D., Study director, Department of Respiratory, Shanghai Chest Hospital,Shanghai JIaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02338011
- Sponsor's protocol ID
- ShanghaiChest Hospital
- Acronym
- EGFR
- Status last verified
- Jan 2015
- First submitted
- 23 Dec 2014
- Last updated
- 26 Jan 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gefitinib Alone or With Concomitant Whole Brain Radiotherapy for Patients Harboring an EGFR Mutation With Multiple Brain Metastases From Non-Small-cell Lung Cancer: a Phase II/III Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02338011
- Acronym / sponsor ID
- EGFR / ShanghaiChest Hospital
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- Shanghai Chest HospitalUniversity, hospital or other
- Study start
- Nov 2014
- Primary completion
- Nov 2017 (estimated)
- Study completion
- Nov 2017 (estimated)
- First posted
- 14 Jan 2015 (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.
- Compare the effect and safety of gefitinib alone with gefitinib plus concomitant WBRT(whole-brain radiotherapy ) in treatment of NSCLC patients harboring an EGFR mutation with multiple BM.
- Verify the failure pattern of NSCLC patients harboring an EGFR mutation with multiple BM.
- Explore the rescuable therapy after progression of disease.
Detailed description
All patients will be randomized to receive gefitinib or gefitinib concurrent WBRT until progression of disease. Gefitinib concurrent WBRT, patients were given gefitinib 250mg per day concurrently with WBRT(whole-brain radiotherapy ). Dose reduction was allowed for intolerable adverse effects such as rash(grade 4)、diarrhea(grade 3-4) or non hematological toxicity(grade 3-4) from 250mg per day to 250mg every other day then to 250mg every three days if needed. WBRT was delivered in 3.0 Gy(Gray)fractions once per day 5 days per week to a total dose of 30Gy (10 fractions). Radiation was delivered as opposed lateral 6-MV(Micro Voltage) beams with Varian linear accelerator.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gefitinib alone | Experimental | Drug: GefitinibPatients harboring an EGFR mutation with multiple BM from NSCLC will receive Gefitinib 250mg per day until progression of disease. |
| Gefitinib concurrent WBRT | Experimental | Drug: Gefitinib, Radiation: WBRTPatients harboring an EGFR mutation with multiple BM from NSCLC will receive Gefitinib concurrent WBRT until progression of disease.Gefitinib was given 250mg per day. WBRT was delivered in 3.0 Gy fractions once per day 5 days per week to a total dose of 30Gy (10 fractions). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- years of age or older
- ECOG score ≤ 2
- Recursive Partitioning Analysis(RPA) Class I-II;
- The pathological diagnosis of primary non-small cell lung cancer and detection of pulmonary primary ARMs;
- Sequencing EGFR mutation(primary lesion or metastases,exon 19 deletions or exon 21 L858R (EGFR mutation in exon 21, L858R point mutation) mutations;
Key exclusion criteria (21 listed)
- Patients have been treated with brain radiation or surgery of BM;
- Prior of EGFR-TKIs；
- Mixed with small cell lung cancer patients with components;
- Wild-type of EGFR;
- Unable to tolerate MRI scanning;
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: IressaGefitinib was given 250mg per day. Dose reduction was allowed for intolerable adverse effects such as rash(grade 4)、diarrhea(grade 3-4) or non hematological toxicity(grade 3-4) from 250mg per day to 250mg every other day then to 250mg every three days if needed. | Drug | Gefitinib alone, Gefitinib concurrent WBRT |
| WBRTWBRT was delivered in 3.0 Gy fractions once per day 5 days per week to a total dose of 30Gy (10 fractions). | Radiation | Gefitinib concurrent WBRT |
Primary outcome
Time to progression
Time frame: 12-14 months
Compare the progression free survival(PFS) and safety in two arms,including intracranial PFS、extracranial PFS and overall PFS.
4 secondary outcomes
Overall survival
Time frame: 3 years
Disease Progression Classification
Time frame: 3 years
Health-related quality of life
Time frame: 3 years
Mental Status
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2015.
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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.
Liyan JIang, M.D,Ph.D. study director
Department of Respiratory, Shanghai Chest Hospital,Shanghai JIaotong University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Gefitinib and WBRT in people with Non-Small Cell Lung Cancer and Brain Metastases, run by Shanghai Chest 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 17 inclusion and 21 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 26 Jan 2015. 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 combined 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.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Liyan JIang, M.D,Ph.D. (18017321302, liyanjiangxkyy@sina.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to progression (time frame: 12-14 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Jan 2015.