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

Overview[ - collapse ][ - ]

Purpose 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
ConditionMultiple Brain Metastases
Non-small-cell Lung Cancer
InterventionDrug: Erlotinib
Drug: WBRT
PhasePhase 3
SponsorDaping Hospital and the Research Institute of Surgery of the Third Military Medical University
Responsible PartyDaping Hospital and the Research Institute of Surgery of the Third Military Medical University
ClinicalTrials.gov IdentifierNCT01887795
First ReceivedJune 8, 2013
Last UpdatedApril 20, 2014
Last verifiedApril 2014

Tracking Information[ + expand ][ + ]

First Received DateJune 8, 2013
Last Updated DateApril 20, 2014
Start DateAugust 2013
Estimated Primary Completion DateAugust 2016
Current Primary Outcome MeasuresTime to neurologic progression [Time Frame: 13 months] [Designated as safety issue: Yes]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)
Current Secondary Outcome Measures
  • Overall Survival [Time Frame: 3 years] [Designated as safety issue: Yes]
  • Complete response, Partial response, Stable disease, Progressive disease [Time Frame: 19 months] [Designated as safety issue: Yes]
  • Quality of Life [Time Frame: 3 years] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief TitlePhase 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
Official TitleNot Provided
Brief 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
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 TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Multiple Brain Metastases
  • Non-small-cell Lung Cancer
InterventionDrug: Erlotinib
Drug: WBRT
Study Arm (s)
  • Experimental: 1. WBRT alone
    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
  • Experimental: 2. Erlotinib concurrent WBRT
    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

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment224
Estimated Completion DateAugust 2016
Estimated Primary Completion DateAugust 2016
Eligibility Criteria
Inclusion Criteria:

1. 18 years of age or older;

2. the pathological diagnosis of non-small cell lung cancer and detection of pulmonary
primary ARMs / sequencing EGFR mutation;

3. enhanced MRI showed brain metastases ≥ 2 or NSCLC of brain metastases after resection
of residual lesions in ≥ 2 / intracranial metastases in patients with new;

4. if the previous use of EGFR-TKIs, in an WBRT synchronous Erotinib before treatment to
disable EGFR-TKIs ≥ 4 weeks;

5. expected survival period over 2 months;

6. KPS score ≥ 70;

7. GPA score 0.5 - 3.5;

8. a week before randomization, bone marrow and liver and kidney function in patients
with meet the following criteria:

1. HB ≥ 100, g/L ≥ 1.5 × 109/L neutrophil and platelet ≥ 100 × 109/L;

2. 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;

3. more than 1.5 times the upper limit of normal serum creatinine or creatinine
clearance rate ≥ 60 ml/min, urea N ≤ 200mg/L;

4. Urine dipstick testing the proteinuria < 1+; if the urine dipstick test value,
1+, is 24 hours total urine protein must < 500mg.

9. compliance research plan and follow-up process, and be able to carry out oral
therapy;

10. 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;

11. can understand and consent.

Exclusion Criteria:

1. patients have been treated with radiation to the brain or to erlotinib and its
ingredients allergies;

2. mixed with small cell lung cancer patients with components;

3. 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);

4. before entering the group 4 weeks received any other investigational drugs;

5. 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;

6. 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;

7. on gastrointestinal physiology is not perfect, or absorb the obstacle syndrome, or
unable to tolerate oral medication, or active peptic ulcer;

8. 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;

9. without full control of ocular inflammation or eye infections, or any may cause the
eye disease situation;

10. known human immunodeficiency virus (HIV) infection;

11. with immunodeficiency disease, or suffer from other acquired, congenital
immunodeficiency disease, or a history of organ transplantation;

12. any disease, metabolic disorders, or physical examination or laboratory suspicion or
treatment of complications in patients at high risk of drug.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsContact: Zhenzhou Yang
yangzz1970@163.com
Location CountriesChina

Administrative Information[ + expand ][ + ]

NCT Number NCT01887795
Other Study ID NumbersYang-1970
Has Data Monitoring CommitteeYes
Information Provided ByDaping Hospital and the Research Institute of Surgery of the Third Military Medical University
Study SponsorDaping Hospital and the Research Institute of Surgery of the Third Military Medical University
CollaboratorsNot Provided
Investigators Not Provided
Verification DateApril 2014

Locations[ + expand ][ + ]

Zhenzhou-Yang
Chongqing, Chongqing, China
Contact: Zhenzhou Yang, PHD | yangzz1970@163.com
Recruiting