Gefitinib With or Without Chemotherapy in Brain Metastases From Non-small Cell Lung Cancer

Sun Yat-sen University

Status and phase: Unknown; Phase 3

Conditions: Brain Metastases; EGFR Mutation; Non-small Cell Lung Cancer

Treatments: Drug: Gefitinib and Pemetrexed/platinum; Drug: Gefitinib mono-therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT01951469

NSCLC brain metastasis 01

Details and patient eligibility

About

This is a multi-center phase III randomized controlled study to assess the efficacy of Gefitinib alone and Gefitinib combination with Pemetrexed/platinum on patients with brain metastasis from non-small cell lung cancer(NSCLC) harboring EGFR mutation type by intracranial PFS(iPFS),also PFS ,DCR and OS.The side effect is evaluated as well.

Enrollment: 160 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patient who was confirmed stage IV NSCLC with EGFR activating mutation and brain metastases by pathologic histology or cytology
2. Patients who had never received therapy (including chemotherapy,WBRT,EGFR-TKI and EGFR monoclonal antibody) after diagnosed brain metastases
3. Patients had at least three metastatic lesions in brain, or patients with 1-2 intracranial lesions who were not suitable for brain radiotherapy, or patients with 1-2 intracranial lesions who refused brain radiotherapy, at least one intracranial lesion with the longest diameter of >5 mm
4. Adult patients (≥ 18 years and ≤75 years). ECOG Performance Status 0 or 1 Life expectancy of at least 12 weeks.,Haemoglobin ³ 10.0 g/dl, Absolute neutrophil count (ANC) ³1.5 x 109/L, platelets ³ 100 x 109/L. Total bilirubin £ 1.5 x upper limit of normal (ULN). ALT and AST < 2.5 x ULN in the absence of liver metastases, or < 5 x ULN in case of liver metastases. Creatinine clearance ³ 60ml/min (calculated according to Cockcroft-gault formula).
5. Patients should be contraceptive during the period of the trial until 8 weeks after the last administration of icotinib.
6. Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.

Exclusion criteria

1. Patient was received irradiation of brain. Patient with meningeal metastases were confirmed by MRI or cytology test of cerebrospinal fluid.
2. Patient is received the treatment of Phenytoin, carbamazepine, rifampicin, phenobarbital, or St. John's Wort.
3. Patient was received EGFR Tyrosine Kinase Inhibitor or EGFR monoclonal antibody.
4. Interstitial pneumonia.Pericardial effusion, pleural effusion is uncontrolled .
5. Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
6. Any significant ophthalmologic abnormality ,especially severe dry eye syndrome ,keratoconjunctivitis sicca,Sjogren syndrome,severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions.
7. Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or have active peptic ulcer disease.
8. The symptoms of increased intracranial pressure are uncontrolled after dehydration and cortisone treatment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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160 participants in 2 patient groups

Gefitinib and Pemetrexed/platinum

Experimental group

Description:

Gefitinib 250mg is Taken Orally on day 1-28,combined Pemetrexed (D1)+cisplatin (D1-3) chemotherapy or Pemetrexed (D1)+nedaplatin (D1) chemotherapy, every 28 days

Treatment:

Drug: Gefitinib and Pemetrexed/platinum

Gefitinib mono-therapy

Active Comparator group

Description:

Gefitinib 250mg is Taken Orally everyday

Treatment:

Drug: Gefitinib mono-therapy