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

Multicenter Phase III Study of Gefitinib Mono-therapy or Gefitinib Combined With Chemotherapy in Patients With Brain Metastases From Non-small Cell Lung Cancer Harboring EGFR Mutation

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.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer; Brain Metastases; EGFR Mutation
• Intervention / Treatment: Drug: Gefitinib and Pemetrexed/platinum; Drug: Gefitinib mono-therapy

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: li-kun Chen, MD; Phone Number: 13798019964; Email: chenlk@sysucc.org.cn
• Study Contact Backup: Name: Xue Hou; Phone Number: 13570569436; Email: houxue@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University of Cancer Center
      • Contact: li-kun Chen, doctor; Phone Number: 13798019964; Email: chenlk@sysucc.org.cn
      • Principal Investigator: li-kun Chen, doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gefitinib and Pemetrexed/platinum; 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	Drug: Gefitinib and Pemetrexed/platinum; Gefitinib 250mg is Taken Orally on day 1-28,combined Pemetrexed (D1)+cisplatin (D1-3) or Pemetrexed (D1) + nedaplatin (D1) chemotherapy, every 28 days
Active Comparator: Gefitinib mono-therapy; Gefitinib 250mg is Taken Orally everyday	Drug: Gefitinib mono-therapy; Gefitinib 250mg is Taken Orally everyday

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
iPFS(intracranial progression free survival	defined as time from randomization to intracranial progressive disease or death.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	proportion of patients with complete or partial response of overall lesions	2 years
intracranial objective response rate (iORR)	proportion of patients with complete or partial response of intracranial lesions	2 years
PFS(Progression Free Survival)	time from randomization to overall disease progression or death	2 years
OS(Overall Survival)	time from randomization to death from any cause	3 years
adverse events	adverse events were evaluated according to NCI-CTCAE 4.0.	3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Wu Jieping Medical Foundation

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: September 16, 2013
• First Submitted That Met QC Criteria: September 23, 2013
• First Posted (Estimate): September 26, 2013

Study Record Updates

• Last Update Posted (Actual): March 8, 2022
• Last Update Submitted That Met QC Criteria: February 19, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Gefitinib; Pemetrexed
• Other Study ID Numbers: NSCLC brain metastasis 01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No