Icotinib Combined With WBRT For NSCLC Patients With Brain Metastases and EGFR Mutation

A Single Center, Open Label, Dose-Finding Study to Determine the Safety of Icotinib in Combination With Whole Brain Radiation Therapy For NSCLC Patients With Brain Metastases and EGFR Mutation.

The purpose of this study is to evaluate the safety and tolerability of Icotinib at different dose levels in combination with whole brain radiotherapy for NSCLC patients with brain metastases and EGFR mutation.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer; Brain Metastases
• Intervention / Treatment: Drug: icotinib; Radiation: Whole brain radiotherapy

Detailed Description

The long-term control of brain metastases becomes a clinical challenge. Whole brain radiotherapy, the standard treatment for patients with multiple brain metastases, can only bring a modest survival improvement around 3-6 months. EGFR-TKIs like icotinib with its proven activity in non-small cell lung cancer may provide clinical benefits in such patients.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital

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:

• Histological or cytological confirmation of non-small cell lung cancer (NSCLC).
• Diagnosis of brain metastases on a Gadolinium-enhanced MRI. More than 3 sites of intracranial metastases, or the longest diameter of the intracranial lesion is more than 3cm.
• Positive EGFR mutation.

Exclusion Criteria:

• Previous usage of EGFR-TKI or antibody to EGFR: gefitinib, erlotinib, herceptin, erbitux.
• CSF or MRI findings consistent with metastases of spinal cord, meninges or meningeal.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Icotinib+WBRT; Standard whole brain radiotherapy plus icotinib, which is designed to administered at 5 dose according to "3+3" until disease progression or intolerable toxicity.

Drug: icotinib; Level 1: Standard whole brain radiation therapy plus icotinib 125 mg Tid (375 mg per day) from day1 until disease progression or intolerable toxicity. Level 2: Standard whole brain radiation therapy plus icotinib 250 mg Tid (750 mg per day) from day1 until disease progression or intolerable toxicity. Level 3: Standard whole brain radiation therapy plus icotinib 375 mg Tid (1125 mg per day) from day1 until disease progression or intolerable toxicity. Level 4:Standard whole brain radiation therapy plus icotinib 500 mg Tid (1500 mg per day) from day1 until disease progression or intolerable toxicity.; Other Names: BPI-2009, Conmana; Radiation: Whole brain radiotherapy; Whole Brain Radiation Therapy (WBRT) for total dose of 37.5Gy in 15 daily fractions beginning after Day 7.; Other Names: Radiotherapy; RT; XRT; WBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	All cause adverse events (AEs) and serious adverse events (SAEs)	6-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological progression-free survival	All cause neurological progress or mortality	3-6 month
Progression-free survival	All cause progress or mortality	3-6 months
Overall survival	All cause mortality	6-12 months
Response rate		3-6 month
Quality of life measured by FACT-L/LCS 4.0		1 year
Neurocognitive effects	Evaluated according to Mini-Mental Status Examination	3-6 months

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): June 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: January 10, 2012
• First Submitted That Met QC Criteria: January 19, 2012
• First Posted (ESTIMATE): January 25, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): February 17, 2014
• Last Update Submitted That Met QC Criteria: February 13, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Safety; NSCLC; WBRT; EGFR-TKI; Icotinib
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: BD-IC-IV04