Phase II Trial of Double Dose of Icotinib in Treating Brain Metastases From Non-small Cell Lung Cancer

Brain metastases, a common complication,occur in 25-40% of patients with non-small cell lung cancer (NSCLC). Whole-brain radiation therapy(WBRT) and Stereotactic Radiosurgery (SRS) are important approaches to the treatment of brain metastases from NSCLC. Known to us, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can pass through the blood-brain barrier and show promising antitumor activity against brain metastases from NSCLC, especially for EGFR mutation patients. However, due to the lower concentration of tyrosine kinase inhibitors (TKIs) in the cerebrospinal fluid and its inevitable emergence of drug resistance, brain metastases will be refractory or resistant to standard-dose EGFR inhibitors. Icotinib is one agent of EGFR-TKIs. The previous studies have shown that the Icotinib conventional dose (125mg, TID) is far from reached its maximum tolerable dose. It is a challenge whether the further dose escalation of Icotinib will enhance its concentration in cerebrospinal fluid and thereby improve its therapeutic effect. Here the investigators examine the therapeutic effect and side-effect of double dose of Icitinib in treating patients with brain metastases from NSCLC who have suffered from the failure of conventional dose treatment.

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer; Brain Metastases
• Intervention / Treatment: Drug: Icotinib

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Recruiting
      • Zhejiang Cancer Hospital
      • Contact: Yun Fan, MD; Phone Number: 0086-571-88122192; Email: fanyun@csco.org.cn

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 cytologic diagnosis of NSCLC
• Patients with disease progression after local treatment(WBRT and/or SRS) combined with Icotinib treatment.
• Patients with EGFR mutation or the lesions that remains stable for more than 3 months after local treatment(WBRT and/or SRS) combined with Icotinib treatment.
• ECOG performance status 0-2
• Doctors consider the patients will not benefit from local treatment(WBRT and/or SRS)
• Expected survival of greater than 3 months
• Age: 18-75 years
• The patients with key organs maintenance of basic function: Hemoglobin ≥ 9g/dL, White Blood Cell ≥ 3×109/L, Neutrophil count ≥ 1.5×109/L, platelets ≥ 80×109/L, total bilirubin < 1.5 times of the upper normal values, Alanine transaminase (ALT) and aspartate transaminase (AST) < 2.5 of the upper normal values, the serum creatinine < 1.5 times of the upper normal values
• Signed informed consent document on file.

Exclusion Criteria:

• Brain metastasis without local treatment before
• Patients without the treatment of Icotinib before or the therapeutic time less than 3 months
• More than 3 extracranial organs have metastatic lesions
• The patient with other type malignant tumors before
• The patient with fertility capacity, but without contraceptive application

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Icotinib,Brain metastases	Drug: Icotinib; The patients will receive Icotinib in doses of 250mg thrice per day until disease progression or undue toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival (intracranial lesions)	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	3 years
Partial response rate of intracranial lesions	2 years
Partial response rate of extracranial lesion	2 years
Health-related quality of life quality	2 years
number of adverse events such as skin rash,diarrhea ,abnormal liver function and so on	2 years

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital
• Investigators: Principal Investigator: Weimin Mao, MD, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Anticipated): February 1, 2015
• Study Completion (Anticipated): September 1, 2015

Study Registration Dates

• First Submitted: August 27, 2012
• First Submitted That Met QC Criteria: September 19, 2012
• First Posted (Estimate): September 20, 2012

Study Record Updates

• Last Update Posted (Estimate): September 20, 2012
• Last Update Submitted That Met QC Criteria: September 19, 2012
• Last Verified: September 1, 2012

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
• Other Study ID Numbers: ZhejiangCH-LCBM-1202