High Dose Icotinib With Sequential SRS For NSCLC Patients Harboring EGFR Mutation With Brain Metastases

A Phase II Study to Determine the Efficacy and Safety of High Dose Icotinib Combined With Stereotatic Radiosurgery for NSCLC Patients Harboring EGFR Mutation With Brain Metastases

This trail is designed to assess the efficacy and safety of high dose Iconitib combined with SRS for NSCLC patients harboring EGFR mutation with brain metastases.

Study Overview

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

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 to brain metastases patients.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital
      • Contact: YOU LU, M.D.
      • Principal Investigator: YOU LU, M.D.

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.
• Less than 10 sites of intracranial metastases, or the longest diameter of the intracranial lesion is less than 4cm.
• Positive EGFR mutation（Ex19del or 21L858R）.
• Life expectancy ≥3months.
• Have one or more measurable encephalic lesions according to RECIST.
• The patient has not received radiotherapy for the head or extracranial target lesions before.
• Adequate hematological function: Absolute neutrophil count (ANC) ≥1.5 x 109/L, and Platelet count ≥100 x 109/L.
• Adequate renal function: Serum creatinine ≤1.5 x ULN, or ≥ 50 ml/min.
• Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) and Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) < 2.5 x ULN in the absence of liver metastases, or < 5 x ULN in case of liver metastases.
• Female subjects should not be pregnant.
• All human subjects should able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
• Written informed consent provided.

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.
• Allergic to Icotinib.
• Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or have active peptic ulcer disease.
• Pregnancy or breast-feeding women.
• Participate in the other anti-tumor clinical trials in 4 weeks.
• have quit from the trail before.
• Any other serious underlying medical, psychological and other condition that, in the judgment of the investigator, may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

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 375mg Tid; The human subject gets icotinib 375mg, Tid until intracranial PD or intolerable toxicity reaction.	Drug: Icotinib; 375 mg Tid (1125 mg per day) until intracranial PD.; Radiation: SRS; If intracranial PD, then the subjects get stereotatic radiosurgery （30Gy/3f) combined with Icotinib 375mg Tid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
intracranial progression-free survival	from date of randomization until the date of first documented intracranial progression, assessed up to 12 months.

Secondary Outcome Measures

Outcome Measure	Time Frame
progress-free survival	from date of randomization until the date of extracranial progression, assessed up to 18 months.
overall survival	from date of randomization until the date of death, assessed up to 36 months.
objective response rate	from date of randomization until the date of progression, assessed up to 12 months.
disease control rate	from date of randomization until the date of progression, assessed up to 18 months.
Quality of life measured by FACT-L/LCS 4.0 and FACT-Br	from date of randomization until the date of death from any cause, assessed up to 36 months.

Other Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-related adverse events as assessed by NCI-CJ-CAE3.0	from date of randomization until the date of death, assessed up to 2 months.

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.
• Investigators: Principal Investigator: YOU LU, M.D., West China Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (ANTICIPATED): December 1, 2021
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: March 29, 2016
• First Submitted That Met QC Criteria: March 31, 2016
• First Posted (ESTIMATE): April 1, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 19, 2019
• Last Update Submitted That Met QC Criteria: February 15, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: NSCLC; radiotherapy; SRS; 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-IV-65

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED