Hypofractionated Brain Radiation In EGFR Mutated Adenocarcinoma Cranial Disease (Hybrid) (Hybrid)

Comparing Whole Brain Radiation With Hypofractionated Stereotactic RadioSurgery (HFSRS) in Patients With NSCL Brain Metastases

A multi-center phase III randomized controlled study to evaluate the efficacy of Hypofractionated SRS (HFSRS) along with EGFR-TKI in patients with brain metastasis from non-small cell lung cancer (NSCLC). Assuming that HFSRS is not inferior to EGFR-TKI concurrent with whole brain radiotherapy (WBRT), the primary end point is intracranial PFS (iPFS), while secondary outcomes included overall survival (OS), evaluation of cognitive function, quality of life (QoL) and adverse events.

Study Overview

• Status: Unknown
• Conditions: Stage IV EGFR Mutated NSCL With Brain Metastases
• Intervention / Treatment: Drug: Gefitinib 250mg po qd or Tarceva 150mg po qd or Icotinib 125mg po tid Other Name: Gefitinib/Tarceva/Icotinib; Radiation: WBRT; Radiation: HFSRS

Detailed Description

WBRT remains to be standard of care for NSCL patients. Long term survival from WBRT may have noticeable cognitive dysfunction. The EGFR TKI has reasonable control for intracranial disease, but the duration of EGFR TKI control disease is variable due to tendency of drug resistance. To maintain intracranial disease control and improve cognitive function, the investigators propose using hypofractionated SRS in multiple brain metastases or large brain lesions alone with TKI.

• Study Type: Interventional
• Enrollment (Anticipated): 325
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 710062
      • Recruiting
      • Sichuan PPH, Cancer Center
      • Contact: Yifeng Bai, MD PhD; Phone Number: 18183298718; Email: 15756285949@qq.com
      • Contact: Ming zeng, MD PhD; Phone Number: 008617708131336; Email: miller2002@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 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 4 cm.
• Positive EGFR mutation.
• Life expectancy ≥3months.
• Have one or more measurable encephalic lesions according to RECIST.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: WBRT along with TKI; Drug: EGFR-TKI Gefitinib 250mg po qd or Tarceva 150mg po qd or Icotinib 125mg po tid Other Name: Gefitinib/Tarceva/Icotinib Radiation: whole brain radiotherapy 3750Gy/15F Other Name: WBRT	Drug: Gefitinib 250mg po qd or Tarceva 150mg po qd or Icotinib 125mg po tid Other Name: Gefitinib/Tarceva/Icotinib; radiation given along with one of kind TKI; Other Names: EGFR-TKI; Radiation: WBRT; 3750 cGy in 15 fractions given within 3 weeks time.
Experimental: HFSRS with EGFR TKI; Drug: EGFR-TKI Gefitinib 250mg po qd or Tarceva 150mg po qd or Icotinib 125mg po tid Other Name: Gefitinib/Tarceva/Icotinib Radiation: whole brain radiotherapy 25 to 40 Gy/5F Other Name: HFSRS	Drug: Gefitinib 250mg po qd or Tarceva 150mg po qd or Icotinib 125mg po tid Other Name: Gefitinib/Tarceva/Icotinib; radiation given along with one of kind TKI; Other Names: EGFR-TKI; Radiation: HFSRS; All HFSRS given in 5 fractions. dose per fraction ranges from 5 to 8 Gy depending on the target volume and organs at risk tolerance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
iPFS	intracranial progression-free survival	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cognitive function	Neurocognitive effects evaluated according to Mini-Mental Status Examination Evaluated according to Mini-Mental Status Examination	18 month
Overall survival (OS)	Overall survival	18 months

Collaborators and Investigators

• Sponsor: Sichuan Provincial People's Hospital
• Investigators: Study Chair: Ming Zeng, MD PhD, Sichuan Provincial People Hospital, Sichuan Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Anticipated): March 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: August 25, 2016
• First Submitted That Met QC Criteria: August 29, 2016
• First Posted (Estimate): August 30, 2016

Study Record Updates

• Last Update Posted (Estimate): August 30, 2016
• Last Update Submitted That Met QC Criteria: August 29, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Gefitinib
• Other Study ID Numbers: Hybrid

Plan for Individual participant data (IPD)

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