A Study to Determine the Efficiency For Brain Metastasis NSCLC Patients Treated With Icotinib Alone or Combined With Radiation Therapy

Phase 3

• Conditions: Non Small Cell Lung Cancer; Brain Metastases
• Interventions: Drug: Icotinib; Radiation: SRS/WBRT/HA-WBRT/SMART

• Registration Number: NCT04058704
• Lead Sponsor: Betta Pharmaceuticals Co., Ltd.

Brief Summary

The purpose of this study is to evaluate the efficacy of icotinib alone or in combination with radiation therapy for NSCLC patients harboring EGFR mutation with brain metastases. The primary endpoint is overall survival .

Detailed Description

Non-small cell lung cancer (NSCLC) is one of the malignant tumors with the highest incidence of brain metastases, and most patients died due to the progression of brain metastases. Some research show that icotinib combined with radiation therapy can improve the efficiency of NSCLC with brain metastases, but there is still controversial about the timing of radiation therapy intervention . This study is a prospective, multi-center, randomized, controlled trial of icotinib combined with early intervention or late intervention radiation therapy for NSCLC patients harboring EGFR mutation with brain metastases. They will be treated with icotinib and divided into 2 groups. Group 1: the radiation therapy will start within 1 month after icotinib treatment; Group2: the patients will be treated with icotinib first, radiation therapy intervene if disease progress.

Study Timeline

• Study Start: 2018-07-20
• Status Verified: 2019-08
• Study First Submitted: 2019-08-11
• Study First Submitted QC: 2019-08-13
• Last Update Submitted: 2019-08-13
• Study First Posted: 2019-08-15
• Last Update Posted: 2019-08-15
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 296

Inclusion Criteria

• Histological or cytological confirmation of non-small-cell lung cancer (NSCLC)
• Positive EGFR mutation（Ex19del or 21L858R）
• Primary diagnosis of brain metastases
• Have one or more measurable encephalic lesions according to RECIST
• Extracranial transfer organ≤3
• ECGO:0-2
• 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 : gefitinib, erlotinib, icotinib，or any other TKI
• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early intervention	Icotinib	Icotinib is administered orally three times per day. Radiation therapy (SRS/ WBRT/ HA-WBRT/SMART) start in 1 month since take icotinib orally.
Late intervention	Icotinib	Icotinib is administered orally three times per day. Until emerge the progression of the disease, then is given radiation therapy (SRS/WBRT/HA-WBRT/SMART)
Late intervention	SRS/WBRT/HA-WBRT/SMART	Icotinib is administered orally three times per day. Until emerge the progression of the disease, then is given radiation therapy (SRS/WBRT/HA-WBRT/SMART)
Early intervention	SRS/WBRT/HA-WBRT/SMART	Icotinib is administered orally three times per day. Radiation therapy (SRS/ WBRT/ HA-WBRT/SMART) start in 1 month since take icotinib orally.

Primary Outcome Measures

Name	Time	Method
Overall Survival	from date of randomization until the date of death, assessed up to 36 months.

Secondary Outcome Measures

Name	Time	Method
Neurocognitive function changes measured by MMSE	from date of randomization until the date of death from any cause, assessed up to 36 months	measured by MMSE
Quality of life measured by FACT-L/LCS 4.0	from date of randomization until the date of death from any cause, assessed up to 36 months	measured by FACT-L/LCS 4.0
Progression-free survival of intracranial lesions	from date of randomization until the date of progression, assessed up to 10 months
disease control rate of intracranial lesions	from date of randomization until the date of progression, assessed up to 18 months
Observing acute and late toxicity assessed by CTCAE v4.0	from date of randomization until the date of death from any cause, assessed up to 36 months	Assessed by CTCAE v4.0

Trial Locations

Locations (1)

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China