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

Sponsor

Betta Pharmaceuticals Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04058704

Collaborator

(none)

296

Enrollment

Location

Arms

53.4

Anticipated Duration (Months)

5.5

Patients Per Site Per Month

Study Details

Study Description

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 .

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer Brain Metastases	Drug: Icotinib Radiation: SRS/WBRT/HA-WBRT/SMART	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

296 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multi-center, Prospective Study to Determine the Efficiency of Icotinib Combined With Radiation Therapy Early Intervention or Late Intervention For NSCLC Patients With Brain Metastases and EGFR(Epidermal Growth Factor Receptor) Mutation

Actual Study Start Date :

Jul 20, 2018

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Early intervention Icotinib is administered orally three times per day. Radiation therapy (SRS/ WBRT/ HA-WBRT/SMART) start in 1 month since take icotinib orally.	Drug: Icotinib 125mg Tid/375mg per day Radiation: SRS/WBRT/HA-WBRT/SMART >3 with WBRT/HA-WBRT/SMART or 1-3 with SRS
Experimental: Late intervention 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)	Drug: Icotinib 125mg Tid/375mg per day Radiation: SRS/WBRT/HA-WBRT/SMART >3 with WBRT/HA-WBRT/SMART or 1-3 with SRS

Arm

Intervention/Treatment

Experimental: Early intervention

Icotinib is administered orally three times per day. Radiation therapy (SRS/ WBRT/ HA-WBRT/SMART) start in 1 month since take icotinib orally.

Drug: Icotinib

125mg Tid/375mg per day

Radiation: SRS/WBRT/HA-WBRT/SMART

>3 with WBRT/HA-WBRT/SMART or 1-3 with SRS

Experimental: Late intervention

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)

Drug: Icotinib

125mg Tid/375mg per day

Radiation: SRS/WBRT/HA-WBRT/SMART

>3 with WBRT/HA-WBRT/SMART or 1-3 with SRS

Outcome Measures

Primary Outcome Measures

Overall Survival [from date of randomization until the date of death, assessed up to 36 months.]

Secondary Outcome Measures

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]
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
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.