Early or Delayed Intervention of Brain Radiotherapy Combined With Almonertinib in EGFR Mutated NSCLC With Brain Metastases

A Prospective, Multicenter, Randomized, Controlled Clinical Study of Early or Delayed Intervention of Brain Radiotherapy Combined With Almonertinib in EGFR Mutated NSCLC With Brain Metastases

This is a prospective, multicenter, randomized, controlled clinical study of NSCLC patients with intracranial oligo-metastatic EGFR-sensitive mutations treated with EGFR-TKI Almonertinib , according to the implementation time of brain radiotherapy. Patients were randomly divided into two groups, experimental group (early intervention group of brain radiotherapy) : the brain radiotherapy started within 1 month of TKI treatment, the brain radiotherapy here specifically refers to stereotactic radiotherapy; Control group (brain radiotherapy late intervention group) : Brain radiotherapy was given within 3 months after brain progression during TKI treatment. The differences in OS,iPFS, PFS, iORR, safety, neurocognitive function and quality of life between the two groups were compared.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases; Radiotherapy; EGFR Activating Mutation
• Intervention / Treatment: Radiation: brain radiotherapy; Drug: Almonertinib

• Study Type: Interventional
• Enrollment (Anticipated): 232
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Likun Chen, Ph.D; Phone Number: +8613798019964; Email: chenlk@sysucc.org.cn

Study Locations

• China
  • Guangzhou
    • Guangdong, Guangzhou, China, 510000
      • Recruiting
      • Sun-Yat-Sen university
      • Contact: Likun Chen; Phone Number: 13798019964; Email: chenlk@sysucc.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:

• Patients with histologically or cytologically confirmed non-small cell lung cancer;
• Initial diagnosis of intracranial oligometastases (no treatment after brain metastases) was defined as brain parenchymal metastases confirmed by MRI, the number of intracranial parenchymal metastases was less than 5, and the lesions were 3mm away from the optic nerve and brainstem; There must be at least one measurable lesion with a diameter of 5mm or more in the brain.
• EGFR sensitivity mutation (exon19del or exon21 L858R);
• Anti-EGFR-targeting drugs and other TKI drugs have not been used in the past;
• Age 18-75;

Inclusion criteria:

• A history (past or concurrent) of malignancies in other sites, excluding curable non-melanoma skin cancer and cervical carcinoma in situ;
• The subjects had received brain radiotherapy before enrollment;
• Patients whose lung lesions were surgically evaluated as resectable were not included if there was no metastasis in other parts of the body;
• Received EGFR inhibitors (including small molecule or monoclonal antibody therapy) or systematic anti-tumor therapy before treatment;
• Prior patients with interstitial lung disease, drug-induced interstitial disease, radiation pneumonia requiring hormone therapy, or any clinically proven active interstitial lung disease with idiopathic pulmonary fibrosis found on CT scan at baseline;
• Pregnant and lactating patients;
• MRI contraindicated patients;
• Patients who cannot receive oral administration, need intravenous high-energy nutrition, have undergone previous surgery that interferes with absorption, or have active digestive tract ulcers;
• The researchers judged that brain radiotherapy could not be received because of other head and facial diseases;
• Any unstable systemic disease (including active infection, poorly controlled hypertension, unstable angina, congestive heart failure, liver, kidney or metabolic disease).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: early intervention group of brain radiotherapy; the brain radiotherapy started within 1 month of almonertinib the brain radiotherapy here specifically refers to stereotactic radiotherapy	Radiation: brain radiotherapy; Patients were randomly divided into two groups, experimental group (early intervention group of brain radiotherapy) : the brain radiotherapy started within 1 month of TKI treatment, the brain radiotherapy here specifically refers to stereotactic radiotherapy; Control group (brain radiotherapy late intervention group) : Brain radiotherapy was given within 3 months after brain progression during TKI treatment.; Drug: Almonertinib; almonertinib po 110mg QD
Active Comparator: late intervention group of brain radiotherapy; Brain radiotherapy was given within 3 months after brain progression during almonertinib treatment	Drug: Almonertinib; almonertinib po 110mg QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	The time from randomization to death from any cause.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intracranial progression free survival	patients were randomized from the time of observation of intracranial disease progression or death from any cause	2 years
progression free survival	patients were randomized from the time of observation of systemic disease progression or death from any cause	2 years
intracranial objective response rate	proportion of patients with complete or partial response of intracranial lesions	6 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Likun Chen, SunYat-Sen University Cancer Center

Study record dates

Study Major Dates

• Study Start (Anticipated): March 15, 2023
• Primary Completion (Anticipated): December 31, 2028
• Study Completion (Anticipated): December 31, 2029

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: March 13, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

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
• Other Study ID Numbers: B2022-428-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No