Clinical Study of Ametinib Combined With Bevacizumab in First-line Treatment of Advanced NSCLC With EGFR-mutations.

Phase 2

Recruiting

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: Ametinib combined with bevacizumab

• Registration Number: NCT05754736
• Lead Sponsor: The Second Affiliated Hospital of Shandong First Medical University

Brief Summary

To explore the intracranial/extracranial ORR, PFS, QoL, safety, dynamic changes of tissue, cerebrospinal fluid, and plasma DNA in patients with newly diagnosed advanced NSCLC with EGFR mutation with/without brain metastasis given first-line treatment with almonertinib combined with bevacizumab at the initial stage of treatment, during treatment and after drug resistance, and the correlation between early clearance of sensitive mutations and survival.

Detailed Description

This is a one-arm prospective study to evaluate the first-line treatment of amitinib in combination with bevacizumab in patients with advanced NSCLC with EGFR mutations Effectiveness and safety. Subjects received amitinib and bevacizumab during the treatment cycle and were evaluated for efficacy every 6-8 weeks. Subject receives medication until disease progression, intolerable toxicity, or withdrawal of informed consent. The primary endpoint was progression-free survival as measured by the solid tumor Response Assessment Criteria (RECIST v1.1). Primary endpoints included objective response rate (ORR), progression-free period (PFS), and secondary endpoints included objective response rate (iORR), progression-free period (iPFS), overall survival (OS), quality of life (QoL), and safety.

Study Timeline

• Study Start: 2022-12-01
• Status Verified: 2023-02
• Study First Submitted: 2023-02-22
• Study First Submitted QC: 2023-02-22
• Last Update Submitted: 2023-02-22
• Study First Posted: 2023-03-06
• Last Update Posted: 2023-03-06
• Primary Completion: 2023-12-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Male or female, ≥18 years old and ≤75years old;

  • Non-squamous non-small cell lung cancer (NSCLC) confirmed by pathology (including histology or cytology); ③ EGFR mutation positive (exon 19 deletion or exon 21 L858R mutation); (4) ≥3 intracranial metastases, asymptomatic brain metastases; (5) Never received antitumor therapy before;

    • There was at least 1 measurable intracranial and extracranial lesion in CT/MRI according to RECIST1.1 criteria.

      ⑦ Predicted survival ≥3 months;

      ⑧ ECOG score 0-1;

      ⑨ The main organs (liver, kidney, heart) function normally.

      ⑩ Sign informed consent forms.

Exclusion Criteria

• The intracranial metastases were oligometastases;

  • There are symptoms of increased intracranial pressure; (3) Previous or co-existing malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix); (4) Patients with hypertension and can not be reduced to the normal range after antihypertensive drug treatment, have grade I coronary heart disease, grade I arrhythmia and grade I cardiac insufficiency;

    • Patients with definite tendency to gastrointestinal bleeding; ⑥ with hemoptysis symptoms; ⑦ Abnormal coagulation function (INR>1.5, APTT>1.5 ULN), with bleeding tendency; ⑧ Have a history of psychotropic drug abuse and can not abstain or have mental disorders; ⑨According to the investigator's judgment, Patients who have a serious concomitant disease that endangers the patient's safety or affects the patient's completion of the study, and who have previous or current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, or severe impairment of lung function.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ametinib combined with bevacizumab	Ametinib combined with bevacizumab	Ametinib 110 mg po qd bevacizumab 15mg/kg ivdrip q3w

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	2 years	It refers to the proportion of patients (mainly solid tumors) whose tumor has shrunk to a certain extent and remained there for a certain period of time, including Complete Response (CR) and Partial Response (PR)
Progression Free Survival	2 years	The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse

Secondary Outcome Measures

Name	Time	Method
Overall Survival	3 year	Time from randomization to death from any cause
Intracranial Objective Response Rate	2 year	It refers to the proportion of patients with brain metastases，whose Intracranial tumor has shrunk to a certain extent and remained there for a certain period of time, including Complete Response (CR) and Partial Response (PR)
Intracranial Progression Free Survival	2 year	The length of time during and after the treatment of lung cancer, that a patient with brain metastases lives with the tumor but it does not get worse
Quality of life score	3 year	Quantitative scoring system for patients' self-subjective self-assessment of current symptom tolerance
Adverse event	3 year	It refers to all adverse medical events that occur after a subject receives an investigational drug, which may be manifested as symptoms, signs, diseases, or abnormalities in laboratory tests, but may not necessarily be causally related to the investigational drug; It refers to all adverse medical events that occur after a subject receives an investigational drug, which may be manifested as symptoms, signs, diseases, or abnormalities in laboratory tests, but may not necessarily be causally related to the investigational drug; It refers to all adverse medical events that occur after a subject receives an investigational drug, which may be manifested as symptoms, signs, diseases, or abnormalities in laboratory tests, but may not necessarily be causally related to the investigational drug

Trial Locations

Locations (1)

The Second Affiliated Hospital of Shandong First Medical University; 🇨🇳 Tai'an, Shandong, China