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

Efficacy and Safety of Ametinib Combined With Bevacizumab in First-line Treatment of Non-oligometastatic Advanced NSCLC With EGFR-mutations.

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.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Ametinib combined with bevacizumab

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ying Kong; Phone Number: 13153882807; Email: kongyingcoco@163.com

Study Locations

• China
  • Shandong
    • Tai'an, Shandong, China, 271000
      • Recruiting
      • The Second Affiliated Hospital of Shandong First Medical University
      • Contact: Zhensheng Fang; Phone Number: +86-0538-6236830; Email: sdtatszhenhua@126.com
      • Principal Investigator: Haiyan Liu

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:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ametinib combined with bevacizumab; Ametinib 110 mg po qd bevacizumab 15mg/kg ivdrip q3w	Drug: Ametinib combined with bevacizumab; Ametinib 110mg po qd bevacizumab 15mg/kg ivdrip q3w; Other Names: Third-generation TKI combined with antivascular targeting drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	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)	2 years
Progression Free Survival	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	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial Objective Response Rate	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)	2 year
Intracranial Progression Free Survival	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	2 year
Overall Survival	Time from randomization to death from any cause	3 year
Quality of life score	Quantitative scoring system for patients' self-subjective self-assessment of current symptom tolerance	3 year
Adverse event	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	3 year

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Shandong First Medical University
• Investigators: Principal Investigator: Haiyan Liu, The Second Affiliated Hospital of Shandong First Medical University

Publications and helpful links

General Publications

• Ramotar M, Barnes S, Moraes F, Dasgupta A, Laperriere N, Millar BA, Berlin A, Conrad T, van Prooijen M, Damyanovich A, Heaton R, Cho YB, Coolens C, Liu G, Shepherd FA, Bradbury P, Leighl N, Bernstein M, Zadeh G, Kongkham P, Doherty M, Shultz DB. Neurological Death is Common in Patients With EGFR Mutant Non-Small Cell Lung Cancer Diagnosed With Brain Metastases. Adv Radiat Oncol. 2019 Nov 26;5(3):350-357. doi: 10.1016/j.adro.2019.11.002. eCollection 2020 May-Jun.
• Yoneda K, Imanishi N, Ichiki Y, Tanaka F. Treatment of Non-small Cell Lung Cancer with EGFR-mutations. J UOEH. 2019;41(2):153-163. doi: 10.7888/juoeh.41.153.
• Passiglia F, Pilotto S, Facchinetti F, Bertolaccini L, Del Re M, Ferrara R, Franchina T, Malapelle U, Menis J, Passaro A, Ramella S, Rossi G, Trisolini R, Novello S. Treatment of advanced non-small-cell lung cancer: The 2019 AIOM (Italian Association of Medical Oncology) clinical practice guidelines. Crit Rev Oncol Hematol. 2020 Feb;146:102858. doi: 10.1016/j.critrevonc.2019.102858. Epub 2019 Dec 28.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: February 22, 2023
• First Submitted That Met QC Criteria: February 22, 2023
• First Posted (Estimate): March 6, 2023

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Non-small Cell Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: MT-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No