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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05754736
• Other study ID #: MT-005
• Status: Recruiting
• Phase: Phase 2
• Start date: December 1, 2022
• Est. completion date: December 1, 2025

Study information

• Verified date: February 2023
• Source: The Second Affiliated Hospital of Shandong First Medical University
• Contact: Ying Kong
• Phone: 13153882807
• Email: kongyingcoco[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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); ? 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. ? Predicted survival =3 months; ? ECOG score 0-1; ? The main organs (liver, kidney, heart) function normally. ? 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; ? with hemoptysis symptoms; ? Abnormal coagulation function (INR>1.5, APTT>1.5 ULN), with bleeding tendency; ? Have a history of psychotropic drug abuse and can not abstain or have mental disorders; ?According 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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-small Cell Lung Cancer

Intervention

Drug:
• Ametinib combined with bevacizumab
Ametinib 110mg po qd bevacizumab 15mg/kg ivdrip q3w

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Shandong First Medical University	Tai'an	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
The Second Affiliated Hospital of Shandong First Medical University

Country where clinical trial is conducted

China, 

References & Publications (3)

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 M — View Citation

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. Neurologi — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	Overall Survival	Time from randomization to death from any cause	3 year
Secondary	Quality of life score	Quantitative scoring system for patients' self-subjective self-assessment of current symptom tolerance	3 year
Secondary	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