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

Primary Purpose

Non-small Cell Lung Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Ametinib combined with bevacizumab
Sponsored by
The Second Affiliated Hospital of Shandong First Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The Second Affiliated Hospital of Shandong First Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ametinib combined with bevacizumab

Arm Description

Ametinib 110 mg po qd bevacizumab 15mg/kg ivdrip q3w

Outcomes

Primary Outcome Measures

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)
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

Secondary Outcome Measures

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)
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
Overall Survival
Time from randomization to death from any cause
Quality of life score
Quantitative scoring system for patients' self-subjective self-assessment of current symptom tolerance
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

Full Information

First Posted
February 22, 2023
Last Updated
February 22, 2023
Sponsor
The Second Affiliated Hospital of Shandong First Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT05754736
Brief Title
Clinical Study of Ametinib Combined With Bevacizumab in First-line Treatment of Advanced NSCLC With EGFR-mutations.
Official Title
Efficacy and Safety of Ametinib Combined With Bevacizumab in First-line Treatment of Non-oligometastatic Advanced NSCLC With EGFR-mutations.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2022 (Actual)
Primary Completion Date
December 1, 2023 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Second Affiliated Hospital of Shandong First Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ametinib combined with bevacizumab
Arm Type
Experimental
Arm Description
Ametinib 110 mg po qd bevacizumab 15mg/kg ivdrip q3w
Intervention Type
Drug
Intervention Name(s)
Ametinib combined with bevacizumab
Other Intervention Name(s)
Third-generation TKI combined with antivascular targeting drug
Intervention Description
Ametinib 110mg po qd bevacizumab 15mg/kg ivdrip q3w
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
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)
Time Frame
2 years
Title
Progression Free Survival
Description
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
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Intracranial Objective Response Rate
Description
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)
Time Frame
2 year
Title
Intracranial Progression Free Survival
Description
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
Time Frame
2 year
Title
Overall Survival
Description
Time from randomization to death from any cause
Time Frame
3 year
Title
Quality of life score
Description
Quantitative scoring system for patients' self-subjective self-assessment of current symptom tolerance
Time Frame
3 year
Title
Adverse event
Description
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
Time Frame
3 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ying Kong
Phone
13153882807
Email
kongyingcoco@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Haiyan Liu
Organizational Affiliation
The Second Affiliated Hospital of Shandong First Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Affiliated Hospital of Shandong First Medical University
City
Tai'an
State/Province
Shandong
ZIP/Postal Code
271000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhensheng Fang
Phone
+86-0538-6236830
Email
sdtatszhenhua@126.com
First Name & Middle Initial & Last Name & Degree
Haiyan Liu

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32529128
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. 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.
Results Reference
result
PubMed Identifier
31292359
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.
Results Reference
result
PubMed Identifier
31918343
Citation
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.
Results Reference
result

Learn more about this trial

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

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