Clinical trial NCT05754736: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Non-small Cell Lung Cancer
Lead sponsor: The Second Affiliated Hospital of Shandong First Medical University
Sponsor class: OTHER
First posted: 2023-03-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Objective Response Rate
timeFrame: 2 years
measure: Progression Free Survival
timeFrame: 2 years
Secondary outcomes:
measure: Intracranial Objective Response Rate
timeFrame: 2 year
measure: Intracranial Progression Free Survival
timeFrame: 2 year
measure: Overall Survival
timeFrame: 3 year
measure: Quality of life score
timeFrame: 3 year
measure: Adverse event
timeFrame: 3 year
Other outcomes:
Locations:
city: Tai'an
country: China
facility: The Second Affiliated Hospital of Shandong First Medical University
state: Shandong
Study officials:
affiliation: The Second Affiliated Hospital of Shandong First Medical University
name: Haiyan Liu
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.