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

NCT ID: NCT05754736

Last Updated: 2023-03-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-01
• Study Completion Date: 2025-12-01

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.

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ametinib combined with bevacizumab

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

Group Type: EXPERIMENTAL

Ametinib combined with bevacizumab

Intervention Type: DRUG

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

Interventions

Ametinib combined with bevacizumab

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

Intervention Type: DRUG

Other Intervention Names

Third-generation TKI combined with antivascular targeting drug

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Second Affiliated Hospital of Shandong First Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Haiyan Liu

Role: PRINCIPAL_INVESTIGATOR

The Second Affiliated Hospital of Shandong First Medical University

Locations

The Second Affiliated Hospital of Shandong First Medical University

Tai’an, Shandong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Ying Kong

Role: CONTACT

kongyingcoco@163.com

13153882807

Facility Contacts

Zhensheng Fang

Role: primary

sdtatszhenhua@126.com

+86-0538-6236830

References

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.

Reference Type: RESULT

PMID: 32529128 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31292359 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31918343 (View on PubMed)

Other Identifiers

MT-005

Identifier Type: -

Identifier Source: org_study_id