A Phase 2 Trial of Almonertinib With Concurrent Radiotherapy in The Treatment of Local Advanced EGFR-mutant NSCLC

Phase 2

• Conditions: Non Small Cell Lung Cancer; Stage III NSCLC; EGFR Activating Mutation
• Interventions: Drug: Almonertinib

• Registration Number: NCT04636593
• Lead Sponsor: First People's Hospital of Hangzhou

Brief Summary

Previous clinical studies showed there is a potential value of EGFR-TKI in local advanced EGFR-mutant NSCLC, while the risk of radiation pneumonia in combination of EGFR-TKI with thoracic radiotherapy is unknown. This study aims to explore the safety and efficacy of concurrent almonertinib, a new third-generation EGFR-TKI drug, with radiotherapy in local advanced EGFR-mutant NSCLC patients.

Detailed Description

Doublet platinum-based therapy combined with radiotherapy remains the standard treatment for first-line management of unresectable stage III NSCLC patients, regardless of the EGFR mutation status. But the 5-year survival rate is not satisfying. Previous clinical studies showed there is a potential value but also a high risk of radiation pneumonia in treatment regimens of combination TKI with radiotherapy. This study intends to explore the safety and efficacy of concurrent almonertinib, a new third-generation EGFR-TKI drug, with radiotherapy in EGFR-sensitive mutated locally advanced NSCLC patients.

Study Timeline

• Study Start: 2020-08-01
• Study First Submitted: 2020-11-15
• Study First Submitted QC: 2020-11-15
• Study First Posted: 2020-11-19
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-08
• Last Update Posted: 2021-01-12
• Primary Completion: 2021-12-31
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

• Confirmed histologically or pathologically as non-small cell lung cancer;
• According to the eighth edition of the 2015 IASLC international lung cancer staging, imaging staging assessed as inoperable stage III patients (according to the eighth edition of the 2015 IASLC international lung cancer staging);
• Blood or tissue EGFR detection is Exon 19 deletion or L858R mutation;
• Have not received systemic anti-tumor therapy;
• FEV1>0.75L;
• Age ≥ 18 years old;
• ECOG PS score ≤ 2;
• Estimated survival period ≥ 6 months;
• Women must undergo surgical sterilization, post-menopausal, or take contraceptive measures during the treatment period and within 3 months after the end;
• Sign the informed consent form.

Exclusion Criteria

• Previously received other anti-tumor treatment, including almonertinib or other EGFR-TKI drugs;
• Contraindications for radiotherapy such as uncontrolled systemic lupus erythematosus, scleroderma or other connective tissue diseases;
• Other malignant tumors within 5 years (except for non-melanoma skin cancer and cervical cancer);
• Any medical or non-medical reasons prevent the patient from continuing to participate in the research;
• It is expected that the patient will not be able to comply with the research procedures, restrictions and requirements, and researchers determine that the patient is not suitable for participating in the trial;
• Currently receiving (or unable to stop using it before receiving the first dose of study treatment) drugs or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks ago);
• The patient is taking any drugs that prolong the QT interval, and the drug cannot be stopped before the treatment of almonertinib;
• Patients with lung V20 > 28% even after two-month almonertinib treatment.
• Pregnancy or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Induction group	Almonertinib	If the lung V20 of initial radiation plan is equal to or more than 28%, then the patient will receive 2 months almonertinib before concurrent thoracic radiotherapy
Concurrent group	Almonertinib	If the lung V20 of initial radiation plan is less than 28%, then the patient will receive concurrent thoracic radiotherapy with almonertinib.

Primary Outcome Measures

Name	Time	Method
RP(≥3)	6 months	incidence of radiation pneumonitis (≥ grade 3) within 6 month after Radiotherapy

Secondary Outcome Measures

Name	Time	Method
OS	2 years	overall survival (OS) intervals from treatment to death or last follow-uo
LCR	1 years	local control rate
PFS	2 years	progression-free survival (PFS) defines as intervals from treatment to disease progression or death

Trial Locations

Locations (1)

Hangzhou Cancer hospital; 🇨🇳 Hangzhou, Zhejiang, China