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

Almonertinib With Concurrent Radiotherapy in The Treatment of Unresectable, Stage Ⅲ Non-small-cell Lung Cancer Harboring EGFR Mutations: A PhaseⅡCohort Study

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.

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer; EGFR Activating Mutation; Stage III NSCLC
• Intervention / Treatment: Drug: Almonertinib

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 Type: Interventional
• Enrollment (Anticipated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shenglin Ma, M.D; Phone Number: 086-0571-56006013; Email: Mashenglin@medmail.com.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310002
      • Recruiting
      • Hangzhou Cancer Hospital
      • Contact: Bing Xia, M.D; Phone Number: 086-0571-56006388; Email: bxia_hzch@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Induction group; 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	Drug: Almonertinib; All enrolled patients underwent positioning CT scans before the initial treatment, a radiotherapy plan was made for each patient, and the lung V20 of each patient was calculated. Patients with lung V20 ≥ 28% were enrolled in group A: Almonertinib induction therapy was given for 2 months firstly, followed by Almonertinib combined with radiotherapy; patients with lung V20<28% were enrolled in group B: Almonertinib was synchronized with radiotherapy initially.; Other Names: Thoracic Radiotherapy
Experimental: Concurrent group; If the lung V20 of initial radiation plan is less than 28%, then the patient will receive concurrent thoracic radiotherapy with almonertinib.	Drug: Almonertinib; All enrolled patients underwent positioning CT scans before the initial treatment, a radiotherapy plan was made for each patient, and the lung V20 of each patient was calculated. Patients with lung V20 ≥ 28% were enrolled in group A: Almonertinib induction therapy was given for 2 months firstly, followed by Almonertinib combined with radiotherapy; patients with lung V20<28% were enrolled in group B: Almonertinib was synchronized with radiotherapy initially.; Other Names: Thoracic Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RP(≥3)	incidence of radiation pneumonitis (≥ grade 3) within 6 month after Radiotherapy	6 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: First People's Hospital of Hangzhou
• Collaborators: Hangzhou Cancer Hospital

Publications and helpful links

General Publications

• Zhu L, Zou C, Zhang Z, Wang J, Yang L, Rao C, Yang Z, Liang J, Xia B, Shenglin MA. Thoracic radiotherapy and concurrent almonertinib for unresectable stage III EGFR-mutated non-small-cell lung cancer: a phase 2 study. BMC Cancer. 2021 May 7;21(1):511. doi: 10.1186/s12885-021-08266-w.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: November 15, 2020
• First Submitted That Met QC Criteria: November 15, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 8, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: lung cancer; radiotherapy; EGFR-TKI; radiation pneumonitis; almonertinib
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: AlmonTRT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No