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Neoadjuvant Icotinib With Chemotherapy for Epidermal Growth Factor Receptor(EGFR)-Mutated Resectable Lung Adenocarcinoma

Primary Purpose

NSCLC, EGF-R Positive Non-Small Cell Lung Cancer

Status

Not yet recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Icotinib

Cisplatin

Carboplatin

Pemetrexed

About this trial

This is an interventional treatment trial for NSCLC focused on measuring NSCLC, EGFR, Icotinib

Eligibility Criteria

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

Key Inclusion Criteria:

Written informed consent
Male or female, aged ≥18 years and ≤75 years
Histologically or cytologically documented lung adenocarcinoma with completely resectable disease (Stage II-IIIB N2, according to the 8th edition of the IASLC Staging Manual in Thoracic Oncology)
Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by an MDT evaluation
A tumor which harbors either Ex19del or L858R EGFR-TKI-sensitizing mutations, either alone
ECOG PS 0/1 at enrollment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing
Adequate organ and marrow function as defined by:
- Hemoglobin: ≥9.0 g/dL
- Absolute neutrophil count: ≥1.5 × 109/l
- Platelet count: ≥100 × 109/l
- Serum bilirubin: ≤1.5 ULN
- ALT and AST: ≤2.5 × ULN
- Creatinine clearance: ≥60 ml/min
Life expectancy of 6 months prior to randomization

Exclusion Criteria:

Prior treatment with systemic anti-cancer treatment for NSCLC, EGFR-TKI treatment or pre-operative radiotherapy
EGFR-TKI-sensitizing mutations with T790M
Mixed small cell and non-small-cell lung cancer histology
T4 tumors infiltrating the aorta, esophagus and/or heart
Bulky N2 disease
Candidates for segmentectomies or wedge resections only
Medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment or any evidence of clinically active ILD
Severe or uncontrolled systemic diseases/active infections, history of allogeneic organ transplantation, history of primary immunodeficiency, history of another primary malignancy

Sites / Locations

Liaoning Cancer Hospital & Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Icotinib+chemotherapy

Arm Description

Neoadjuvant chemotherapy (pemetrexed + carboplatin/cisplatin ) will start within 1-3 days from enrollment at 21-day (+/-3 days) intervals (Q3W) prior to surgery. Before surgery a tumor assessment will be done to exclude evidence of progression. Patients with radiographically stable disease or partial response may be considered for operation. Icotinib will be given as a neoadjuvant therapy before surgical resection. The recommended dose of Icotinib is 125mg 1tt(Take 1 tablet 3 times a day) orally. Surgery: Surgery must be done within the 3rd to 4th week (+7 days) from day 21 cycle 2 of neoadjuvant treatment. Adjuvant treatment: Patients receive additional 2 cycles of platinum-based doublet chemotherapy(Researcher decide) on day 1 with intercalated icotinib (D8-15) every 3 weeks, and continued icotinib for 2 years or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity

Outcomes

Primary Outcome Measures

Major pathological response(MPR)

Patients with tumors with ≤10% residual viable cancer cells (identified by routine hematoxylin and eosin staining) in the lung primary tumor after neoadjuvant treatment at the time of resection will be considered to have had an MPR.

Secondary Outcome Measures

Pathological complete response (pCR)

Patients with no residual viable tumor cells in any of the specimens (primary tumors, lymph nodes and margins) will be considered to have had a pCR.

Objective response rate(ORR)

defined as the sum of the complete response plus partial response divided by the total number of included patients.

R0 resection rate

Free resection margins proved microscopically;Systematic nodal dissection in its wider form or, if it is not performed, lobe-specific systematic nodal dissection;There should be no extracapsular extension of tumor in nodes removed separately or those at the margin of the main lung specimen. ;The highest mediastinal node that has been removed must be negative.

Disease-free survival(DFS)

DFS will be defined as the time from surgery until the first instance of disease recurrence (local or distant) or death due to any cause, whichever occurs first.

Overall survival(OS)

OS will be defined as the time from randomization until death due to any cause.

Full Information

NCT ID

NCT05132985

First Posted

November 14, 2021

Last Updated

November 28, 2021

Sponsor

Liaoning Tumor Hospital & Institute

1. Study Identification

Unique Protocol Identification Number

NCT05132985

Brief Title

Neoadjuvant Icotinib With Chemotherapy for Epidermal Growth Factor Receptor(EGFR)-Mutated Resectable Lung Adenocarcinoma

Official Title

Neoadjuvant Icotinib With Chemotherapy for Resectable Stage II-IIIB N2 EGFR Mutation-positive Lung Adenocarcinoma: A Phase II Study

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Not yet recruiting

Study Start Date

January 1, 2022 (Anticipated)

Primary Completion Date

July 1, 2024 (Anticipated)

Study Completion Date

January 1, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Liaoning Tumor Hospital & Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Icotinib is a first-generation inhibitor of EGFR-tyrosine kinase inhibitor in patients with non-small-cell lung cancer (NSCLC). Here we will evaluate neoadjuvant Icotinib with chemotherapy prior to surgery, in patients with resectable stage II-IIIB N2 EGFR mutation-positive NSCLC. The primary endpoint is centrally assessed major pathological response at the time of resection. Secondary endpoints include pathological complete response, objective response rate, R0 resection rate at the time of resection, disease-free survival, and overall survival. Safety and tolerability will also be assessed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

NSCLC, EGF-R Positive Non-Small Cell Lung Cancer

Keywords

NSCLC, EGFR, Icotinib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Icotinib+chemotherapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Icotinib

Other Intervention Name(s)

Conmana

Intervention Description

125mg 1tt(Take 1 tablet 3 times a day) orally.

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

75 mg/m2 (IV，Q3W)

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

AUC 5 (IV, Q3W)

Intervention Type

Drug

Intervention Name(s)

Pemetrexed

Intervention Description

500 mg/m2 (IV, Q3W)

Primary Outcome Measure Information:

Title

Major pathological response(MPR)

Description

Time Frame

Up to approximately 30 months

Secondary Outcome Measure Information:

Title

Pathological complete response (pCR)

Description

Patients with no residual viable tumor cells in any of the specimens (primary tumors, lymph nodes and margins) will be considered to have had a pCR.

Time Frame

Up to approximately 30 months

Title

Objective response rate(ORR)

Description

defined as the sum of the complete response plus partial response divided by the total number of included patients.

Time Frame

Up to approximately 30 months

Title

R0 resection rate

Description

Time Frame

Up to approximately 30 months

Title

Disease-free survival(DFS)

Description

DFS will be defined as the time from surgery until the first instance of disease recurrence (local or distant) or death due to any cause, whichever occurs first.

Time Frame

Up to approximately 72 months

Title

Overall survival(OS)

Description

OS will be defined as the time from randomization until death due to any cause.

Time Frame

Up to approximately 72 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Written informed consent Male or female, aged ≥18 years and ≤75 years Histologically or cytologically documented lung adenocarcinoma with completely resectable disease (Stage II-IIIB N2, according to the 8th edition of the IASLC Staging Manual in Thoracic Oncology) Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by an MDT evaluation A tumor which harbors either Ex19del or L858R EGFR-TKI-sensitizing mutations, either alone ECOG PS 0/1 at enrollment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing Adequate organ and marrow function as defined by: Hemoglobin: ≥9.0 g/dL Absolute neutrophil count: ≥1.5 × 109/l Platelet count: ≥100 × 109/l Serum bilirubin: ≤1.5 ULN ALT and AST: ≤2.5 × ULN Creatinine clearance: ≥60 ml/min Life expectancy of 6 months prior to randomization Exclusion Criteria: Prior treatment with systemic anti-cancer treatment for NSCLC, EGFR-TKI treatment or pre-operative radiotherapy EGFR-TKI-sensitizing mutations with T790M Mixed small cell and non-small-cell lung cancer histology T4 tumors infiltrating the aorta, esophagus and/or heart Bulky N2 disease Candidates for segmentectomies or wedge resections only Medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment or any evidence of clinically active ILD Severe or uncontrolled systemic diseases/active infections, history of allogeneic organ transplantation, history of primary immunodeficiency, history of another primary malignancy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hongxu Liu, Doctor

Organizational Affiliation

Liaoning Cancer Hospital & Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Liaoning Cancer Hospital & Institute

City

Shenyang

State/Province

Liaoning

ZIP/Postal Code

110000

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hongxu Liu, Doctor

Phone

18040097698

hxliu@cmu.edu.cn

First Name & Middle Initial & Last Name & Degree

Huan Wang, Doctor

Phone

18941634184

dr.wanghuan.cmu@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD

Citations:

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24576776

Citation

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Citation

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Results Reference

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Neoadjuvant Icotinib With Chemotherapy for Epidermal Growth Factor Receptor(EGFR)-Mutated Resectable Lung Adenocarcinoma

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