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

Phase 2
Not yet recruiting
Conditions
NSCLC
EGF-R Positive Non-Small Cell Lung Cancer
Interventions
Registration Number
NCT05132985
Lead Sponsor
Liaoning Tumor Hospital & Institute
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
45
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Icotinib+chemotherapyCisplatinNeoadjuvant 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
Icotinib+chemotherapyIcotinibNeoadjuvant 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
Icotinib+chemotherapyCarboplatinNeoadjuvant 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
Icotinib+chemotherapyPemetrexedNeoadjuvant 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
Primary Outcome Measures
NameTimeMethod
Major pathological response(MPR)Up to approximately 30 months

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
NameTimeMethod
Disease-free survival(DFS)Up to approximately 72 months

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.

Pathological complete response (pCR)Up to approximately 30 months

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)Up to approximately 30 months

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

Overall survival(OS)Up to approximately 72 months

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

R0 resection rateUp to approximately 30 months

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.

Trial Locations

Locations (1)

Liaoning Cancer Hospital & Institute

🇨🇳

Shenyang, Liaoning, China

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