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

NCT05132985 | Not Yet Recruiting Phase 2

• 1 other identifier: NIC-0102
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

NSCLC, EGFR, Icotinib

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to approximately 30 months

Secondary Outcomes (5)

• Pathological complete response (pCR)

  Up to approximately 30 months

• Objective response rate(ORR)

  Up to approximately 30 months

• R0 resection rate

  Up to approximately 30 months

• Disease-free survival(DFS)

  Up to approximately 72 months

• Overall survival(OS)

  Up to approximately 72 months

Study Arms (1)

Icotinib+chemotherapy

EXPERIMENTAL

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

Drug: Icotinib; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed

Interventions

Icotinib DRUG

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

Also known as: Conmana

Icotinib+chemotherapy

Cisplatin DRUG

75 mg/m2 (IV，Q3W)

Icotinib+chemotherapy

Carboplatin DRUG

AUC 5 (IV, Q3W)

Icotinib+chemotherapy

Pemetrexed DRUG

500 mg/m2 (IV, Q3W)

Icotinib+chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Liaoning Cancer Hospital & Institute: lead

Study Sites (1)

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, 110000, China

Location

Related Publications (7)

• NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data. Lancet. 2014 May 3;383(9928):1561-71. doi: 10.1016/S0140-6736(13)62159-5. Epub 2014 Feb 25.

  PMID: 24576776 BACKGROUND

• Giovannetti E, Lemos C, Tekle C, Smid K, Nannizzi S, Rodriguez JA, Ricciardi S, Danesi R, Giaccone G, Peters GJ. Molecular mechanisms underlying the synergistic interaction of erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, with the multitargeted antifolate pemetrexed in non-small-cell lung cancer cells. Mol Pharmacol. 2008 Apr;73(4):1290-300. doi: 10.1124/mol.107.042382. Epub 2008 Jan 10.

  PMID: 18187583 BACKGROUND

• La Monica S, Madeddu D, Tiseo M, Vivo V, Galetti M, Cretella D, Bonelli M, Fumarola C, Cavazzoni A, Falco A, Gervasi A, Lagrasta CA, Naldi N, Barocelli E, Ardizzoni A, Quaini F, Petronini PG, Alfieri R. Combination of Gefitinib and Pemetrexed Prevents the Acquisition of TKI Resistance in NSCLC Cell Lines Carrying EGFR-Activating Mutation. J Thorac Oncol. 2016 Jul;11(7):1051-63. doi: 10.1016/j.jtho.2016.03.006. Epub 2016 Mar 19.

  PMID: 27006151 BACKGROUND

• Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized Phase II Trial of Gefitinib With and Without Pemetrexed as First-Line Therapy in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. doi: 10.1200/JCO.2016.66.9218. Epub 2016 Aug 9.

  PMID: 27507876 BACKGROUND

• Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, Takahashi K, Fujita Y, Harada T, Minato K, Takamura K, Hagiwara K, Kobayashi K, Nukiwa T, Inoue A; North-East Japan Study Group. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. J Clin Oncol. 2020 Jan 10;38(2):115-123. doi: 10.1200/JCO.19.01488. Epub 2019 Nov 4.

  PMID: 31682542 BACKGROUND

• Zhong WZ, Chen KN, Chen C, Gu CD, Wang J, Yang XN, Mao WM, Wang Q, Qiao GB, Cheng Y, Xu L, Wang CL, Chen MW, Kang X, Yan W, Yan HH, Liao RQ, Yang JJ, Zhang XC, Zhou Q, Wu YL. Erlotinib Versus Gemcitabine Plus Cisplatin as Neoadjuvant Treatment of Stage IIIA-N2 EGFR-Mutant Non-Small-Cell Lung Cancer (EMERGING-CTONG 1103): A Randomized Phase II Study. J Clin Oncol. 2019 Sep 1;37(25):2235-2245. doi: 10.1200/JCO.19.00075. Epub 2019 Jun 13.

  PMID: 31194613 BACKGROUND

• Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WE, Nicholson AG, Groome P, Mitchell A, Bolejack V; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Advisory Boards and Participating Institutions. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016 Jan;11(1):39-51. doi: 10.1016/j.jtho.2015.09.009.

  PMID: 26762738 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

icotinib; Cisplatin; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Hongxu Liu, Doctor

  Liaoning Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 14, 2021
• First Posted: November 24, 2021
• Study Start: January 1, 2022
• Primary Completion: July 1, 2024
• Study Completion (Estimated): January 1, 2028
• Last Updated: December 10, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)