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

NSCLC Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05132985
• Other study ID #: NIC-0102
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 1, 2022
• Est. completion date: January 1, 2028

Study information

• Verified date: November 2021
• Source: Liaoning Tumor Hospital & Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 45
• Est. completion date: January 1, 2028
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• EGF-R Positive Non-Small Cell Lung Cancer
• NSCLC

Intervention

Drug:
• Icotinib
125mg 1tt(Take 1 tablet 3 times a day) orally.
• Cisplatin
75 mg/m2 (IV,Q3W)
• Carboplatin
AUC 5 (IV, Q3W)
• Pemetrexed
500 mg/m2 (IV, Q3W)

Locations

Country	Name	City	State
China	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning

Sponsors (1)

Lead Sponsor	Collaborator
Liaoning Tumor Hospital & Institute

Country where clinical trial is conducted

China, 

References & Publications (7)

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. — View Citation

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. — View Citation

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 I — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Up to approximately 30 months
Secondary	Objective response rate(ORR)	defined as the sum of the complete response plus partial response divided by the total number of included patients.	Up to approximately 30 months
Secondary	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.	Up to approximately 30 months
Secondary	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.	Up to approximately 72 months
Secondary	Overall survival(OS)	OS will be defined as the time from randomization until death due to any cause.	Up to approximately 72 months