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

Overview

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.

Interventions

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

Primary outcome measures

• Major pathological response(MPR) [Time frame: Up to approximately 30 months]

Secondary outcome measures (5)

• Pathological complete response (pCR) [Time frame: Up to approximately 30 months]
• Objective response rate(ORR) [Time frame: Up to approximately 30 months]
• R0 resection rate [Time frame: Up to approximately 30 months]
• Disease-free survival(DFS) [Time frame: Up to approximately 72 months]
• Overall survival(OS) [Time frame: Up to approximately 72 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Liaoning Cancer Hospital & Institute — Shenyang

Publications

• 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
• 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. PMID 18187583
• 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 PMID 27006151
• 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. Ep PMID 27507876
• 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. PMID 31682542
• 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: PMID 31194613
• 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 In PMID 26762738

Identifiers

NCT: NCT05132985 · NIC-0102

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗