Neoadjuvant Targeted Therapy in Patients With Resectable EGFR-mutated Lung Squamous Cell Carcinoma

Official title

Osimertinib as Neoadjuvant Therapy in Patients With Resectable Stage II-IIIB EGFR-mutated Lung Squamous Cell Carcinoma: A Single-centre, Single-arm, Phase 2 Trial

Overview

Previous trials, such as ADURA and CTONG, have demonstrated the benefits of neoadjuvant targeted therapy in patient with EGFR mutations , which can effectively reduce the extent of tumors and improve the survival outcomes. However, clinical trials of neoadjuvant targeted therapy in NSCLC have rarely enrolled patients with EGFR-mutated lung squamous cell carcinoma due to its rarity, which means that the safety and feasibility of neoadjuvant osimertinib in patients with resectable stage II-IIIB EGFR-mutated lung squamous cell carcinoma remains controversial.

Detailed description

This trial aims to investigated the safety and feasibility of neoadjuvant osimertinib in patients with resectable stage II-IIIB EGFR-mutated lung squamous cell carcinoma.

Interventions

• Drug Osimertinib
  Patients with resectable stage II-IIIB EGFR-mutated lung squamous cell carcinoma will receive Osimertinib ( 80mg/d, ≥9 weeks).

Primary outcome measures

• Objective Response Rate, ORR [Time frame: analysis is completed 4 weeks after neoadjuvant treatment]
• Safety: frequency of severe adverse events [Time frame: from the participants enrolling to 30 days after the last drug administration or 30 days after surgery.]

Secondary outcome measures (6)

• Major pathologic response, MPR [Time frame: analysis is completed 4 weeks after surgery]
• R0 rate [Time frame: analysis is completed 4 weeks after surgery]
• Progression-free survival (PFS) [Time frame: 2 years]
• Overall survival (OS) [Time frame: 5 years]
• Disease control rate (DCR) [Time frame: 2 years]
• Duration of remission (DOR) [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Chest CT and pathological examination confirmed as resectable II-IIIB lung squamous cell carcinoma;
• Gene text confirmed EGFR mutation;
• PET-CT confirmed no metastasis;
• ECOG physical status score 0-1;
• Age ≥ 18 years;
• Have one measurable lesion at least;
• Good function of other major organs (liver, kidney, blood system, etc.):-absolute neutrophil count ((ANC) ≥ 1.5 × 109), platelet (≥ 100 × 109), hemoglobin (≥ 90g/L). Note: patients shall not receive blood transfusion or growth factor support within 14 days before blood collection during the screening period;-International standardized ratio (INR) or prothrombin time (PT) ≤ 1.5 × normal upper limit (ULN);-activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;- serum total bilirubin ≤ 1.5 × ULN (Gilbert syndrome patients with total bilirubin must be < 3×ULN). Fertile female patients with aspartate and alanine aminotransferase (AST and ALT) ≤ 2.5 × ULN, or liver metastasis with AST and ALT ≤ 5 × ULN
• Fertile female patients must voluntarily take effective contraceptive measures more than 120 days after treatment, and the urine or serum pregnancy test results less than 7 days before entering the group were negative. Unsterilized male patients must voluntarily take effective contraceptive measures ≥ 120 days after treatment;
• Sign informed consent.

Exclusion criteria

• Patients with other malignant tumors in the five years before the start of this trial.
• Complicated with unstable systemic diseases, including active infections, uncontrolled hypertension, unstable angina pectoris, congestive heart failure \[higher than II (New York College of Cardiology)\], severe arrhythmias, liver, kidney or metabolic diseases;
• Active, known or suspected autoimmune diseases, or autoimmune paraneoplastic syndrome requiring systemic treatment;
• A history of active bleeding or embolism within 6 months, or received thrombolysis or anticoagulation therapy, or the researchers believe that there is an obvious tendency of gastrointestinal bleeding (such as esophageal varices have the risk of bleeding, local active ulcer lesions, etc.);
• Allergic to experimental drugs;
• Complicated with HIV infection or active hepatitis.
• Vaccination within 4 weeks before the start of this trial;
• Those who had undergone other major operations or severe injuries within the previous 2 months;
• Clinically uncontrolled pleural effusion or ascites requiring pleural or abdominal puncture drainage within 2 weeks before admission;
• Pregnant or lactating women;
• Those with neurological diseases or mental disorders;
• Participated in another therapeutic clinical study at the same time;
• Other researchers did not consider it appropriate to enroll in the group.

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

• The First Affiliated Hospital of Guangzhou Medical University — Guangzhou

Identifiers

NCT: NCT06383728 · ES-2024-014-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗