Microwave Plus Chemotherapy Versus Chemotherapy for Advanced NSCLC

A Multicenter, Randomized, Open-label Phase III Trial of Microwave Plus Chemotherapy Versus Chemotherapy for Advanced NSCLC

This study is a multicenter, randomized, open-label Phase III trial that compares microwave plus chemotherapy versus chemotherapy in patients with advanced non-small cell lung cancer. The primary endpoint is progression free survival (PFS) and the key secondary endpoint is overall survival (OS). A total of 275 eligible patients will be randomized to receive either microwave ablation combinated with first-line platinum-based doublet chemotherapy（138） or first-line platinum-based doublet chemotherapy（137） in a 1:1 ratio until patients. The response of microwave ablation will be assessed by the expert consensus for thermal ablation of primary and metastatic lung tumors. Tumor response and progression will be assessed according to Response Evaluation Criteria in Solid Tumors（RECIST）1.1.

Patients will be randomized to treated with microwave ablation and chemotherapy or treated with chemotherapy alone.

Inclusion Criteria:

1. Diagnosis of advanced stage NSCLC (stage IIIB or IV) which is confirmed by histology or cytology methods.

2. Measurable disease other than the primary tumors site according to RECIST1.1.

3. Eastern Cooperative Oncology Group (ECOG) score of 0-2

4. Adequate organ function, defined as all of the following:

   1. Left ventricular ejection fraction >50% or within institution normal values.
   2. Absolute neutrophil count (ANC)>1500/mm3.
   3. Platelet count >75,000/mm3
   4. Estimated creatinine clearance>45m1/min.
   5. Total bilirubin<1.5 times institutional ULN (Patients with Gilbert's Syndrome total bilirubin must be <4 times institutional ULN).
   6. Aspartate amino transferase (AST) or alanine amino transferase (ALT) < three times the institutional upper limit of normal (ULN) (if related to liver metastases<five times institutional ULN).

5. Age ≥ 18 years.

6. Written informed consent that is consistent with International Conference on Harmonization (ICH)-Good Clinical Practice（GCP） guidelines.

Exclusion Criteria:

1. Previous anti-cancer treatments including chemotherapy, radiation therapy or targeted therapy..
2. Active symptomatic brain metastases. Dexamethasone therapy will be allowed if administered as a stable dose for at least 4 weeks before randomization.
3. Any other current malignancy or malignancy diagnosed within the past five (5) years.
4. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association （NYHA） classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to randomisation.
5. Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
6. Women of child-bearing potential and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry.
7. Female patients of childbearing potential who are nursing or are pregnant.
8. Patients unable to comply with the protocol in the opinion of the investigator.
9. Active hepatitis B infection (defined as presence of Hepatitis B DNA), active hepatitis C infection (defined as presence of Hepatitis C RNA) and/or known HIV carrier.
10. Known or suspected active drug or alcohol abuse in the opinion of the investigator.
11. Major surgery within 4 weeks of starting study treatment. Use of any investigational drug within 4 weeks of randomisation