Clinical trial NCT04197076: Neoadjuvant Therapy in Resectable Non-Small Cell Lung Cancer Stages IIB-IIIB
Official title: An Open, Observational Clinical Study, 2-3 Cycles Treatment as Neoadjuvant Therapy for NSCLC With Stage IIB-IIIB
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Non Small Cell Lung Cancer
Lead sponsor: Shanghai Chest Hospital
Sponsor class: OTHER
First posted: 2019-12-12
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: NSCLC participants in stage IIB-IIIB(American Joint Committee on Cancer 8th edition criteria)

Brief summary: This study aims to investigate the efficacy and safety of targeted therapy and chemotherapy±immunotherapy as neoadjuvant therapy in stage IIB-IIIB NSCLC patients.（observational study）

Detailed description: This is an open, observational clinical study, 2-3 cycles treatment will be planned as neo-adjuvant therapy for NSCLC participants in stage IIB-IIIB.

Study design:

Newly diagnosed Resectable IIB-IIIB NSCLC EGFR/ALK/ROS1 TEST PD-L1 TEST Collect puncture biopsy tissue/ Blood sample in screening period Chest enhanced CT Conditions allowed， whole body PETCT Exam; Group A：Targeted therapy Tumors with Driver genes （EGFR/ALK/ROS1 Positive） 2 cycles（42 days; Group B：Immunotherapy Enroll Patients from 816 Research treated with Neoadjuvant immunotherapy Or, treated with immunotherapy in practice（with approval） Group C：Routine Chemotherapy Driver genes（EGFR/ALK/ROS1 Negative） and PD-L1 Test negative or unknown; Operation （within 6 Ws postoperation） Standard treatment， Allow adjuvant chemotherapy±radio therapy Collect resected tissue sample(Tumor T and Node N) /Blood sample; comparisons before and after treatment: Imaging：CT、PET-CT Sample：Tumor tissue、blood

Objective and End point:

1. Main objective and end point：DFS，pCR rate
2. Second objective and end point：OS
3. Exploratory objective and end point：cRR rate、relevant AE、Change of Scoring Scale、exploration for relevant biological indicators

Eligibility criteria: Inclusion Criteria:

1. Primary non-small cell lung cancer confirmed by cytology or histology
2. According to the TNM stage (8th Edition) of IASLC lung cancer, it is determined to be IIB-IIIB stage non-small cell lung cancer, which is considered to be resectable;
3. There must be at least one evaluable focus judged according to recist1.1 standard (the longest diameter on spiral CT is at least 10 mm, and the longest diameter on general CT is at least 20 mm)
4. ECOG PS 0 or 1
5. There are tumor samples available for gene detection (EGFR / ALK / ros1) and PD-L1 immunohistochemistry (IHC) in the subjects, and the tumor samples should be obtained within 3 months before enrollment.
6. If all suspected mediastinal lymph nodes (including those with pathological enlargement or FDG concentration on PET / CT) can be examined by EBUS, thoracoscopy or mediastinoscopy, further sampling is required for pathological confirmation.
7. Male or female, ≥ 18 years old
8. Adequate blood function: absolute neutrophil count (ANC) ≥ 2 × 109 / L, platelet count ≥ 100 × 109 / L and hemoglobin 110 ≥ 9 g / dl
9. Adequate liver function: total bilirubin ≤ upper limit of normal value (ULN); AST and alt ≤ upper limit of normal value (ULN); alkaline phosphatase ≤ upper limit of normal value (ULN)
10. Adequate renal function: serum creatinine ≤ upper limit of normal value (ULN) or calculated creatinine clearance ≥ 60ml / min
11. No anti-tumor drug treatment in the past
12. For patients who have had previous surgery, it is required that more than 4 weeks have passed since the start of study treatment, and the patients have recovered
13. Women with a full uterus must have negative pregnancy test results within 28 days before entering the study (unless it is 24 months after amenorrhea). If the pregnancy test is more than 7 days from the first administration, a urine pregnancy test is required for verification (within 7 days before the first administration)
14. Sign the informed consent form (the informed consent form needs to be approved by the independent ethics committee, and the informed consent of the patient should be obtained before starting any substantive trial procedure)

Exclusion Criteria:

1. Have other malignant tumors in the last 5 years
2. AST and / or ALT \> 2.5 times of the upper limit of normal value (ULN), with alkaline phosphatase \> 5 times of the upper limit of normal value (ULN)
3. Previously received radiotherapy
4. Previously used chemotherapy drugs, targeted and immunotherapy drugs (except bisphosphonates)
5. There are any uncontrolled systemic diseases, including active infection, uncontrolled hypertension, diabetes, unstable angina, congestive heart failure, myocardial infarction (within 1 year before treatment), serious arrhythmia requiring drug treatment, liver, kidney and metabolic diseases
6. Women in pregnancy or lactation
7. The patient (male or female) has the possibility of childbearing but is unwilling or does not take effective contraceptive measures
8. Receive the experimental treatment of other clinical studies at the same time (in the treatment period of clinical studies)
9. Known to be allergic to possible chemotherapy drugs
10. There is evidence of other diseases, neurological or metabolic dysfunction, abnormal physical examination or laboratory examination, and it is suspected that there may be a high risk of contraindications to the study drug or complications related to treatment

Primary outcomes:
measure: DFS: disease free survival
timeFrame: 36 months
measure: pCR: pathologic complete response
timeFrame: 36 months
Secondary outcomes:
measure: OS: Overall survival
timeFrame: 36 months
Other outcomes:
measure: cRR rates
timeFrame: approximately 10 weeks After surgery
measure: Safty AEs
timeFrame: 36 months
measure: Qol Quality of Life
timeFrame: 36 months
Locations:
city: Shanghai
country: China
facility: Oncology Department, Shanghai Chest Hospital
Study officials:
affiliation: Shanghai Chest Hospital
name: Shun Lu
role: STUDY_CHAIR
References:
citation: Gu L, Wang X, Sun Y, Xu Y, Niu X, Zhao R, Yao Y, Jian H, Han Y, Wei J, Chen Z, Lu S. An open, observational, three-arm clinical study of 2-3 cycles of treatment as neoadjuvant therapy in operable locally advanced non-small cell lung cancer: An interim analysis. Front Immunol. 2022 Aug 19;13:938269. doi: 10.3389/fimmu.2022.938269. eCollection 2022.