Neoadjuvant Therapy in Resectable Non-Small Cell Lung Cancer Stages IIB-IIIB

An Open, Observational Clinical Study, 2-3 Cycles Treatment as Neoadjuvant Therapy for NSCLC With Stage IIB-IIIB

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）

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: anti-PD-1 or anti-PD-L1; Drug: EGFR-TKI, ALK inhibitor, ROS1 inhibitor; Drug: investigator decided

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

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Shun D Lu; Phone Number: 15216769608 86-21-62821990; Email: shunlu@sjtu.edu.cn
• Study Contact Backup: Name: Yaxian Yao; Phone Number: 15216769608; Email: yaxianyao@hotmail.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Oncology Department, Shanghai Chest Hospital
    • Contact: Yaxian Yao; Phone Number: 15216769608

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

NSCLC participants in stage IIB-IIIB(American Joint Committee on Cancer 8th edition criteria)

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Neoadjuvant immunotherapy; pd-1 or pd-l1 inhabitors	Drug: anti-PD-1 or anti-PD-L1; immunotherapy anti-PD-1 or anti-PD-L1; Other Names: Neoadjuvant immunotherapy
Neoadjuvant targeted therapy; TKIs	Drug: EGFR-TKI, ALK inhibitor, ROS1 inhibitor; targeted therapy EGFR-TKI, ALK inhibitor, ROS1 inhibitor; Other Names: Neoadjuvant targeted therapy
Neoadjuvant chemotherapy; chemotherapy	Drug: investigator decided; chemotherapy; Other Names: Neoadjuvant chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS: disease free survival	The time length from randomization(mainly from the receipt of pathology and genetic diagnosis reports)to any of the following events: disease progression, disease recurrence or death from any cause. Disease progression or relapse will be assessed according to RECIST 1.1	36 months
pCR: pathologic complete response	the proportion of patients achieved pathologic complete response（lung and lymph node without tumor residual assessed by pathology review)	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS: Overall survival	The time length from the date of randomization (according to the received pathology and genetic diagnosis report) to the date of death.	36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
cRR rates	The proportion of patients achieved complete or patial remission(Imageological) according to RECIST 1.1 prior to definitive surgery	approximately 10 weeks After surgery
Safty AEs	proportion of delayed or cancelled surgery or duration of surgery or length of hospitalization or surgical procedure, and incidence of AE/SAE associated with surgery, Adverse events will be graded according to NCI CTCAE	36 months
Qol Quality of Life	Quality of life asscesed by Quality of Life Questionnare-Core 30(EORTC QLQ-C30）of The European O-rganization for Reasearch and Treatment of Cancer containing 30 items in total. Among them, items 29 and 30 are divided into seven grades. According to the answer options 1 to 7 points. Other items are divided into four grades: none, one point, some to many. When scoring, they are directly rated 1 to 4 points. For functional and overal health domain, higher score means better life quality; for symptom domain ,higher score means worse life quality.	36 months

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital
• Investigators: Study Chair: Shun Lu, Shanghai Chest Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: April 27, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 12, 2019

Study Record Updates

• Last Update Posted (Actual): July 29, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: Neoadjuvant study of NSCLC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No