Multicenter Observational Study of Advanced Non-small Cell Lung Cancer With Malignant Pleural Effusion

Multicenter Observational Study for Correlation Between Tumor Mutation Burden and Immunotherapy Efficacy of Advanced Non-small Cell Lung Cancer With Malignant Pleural Effusion

Multicenter observational study for correlation between tumor mutation burden and immunotherapy efficacy of advanced non-small cell lung cancer with malignant pleural effusion

Study Overview

• Status: Unknown
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Other: Non-Intervention

Detailed Description

Method of Research:

1. ⅢB-Ⅳ NSCLC patients, tumor mutation burden (TMB) was tested by the 448 gene panel with pleural effusion and tissue sample, to observed mutation characteristics;Tissue and pleural effusion cell precipitation:TMB (Next generation sequencing, 448 gene panel;Average sequencing depth: above 5000×)
2. The date of blood routine examination(neutrophils to lymphocytes ratio (NLR)) and serological tumor maker of NSCLC were collected before treatment;the The results of Programmed death ligand 1 (PDL1) expression level were collected also;
3. Collected Imaging(CT)and pathological data before treatment;
4. Immunotherapy was applied for 8 weeks to evaluate the efficacy;
5. The tumor mutation burden of pleural effusion was tested again for the patients of hyper-progression after immunotherapy, the mutation characteristics and changes were observed, the molecular mutation change before and after treatment were evaluated, and the correlation with immunotherapy was analyzed.Hyper-progression (HPD) were defined as tumor growth rate excess of 50% compared to baseline CT scans prior to treatment initiation.The patient underwent imaging examination (chest CT or pet-ct) at 2 months (8 weeks) after 3 full doses of immunotherapy drugs.
6. The date of blood routine examination(neutrophils to lymphocytes ratio (NLR)) and serological tumor maker of NSCLC were collected after treatment;
7. Imaging, CT and pathological data of patients after treatment were collected

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Chengzhi Zhou; Phone Number: 020-83062830; Email: doctorzcz@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Histologically or cytologically proven diagnosis of ⅢB-Ⅳ NSCLC

Description

Inclusion Criteria:

1. male or female,18 years ≤ age ≤80 years;
2. Pathologically confirmed stage ⅢB-Ⅳ NSCLC, which is not suitable for surgical resection;
3. No systematic anti-tumor treatment;
4. Pleural effusion ≥50ml,tissue samples can be obtained;
5. The driver gene was negative, and immunotherapy was proposed;
6. According to RECIST 1.1, at least one tumor lesion that can be measured or evaluated;
7. Signed and dated informed consent

Exclusion Criteria:

1. No pathological diagnosis or the diagnosis is not clear;
2. Severe pneumonia or tuberculosis;
3. Tumor tissues cannot be obtained;
4. Combine with other tumor type or other subtypes of lung cancer;
5. Poor compliance, unable to complete follow-up;
6. The investigator judges the situation that may affect the clinical search process and results

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Immunotherapy effective; Immunotherapy was applied for 8 weeks to evaluate the efficacy，The efficacy of immunotherapy was evaluated by imaging, and was evaluated according to RECIST 1.1.	Other: Non-Intervention; Non-Intervention
Immunotherapy Ineffective; Immunotherapy was applied for 8 weeks to evaluate the efficacy，The efficacy of immunotherapy was evaluated by imaging, and was evaluated according to RECIST 1.1.	Other: Non-Intervention; Non-Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) of NSCLC patients with malignant pleural effusion who were received immunotherapy	The relationship between tumor mutation burden and objective response rate in NSCLC patients	2021
Progression-free survival (PFS) of NSCLC patients with malignant pleural effusion who were received immunotherapy	The relationship between tumor mutation burden and progression-free survival in NSCLC patients	2021
Overall survival (OS) of NSCLC patients with malignant pleural effusion who were received immunotherapy	The relationship between tumor mutation burden and overall survival in NSCLC patients	2022

Collaborators and Investigators

• Sponsor: Guangzhou Institute of Respiratory Disease

Publications and helpful links

General Publications

• Gandara DR, Paul SM, Kowanetz M, Schleifman E, Zou W, Li Y, Rittmeyer A, Fehrenbacher L, Otto G, Malboeuf C, Lieber DS, Lipson D, Silterra J, Amler L, Riehl T, Cummings CA, Hegde PS, Sandler A, Ballinger M, Fabrizio D, Mok T, Shames DS. Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nat Med. 2018 Sep;24(9):1441-1448. doi: 10.1038/s41591-018-0134-3. Epub 2018 Aug 6.
• Qin BD, Jiao XD, Zang YS. Tumor mutation burden to tumor burden ratio and prediction of clinical benefit of anti-PD-1/PD-L1 immunotherapy. Med Hypotheses. 2018 Jul;116:111-113. doi: 10.1016/j.mehy.2018.05.005. Epub 2018 May 16.
• Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, Kaley TJ, Kendall SM, Motzer RJ, Hakimi AA, Voss MH, Russo P, Rosenberg J, Iyer G, Bochner BH, Bajorin DF, Al-Ahmadie HA, Chaft JE, Rudin CM, Riely GJ, Baxi S, Ho AL, Wong RJ, Pfister DG, Wolchok JD, Barker CA, Gutin PH, Brennan CW, Tabar V, Mellinghoff IK, DeAngelis LM, Ariyan CE, Lee N, Tap WD, Gounder MM, D'Angelo SP, Saltz L, Stadler ZK, Scher HI, Baselga J, Razavi P, Klebanoff CA, Yaeger R, Segal NH, Ku GY, DeMatteo RP, Ladanyi M, Rizvi NA, Berger MF, Riaz N, Solit DB, Chan TA, Morris LGT. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019 Feb;51(2):202-206. doi: 10.1038/s41588-018-0312-8. Epub 2019 Jan 14.
• Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, Schrock A, Campbell B, Shlien A, Chmielecki J, Huang F, He Y, Sun J, Tabori U, Kennedy M, Lieber DS, Roels S, White J, Otto GA, Ross JS, Garraway L, Miller VA, Stephens PJ, Frampton GM. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017 Apr 19;9(1):34. doi: 10.1186/s13073-017-0424-2.
• Wang Z, Duan J, Cai S, Han M, Dong H, Zhao J, Zhu B, Wang S, Zhuo M, Sun J, Wang Q, Bai H, Han J, Tian Y, Lu J, Xu T, Zhao X, Wang G, Cao X, Li F, Wang D, Chen Y, Bai Y, Zhao J, Zhao Z, Zhang Y, Xiong L, He J, Gao S, Wang J. Assessment of Blood Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Patients With Non-Small Cell Lung Cancer With Use of a Next-Generation Sequencing Cancer Gene Panel. JAMA Oncol. 2019 May 1;5(5):696-702. doi: 10.1001/jamaoncol.2018.7098.
• Yarchoan M, Hopkins A, Jaffee EM. Tumor Mutational Burden and Response Rate to PD-1 Inhibition. N Engl J Med. 2017 Dec 21;377(25):2500-2501. doi: 10.1056/NEJMc1713444. No abstract available.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2020
• Primary Completion (ANTICIPATED): March 1, 2021
• Study Completion (ANTICIPATED): March 1, 2022

Study Registration Dates

• First Submitted: February 7, 2020
• First Submitted That Met QC Criteria: February 7, 2020
• First Posted (ACTUAL): February 11, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: immunotherapy; Pleural effusion; Multicenter Observational Study; Tumor Mutation Burden (TMB)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pleural Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Pleural Effusion, Malignant; Pleural Effusion
• Other Study ID Numbers: LC-IMMA

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