Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Kezhong Chen, M.D.

Jun Wang, M.D.

To investigate the evolutionary genomic landscape, explore the genetic tumor heterogeneity and microenvironment of multiple primary lung cancer (MPLC) by using tissue genetic analysis and circulating tumor DNA detection, in order to provide robust evidence for the diagnosis, treatment, and surveillance of MPLC.

Multiple primary lung cancer (MPLC) has become a worldwide problem due to the difficulty in diagnosis, treatment and surveillance. Although exploring tumour clonal heterogeneity and microenvironment can help understand cancer evolution and impact therapeutic outcome, study is still lacking in this field on MPLC. Circulating tumor DNA (ctDNA) are short DNA fragments, which can be obtained conveniently and non-invasively, providing comprehensive views of the tumor as were shed by tumor cells from multiple tumor regions. Therefore, we design a prospective study of patients with surgically treated MPLC, aiming to use ctDNA technique to define the evolutionary landscape of MPLC through inter-tumor and intra-tumor heterogeneity by multi-region sampling and genetic analysis. We will also explore the the microenvironment by RNA sequencing and T cell receptor sequencing. This study may help understand the genetic evolution and microenvironment of MPLC, and provide evidence for the diagnosis, treatment and surveillance of these patients.

Fresh tumor tissue and blood samples were collected from each patient. Time for blood sample collection: 1) Preoperation. 2) The 1st to 3rd day of postoperation.

Evolution of Multiple Primary Lung Cancer (Evolution)

The Genetic Evolution and Microenvironment of Multiple Primary Lung Cancer

Explore the intra-tumor and inter-tumor genetic heterogeneity by analysis of clonal and subclonal mutations detected by ctDNA.

Using RNA sequencing and T cell receptor (TCR) sequencing to evaluate the microenvironment of each lesion of multiple primary lung cancer, including T cell receptpr clonality ,diversity , evenness, and richness.

Explore the correlation between the detection rate of ctDNA and subclonal mutations of different tumor sites detected by genetic analysis.

Explore the correlation between the detection rate of ctDNA and tumor burden.

Guangzhou Burning Rock Medical Examination Institute Co., Ltd.

Peking University People's Hospital

All Drugs and Chemicals

Central Nervous System Depressants

Other Dietary Supplements

Imidacloprid

Benzocaine

Aflutinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tannic Acid

After randomization, the enrolled patients in this arm should be completely free from the risk of perioperative complications or recovered from the effects of complications, usually no earlier than 4 weeks after surgery but no more than 10 weeks after surgery, before receiving baseline follow-up and starting oral administration of Furmonertinib on the day of baseline follow-up. Patients in the treatment group should take Furmonertinib (80 mg each time) orally on an empty stomach before breakfast once a day. The medicine should be taken about the same time each day, by swallowing the whole tablet with water, without crushing or chewing. Patients should maintain oral administration of Furmonertinib for 6 consecutive months, unless there is disease progression, death, new anti-tumor therapy received or intolerance of investigational drugs.

After randomization, the enrolled patients in this arm should be completely free from the risk of perioperative complications or recovered from the effects of complications, usually no earlier than 4 weeks after surgery but no more than 10 weeks after surgery, before receiving baseline follow-up and starting oral administration of placebo on the day of baseline follow-up. Patients in the treatment group should take placebo (80 mg each time) orally on an empty stomach before breakfast once a day. The medicine should be taken about the same time each day, by swallowing the whole tablet with water, without crushing or chewing. Patients should maintain oral administration of placebo for 6 consecutive months, unless there is disease progression, death, new anti-tumor therapy received or intolerance of investigational drugs.

AST2818 is an irreversible and highly selective EGFR inhibitor independently discovered and developed by Allist. It has the potential to become the best-in-class drug in the third-generation EGFR-TKIs. Data from the preclinical studies and the completed clinical studies show that AST2818 has the following advantages: 1) AST2818 has good target selectivity and tissue distribution specificity; 2) The objective response rate of AST2818 for the patients with locally advanced or metastatic NSCLC with EGFR T790M mutation is outstanding, reaching 74.1% in the key registration clinical study; 3) AST2818 has a good safety profile and is well-tolerated; 4) AST2818 and its active metabolites have a superior ability to penetrate the blood-brain barrier, and have a good therapeutic efficacy on brain metastases frequently seen in patients with NSCLC.

furmonertinib

The placebo has the same appearance, weight, and physical and chemical properties as the study drug, and is provided by the researcher to the subjects in control group.

Placebo

Hecheng Li, PhD, MD

Yajia Zhang, PhD, MD

Chun Chen, Phd, MD

Bentong Yu, PhD, MD

Xiaolong Yan

Yajie Zhang, PhD, MD

Jiahao Zhang, MD

Ming Wu, Phd, MD

Jian Hu, PhD, MD

This study is a multi-center, prospective, double-blind randomized controlled clinical trial. The purpose is to evaluate the efficacy and safety of EGFR-TKI on residual GGOs after surgery in patients with multiple primary lung cancers with ground glass nodules. This study is expected to prove that compared with placebo in the control group, EGFR-TKI can significantly reduce the residual GGOs lesions in patients with EGFR-positive multiple primary lung cancers with ground-glass opacity, and bring a higher objective response rate (ORR), thus provides new insights for treatment of these patients.

Lung cancer is one of the most deadly malignant tumors in the world. It is estimated that 0.2-20% of lung cancer patients have multiple primary lung cancers at the time of diagnosis, and many of them present with multiple ground glass opacities. The surgical method for such multiple lesions depends on their number, anatomical location and size, as well as the age and pulmonary function of the patient. It is easily affected by the subjective judgment of the surgeon. Besides, many of these patients develop multiple lesions that cannot be resected at the same time, and there haven't been established a standard therapy for residual GGO lesions after surgery.

According to the National Comprehensive Cancer Network (NCCN) guidelines, EGFR-TKI is recommended for the adjuvant treatment of stage IB-ⅢA NSCLC with EGFR mutations. However, it is not clear whether EGFR-TKI is effective for multiple primary lung cancers or the residual GGOs after surgical resection of the EGFR mutation positive main cancers. At present, there have been retrospective studies showing that application of EGFR-TKIs targeted therapy can significantly reduce the diameter of residual GGOs after surgery resection of EGFR mutation-positive primary lesions for MPLC patients, and reduce the secondary surgery caused by the progression of the lesion. However, there is no prospective Studies confirming the efficacy and safety of EGFR-TKI on these postoperative residual GGOs lesions.

This study is a multi-center, prospective, double-blind, comparative clinical research. This study plans to enroll 138 patients with multiple primary lung cancers (cTis-T1c, N0, M0) that manifest GGO and cannot be resected at the same time, patients should have undergone surgical resection of the EGFR mutated main lesion, and have no less than 1 GGO lesion remaining after surgery. Eligible patients will be randomly divided into the treatment group (receiving furmonertinib mesilate tablets) or control group (placebo) at a ratio of 1:1. The grouping process was strictly double-blind for both the investigators and subjects. By collecting the relevant data of patients' baseline images, pathology, and follow-up images during treatment, statistical analysis is used to evaluate the effectiveness (response rate, objective remission rate), safety, and relevant influencing factors (including CTR value of the main lesion, number of residual lesions, diameter of the largest residual lesion, higher stage of the main lesion, residual lesion's density, etc.) of EGFR-TKI treatment.

This study is expected to prove that compared with the placebo in the control group, EGFR-TKI can significantly reduce the diameter of residual GGO lesions in patients with EGFR-positive multiple primary lung cancers with ground-glass density, and bring a higher objective response rate (ORR) but did not significantly increase the incidence of adverse effects.

This study has two parallel arms, EGFR-TKI treatment arm and control arm (placebo) are included in this study.

This study is a double-blind trial, the investigator, care provider and patients are all blinded.

Treatment of EGFR-TKI for Residual Lesions of Multiple Synchronous Ground-glass Opacities

A Prospective, Multi-center, Double-blind Randomized Controlled Clinical Trial on the Treatment of EGFR-TKI for Residual Lesions of Multiple Synchronous Ground-glass Opacities

defined in this study as the ratio of patients with reduced diameter of any residual lesions on CT scans to the entire patient cohort according to the Independent Review Committee (IRC) image evaluation follow-up.

Defined as the ratio of lesions showing any reduction in diameter on the CT scan to the number of lesions in the entire cohort according to the Independent Review Committee (IRC) image evaluation during follow-up.

ORR is evaluated after 6 months of treatment, defined according to the RECIST1.1 standard

compared with the primary endpoint of Independent Review Committee (IRC) image evaluation

Number of subjects who had a second resection of residual lesions due to progress of lesions during follow-up.

the number and grades of treatment-related adverse events in each arm (grading according to CTCAE 5.0)

Fujian Medical University Union Hospital

First Affiliated Hospital of Zhejiang University

Second Affiliated Hospital, School of Medicine, Zhejiang University

Tang-Du Hospital

The First Affiliated Hospital of Nanchang University

Ruijin Hospital

Professor

Antibodies

Immunoglobulins

Immunologic Factors

Patients receive the treatment of PD-1 antibody Sintilimab

Patients in experimental group receive the treatment of PD-1 antibody Sintilimab

PD-1 antibody Sintilimab

Jianxing He, MD

Wenhua Liang, PhD

A single-center,prospective interventional study to explore the efficacy of PD-1 antibody Sintilimab on early-stage multiple primary lung cancer patients with ground-glass nodules in CT scan.

This study is a single-center,prospective interventional clinical study, all subjects enrolled are multiple primary lung cancer patients with ground-glass density in CT scan.The samples plan for the study was 36 cases.The enrolled patients will receive intravenous infusion of Sintilimab 200mg every 3 weeks up to 4 cycles, and the efficacy will be evaluated after cycle 2 and 4 using RECIST criteria (version 1.1 ).

The Efficacy of PD-1 Antibody Sintilimab on Early-stage Multiple Primary Lung Cancer With Ground Glass Density.

The Efficacy of PD-1 Antibody Sintilimab on Early-stage Multiple Primary Lung Cancer With Ground Glass Density: A Prospective Interventional Two-stage Simon Design Phase II Study.

The objective response rate will be evaluated after 4 courses of treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evolution of Multiple Primary Lung Cancer (Evolution)	NCT04326751	Multiple Primar... Lung Cancer Non Small Cell ...		18 Years - 80 Years	Peking University People's Hospital
Treatment of EGFR-TKI for Residual Lesions of Multiple Synchronous Ground-glass Opacities	NCT04982900	Multiple Primar...	furmonertinib Placebo	18 Years - 80 Years	Ruijin Hospital
The Efficacy of PD-1 Antibody Sintilimab on Early-stage Multiple Primary Lung Cancer With Ground Glass Density.	NCT04026841	Multiple Primar...	PD-1 antibody S...	18 Years -	The First Affiliated Hospital of Guangzhou Medical University

Spots Global Cancer Trial Database for multiple primary lung cancers