Efficacy and Safety of DEB-BACE Combined With PD-1 Inhibitors in Stage II/III NSCLC With Standard Treatment Failure

Efficacy and Safety of DEB-BACE Combined With PD-1 Inhibitors in Stage II/III NSCLC With Standard Treatment Failure: A Prospective, Multicenter, Randomized, Open, Double-arm Clinical Trial

This study is a prospective, multi-center, randomized, open-ended, double-arm clinical study. All eligible patients were randomly assigned to DEB-BACE combined with PD-1 inhibitor (Sindilizumab) treatment group (test group) and DEB-BACE treatment group (control group), to explore the efficacy and safety of combination therapy for stage II/III NSCLC with standard treatment failure or intolerable patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Procedure: Drug-eluting beads bronchial arterial chemoembolization; Drug: Programmed Cell Death Protein 1 Inhibitor

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jianfei Tu, DR.; Phone Number: +8613646782878; Email: jianfei1133@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age more than 18 years old, no gender limit.
• According to the Diagnosis and Treatment of Primary Lung Cancer (2018 edition), non-small cell lung cancer (NSCLC) was diagnosed by histopathology.
• Tumor Node Metastasis (TNM) staging is II-III.
• According to the National Comprehensive Cancer Network (NCCN) guidelines, patients who had failed, refused, or were not suitable for standard treatment (surgery, chemoradiotherapy, targeted) after consultation.
• Eastern Cooperative Oncology Group (ECOG), Performance Status (PS) Score ≤ 2.
• Estimated survival time is more than 3 months.
• The patient has signed informed consent.

Exclusion Criteria:

• The patient has previously received interventional therapy [iodine seed implantation, ablation, bronchial arterial chemoembolization (BACE) therapy], or received immunotherapy during the first-line standard treatment.
• The patient is accompanied by other malignant tumors and had not been cured.
• White blood cell < 3×10*9/L, absolute value of neutrophils < 1.5×10*9/L, neutrophil/lymphocyte ratio ≥ 3, platelet count < 50×10*9/L, hemoglobin concentration < 90 g/L.
• Liver and kidney dysfunction (creatinine > 176.8 μmol/L; aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2 times the upper limit of normal).
• Uncorrectable coagulopathy or active hemoptysis.
• Patient with active infections requires antibiotic treatment.
• Patient has uncontrollable hypertension, diabetes, and cardiovascular disease with obvious symptoms.
• Allergy to contrast agents.
• Women with pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination Treatment Group; Drug-eluting Beads Bronchial Arterial Chemoembolization combined with Programmed Cell Death Protein 1 Inhibitor was used for treatment.	Procedure: Drug-eluting beads bronchial arterial chemoembolization; Drug-eluting beads bronchial arterial chemoembolization generally uses platinum-containing two-drug chemotherapy "platinum (cisplatin, carboplatin, nedaplatin) combined treatment, and drug-loaded microspheres can be loaded with vinorelbine, gemcitabine, irinote Kang, raltitrexed. The dose of chemotherapy drugs is set to 75mg/m2 of platinum, and the dose of chemotherapy through catheter infusion is reduced by 25%. The dose of drug-loaded drugs is vinorelbine 25mg/m2, gemcitabine generally 1000mg/m2, irinotecan 80mg/ m2, raltitrexed 4mg. Chemotherapy was perfused first, followed by embolization with drug-loaded microspheres, until the blood flow in the artery supplying the tumor slowed down and approached stagnation. The number of DEB-BACE treatments is determined by the investigator, and is given as needed according to the patient's condition, usually 1-2 times, with an interval of 28±10 days.; Drug: Programmed Cell Death Protein 1 Inhibitor; Programmed cell death protein 1 inhibitor fixation was treated with sintilimab (Xinda Biopharmaceutical Co., Ltd.). It is administered by intravenous infusion, and the recommended dose is 200 mg, given once every 21 days. The medication will last for two years until disease progression or intolerable toxicity occurs. During immunotherapy, immunosuppressive agents will not be replaced and the dose will not be adjusted.
Active Comparator: Single Treatment Group; Only receive drug-eluting beads bronchial arterial chemoembolization treatment.	Procedure: Drug-eluting beads bronchial arterial chemoembolization; Drug-eluting beads bronchial arterial chemoembolization generally uses platinum-containing two-drug chemotherapy "platinum (cisplatin, carboplatin, nedaplatin) combined treatment, and drug-loaded microspheres can be loaded with vinorelbine, gemcitabine, irinote Kang, raltitrexed. The dose of chemotherapy drugs is set to 75mg/m2 of platinum, and the dose of chemotherapy through catheter infusion is reduced by 25%. The dose of drug-loaded drugs is vinorelbine 25mg/m2, gemcitabine generally 1000mg/m2, irinotecan 80mg/ m2, raltitrexed 4mg. Chemotherapy was perfused first, followed by embolization with drug-loaded microspheres, until the blood flow in the artery supplying the tumor slowed down and approached stagnation. The number of DEB-BACE treatments is determined by the investigator, and is given as needed according to the patient's condition, usually 1-2 times, with an interval of 28±10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	The most common primary endpoint in cancer trials.	The time from enrollment to tumor progression or death from any cause, whichever came first, measured in "months", assessed up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Overall Response	Evaluation index of clinical efficacy of anticancer drugs.	The time from the first assessment of the tumor as complete remission or partial remission to the first assessment as disease progression or death from any cause, assessed up to 12 months.
Overall Survival	The best efficacy endpoint in cancer clinical trials.	Time from randomization to death from any cause, in "months", assessed up to 2 years. For patients who are still alive at the time of data analysis, OS is calculated based on the date when the patient is last known to be alive.
Objective Response Rate	Evaluation index of clinical efficacy of anticancer drugs.	Proportion of patients who achieved complete remission (CR) or partial remission (PR) according to mRECIST criteria, assessed up to 12 months.
Disease Control Rate	Evaluation index of clinical efficacy of anticancer drugs.	Proportion of patients with complete remission (CR), partial remission (PR), and stable disease (SD) according to mRECIST criteria, assessed up to 12 months.
Time to tumor untreatable progression	End point of antitumor drug trial.	The time interval between randomization to tumor progression that patients are unable to further receive treatment, assessed up to 12 months.
Tumor biomarkers	carcinoembryonic antigen, carbohydrate antigen 125, squamous cell carcinoma, etc	From pre-procedure to every follow-up time, assessed up to 2 years.
Eastern Cooperative Oncology Group Score	The patient's performance status score is divided into 6 grades. The lowest grade is 0, and the highest grade is 5. The patient's physical state deteriorates as the grade rises.	From pre-procedure to every follow-up time, assessed up to 2 years.
Recurrence rate of hemoptysis	Hemoptysis occurs again	From date of randomization to every follow-up time, assessed up to 2 years.
Quality of life Questionare-Core score	The European Organization for Reasearch and Treatment of Cancer Quality of life Questionare-Core score. All items and subscales were converted from 0 to 100, with higher scores indicating better overall quality of life.	From date of randomization to every follow-up time, assessed up to 2 years.
The incidence of adverse events and serious adverse events	Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0	From date of randomization to every follow-up time, assessed up to 2 years.
Pain assessment	Visual Analogue Scale/Score.The tool is a 10 cm long roving ruler with 11 scales ranging from 0 to 10. A score of 0 means no pain, and a score of 10 means unbearable pain. The higher the score, the more severe the pain.	From date of randomization to every follow-up time, assessed up to 2 years.

Collaborators and Investigators

• Sponsor: The Central Hospital of Lishui City
• Collaborators: The First Affiliated Hospital of Zhengzhou University; Jiangxi Provincial Cancer Hospital; Zhejiang University; Jiangxi Chest Hospital
• Investigators: Study Director: Xihui Ying, MD., The Central Hospital of Lishui City

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 17, 2021
• First Submitted That Met QC Criteria: February 17, 2022
• First Posted (Actual): February 21, 2022

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: advanced; PD-1 inhibitor; Non-Small-Cell Lung cancer; Drug-eluting Beads Bronchial Arterial Chemoembolization
• 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors
• Other Study ID Numbers: ZJLS-KLDMIR-21002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Statistical analysis plan, informed consent form, and clinical study report can be shared with other researchers.
• IPD Sharing Time Frame: Within six months after the trial is completed.

IPD Sharing Access Criteria

Shared data is not available for downloading, but can only be browsed. To download the data, you must contact the researchers.

Shared data does not provide any private information of the participants.

• IPD Sharing Supporting Information Type: SAP; ICF; CSR

Drug and device information, study documents

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