Bronchial Artery Chemoembolization (BACE) Combination Therapy for Advanced NSCLC

Официальное название

A Single-Arm Phase II Study of Bronchial Artery Chemoembolization (BACE) Combination Therapy in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Without Standard Treatment Options

Обзор

Patients with advanced non-small cell lung cancer (NSCLC) who experience disease progression after standard systemic therapies or are unable to tolerate such therapies have limited subsequent treatment options. Bronchial arterial chemoembolization (BACE) is a locoregional interventional procedure that delivers chemotherapeutic agents directly into tumor-feeding bronchial arteries, followed by arterial embolization, with the aim of increasing local drug exposure and reducing tumor blood supply. This prospective, open-label, single-arm Phase II study will evaluate the efficacy and safety of BACE-based combination therapy in adult patients with advanced NSCLC who have no remaining standard treatment options and whose target intrathoracic lesions are considered suitable for BACE. Approximately 20 eligible participants are planned for enrollment between April 2026 and April 2028. All enrolled participants will receive protocol-specified BACE in combination with systemic anti-tumor therapy. Treatment selection and administration will be performed according to the study protocol, taking into account the participant's molecular characteristics, prior treatments, clinical condition, and treatment tolerance. The study will primarily assess local tumor control and the safety of the combined treatment strategy. Tumor response and disease progression will be evaluated by contrast-enhanced imaging according to RECIST criteria, and adverse events will be assessed using CTCAE Version 5.0. Additional assessments will include objective tumor response, disease control, progression-free survival, and overall survival. Exploratory analyses will investigate the systemic pharmacokinetics of chemotherapeutic agents administered during BACE and potential treatment-related changes in the tumor immune microenvironment.

Подробное описание

This prospective, open-label, single-arm Phase II study is designed to investigate BACE-based combination therapy in patients with advanced non-small cell lung cancer who have exhausted, progressed after, or are unable to tolerate available standard systemic treatments. The study focuses on patients with clinically relevant intrathoracic tumor lesions that remain technically suitable for bronchial arterial intervention.

BACE is intended to provide concentrated locoregional treatment to lung tumors through the bronchial arterial circulation. During the procedure, tumor-feeding bronchial arteries will be identified by angiography and selectively catheterized in accordance with the protocol. Protocol-specified chemotherapeutic agents will then be administered through the target arteries, followed by embolization of the tumor-feeding vessels. This approach is intended to increase drug exposure within the tumor while reducing arterial blood supply and inducing tumor ischemia and necrosis.

BACE will be administered in combination with protocol-defined systemic anti-tumor treatment. The systemic treatment include chemotherapy, immune checkpoint inhibition, targeted therapy, or another protocol-permitted regimen, as appropriate for the participant's tumor molecular profile, previous treatment history, organ function, clinical condition, and prior treatment tolerance. The timing and administration of systemic therapy in relation to BACE will follow the study protocol. There is no control group or placebo treatment in this study.

Before treatment, participants will undergo protocol-specified baseline clinical, laboratory, and imaging assessments. Contrast-enhanced chest computed tomography will be used to document measurable intrathoracic lesions and establish the baseline tumor burden. Follow-up imaging will be performed at protocol-defined intervals to evaluate changes in target lung lesions and overall disease status according to RECIST criteria. Local progression of the treated intrathoracic lesions will be distinguished from progression occurring at other pulmonary or extrapulmonary sites.

Safety monitoring will cover both procedure-related complications and toxicities associated with the combined systemic treatment. Clinical symptoms, laboratory abnormalities, imaging findings, and adverse events will be evaluated throughout treatment and during the protocol-defined safety follow-up period. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. Investigators will assess the relationship of each adverse event to BACE, embolization, intra-arterial chemotherapy, and concomitant systemic anti-tumor therapy.

Participants will be followed for local tumor status, overall disease progression, subsequent anti-tumor treatments, and survival. The study is intended to determine whether BACE-based combination therapy can provide clinically meaningful local tumor control with an acceptable safety profile in this heavily pretreated population.

The study also includes exploratory pharmacokinetic and translational research. Peripheral venous blood samples will be collected at protocol-defined time points within 72 hours after BACE to characterize the systemic exposure to chemotherapeutic agents administered through the bronchial arteries. Serial biospecimens collected at baseline, before BACE, and during follow-up will be used to investigate treatment-related changes in local and systemic immune status. These analyses will explore whether ischemia, tumor necrosis, and locoregional drug delivery induced by BACE are associated with changes in the tumor immune microenvironment and whether potential immune biomarkers correlate with treatment response or prognosis.

Time-to-event variables will be summarized using Kaplan-Meier methods. Tumor response proportions will be reported with exact two-sided confidence intervals, and safety findings will be summarized descriptively. Pharmacokinetic and biomarker analyses are exploratory and will primarily use descriptive methods without formal confirmatory hypothesis testing.

Вмешательства

• Процедура Bronchial Arterial Chemoembolization (BACE)
  Interventional chemoembolization procedure targeting tumor-feeding bronchial arteries for local tumor control.
• Препарат Systemic anti-tumor combination medications
  Systemic chemotherapy, immune checkpoint inhibitors or targeted agents administered in combination with BACE procedure per protocol，the BACE regimen was planned for 2 cycles

Первичные конечные точки

• Local Time to Progression (Local TTP) of target intrathoracic lesions [Срок оценки: Up to 24 months after the first BACE treatment]
• Incidence and severity of treatment-related adverse events (TRAEs) [Срок оценки: From the first BACE procedure until 30 days after the last study treatment]

Вторичные конечные точки (4)

• Objective Response Rate (ORR) [Срок оценки: Up to 24 months after initial BACE treatment]
• Disease Control Rate (DCR) [Срок оценки: Up to 24 months after initial BACE treatment]
• Progression-Free Survival (PFS) [Срок оценки: Up to 36 months after enrollment]
• Overall Survival (OS) [Срок оценки: Up to 36 months after enrollment]

Критерии участия

Критерии включения

• Age between 18 and 75 years old; Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2.
• Histopathologically confirmed advanced non-small cell lung cancer (NSCLC), with at least one measurable target lesion defined by RECIST Version 1.1.
• Two eligible patient subgroups:

Patients with negative driver gene alterations: experienced disease progression or intolerable toxicity after platinum-based doublet chemotherapy combined with PD-1/PD-L1 immune checkpoint inhibitors; Patients with positive driver gene mutations (e.g., EGFR, ALK): experienced disease progression or unacceptable adverse reactions after corresponding targeted therapy plus at least one line of systemic chemotherapy.

• Target lung lesions are suitable for bronchial arterial chemoembolization (BACE), as assessed by interventional radiology specialists.
• Adequate function of major vital organs.
• Able to provide written informed consent prior to any study-related procedures.

Критерии исключения

• Histopathological confirmation of mixed small cell lung cancer components.
• Active bleeding or coagulation disorders.
• Severe hypersensitivity to contrast media, chemotherapeutic agents, or combined study medications.
• Extensive and rapidly progressive intra-pulmonary or extra-pulmonary metastatic lesions.
• Angiography during the procedure shows that superselective catheterization cannot completely avoid hazardous blood vessels such as spinal arteries.
• Severe pre-existing hepatic, renal, cardiac, or pulmonary dysfunction.
• Estimated survival time less than 3 months.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fujian Cancer Hospital — Фучжоу

Публикации

• Cui W, Li J, Tian J, Deng Y, Chen J, Cui J, Wang Q, Mai Q, Chen X, Zhang J, Xu R. Drug-eluting beads bronchial arterial chemoembolization in advanced and standard treatment-refractory/ineligible non-small cell lung cancer. Quant Imaging Med Surg. 2025 Apr 1;15(4):3458-3468. doi: 10.21037/qims-24-1789. Epub 2025 Mar 28. PMID 40235787
• Zhao YW, Liu S, Qin H, Sun JB, Su M, Yu GJ, Zhou J, Gao F, Wang RY, Zhao T, Zhao GS. Efficacy and safety of CalliSpheres drug-eluting beads for bronchial arterial chemoembolization for refractory non-small-cell lung cancer and its impact on quality of life: A multicenter prospective study. Front Oncol. 2023 Apr 14;13:1110917. doi: 10.3389/fonc.2023.1110917. eCollection 2023. PMID 37124525
• Shang B, Li J, Wang X, Li D, Liang B, Wang Y, Han X, Dou W, Chen G, Shang J, Jiang S. Clinical effect of bronchial arterial infusion chemotherapy and CalliSpheres drug-eluting beads in patients with stage II-IV lung cancer: A prospective cohort study. Thorac Cancer. 2020 Aug;11(8):2155-2162. doi: 10.1111/1759-7714.13522. Epub 2020 Jun 30. PMID 32603550
• Zhang F, Liu Y. Clinical study on bronchial artery chemoembolization for unresectable non-small cell lung cancer. Front Oncol. 2025 Sep 3;15:1591752. doi: 10.3389/fonc.2025.1591752. eCollection 2025. PMID 40969256
• Liu Y, Zhang X, Zhang F, Song W. Bronchial artery chemoembolization in the treatment of refractory central lung cancer with atelectasis. Front Oncol. 2024 Jun 12;14:1343324. doi: 10.3389/fonc.2024.1343324. eCollection 2024. PMID 38933450
• Zhang F, Liu Y. Transcatheter arterial chemoembolization for lung malignant tumors. Front Oncol. 2025 Apr 16;15:1551644. doi: 10.3389/fonc.2025.1551644. eCollection 2025. PMID 40308513
• Xiang Y, Liu X, Wang Y, Zheng D, Meng Q, Jiang L, Yang S, Zhang S, Zhang X, Liu Y, Wang B. Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges. Front Immunol. 2024 Apr 9;15:1366260. doi: 10.3389/fimmu.2024.1366260. eCollection 2024. PMID 38655260
• Koban MU, Hartmann M, Amexis G, Franco P, Huggins L, Shah I, Karachaliou N. Targeted Therapies, Novel Antibodies, and Immunotherapies in Advanced Non-Small Cell Lung Cancer: Clinical Evidence and Drug Approval Patterns. Clin Cancer Res. 2024 Nov 1;30(21):4822-4833. doi: 10.1158/1078-0432.CCR-24-0741. PMID 39177967

Идентификаторы

NCT: NCT07738367 · K2026-125

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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