Trans-Artery/Intra-Tumor Infusion of Checkpoint Inhibitors Plus Chemodrug for Immunotherapy of Advanced Solid Tumors

Официальное название

A Phase II/III Trial of Comparison of Benefit of Administration of Checkpoint Inhibitors Plus Chemodrug Via Artery or Fine Needle to Tumor Versus Vein for Immunotherapy of Advanced Solid Tumors

Обзор

This trial was designed to investigate the safety, response rates and survival outcomes of patients with advanced solid tumors by trans-artery/intra-tumor infusion of PD1/PDL1 antibody and/or CTLA4 antibody ipilimumab plus chemotherapeutic drug and to compare their differences.

Подробное описание

Malignant solid tumors including lung and liver cancers are the most common malignancy worldwide, and their mortality rates are very high. China has a huge population base, with about 4,000,000 new cases each year. More than 60% of the solid tumors in China are diagnosed at mid-to-late stage and have lost the chance of surgery. Recently a lot of therapeutic strategies have been developed and applied to clinic including targeted therapy and immunotherapy, but the overall efficiency is still low. It is difficult to be widely used in patients with advanced solid cancers, and more alternative therapies are urgently needed.

Antibodies against PD1, PDL1 and CTLA4 are representative drugs for the check-points inhibitory agents, and their clinical indications have been approved in various types of tumors, including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck squamous cell carcinoma patients, et al. Those drugs are regularly systemically administrated by vein infusion, however, local delivery of those drugs via interventional radiology technique including trans-artery or intra-tumor injection may increase the local drug concentration in the tumor, improve the efficacy, and reduce systemic adverse reactions, through so called "first pass effect" of drug on target organs. To the investigator's knowledge, no studies have been developed on the efficacy and survival benefit of localized delivery of checkpoint inhibitors for treatment of cancer patients. This phase II-III clinical trial was designed to compare the effects of Pembrolizumab, Tecentriq, et al and/or ipilimumab plus chemotherapeutic drug such as doxorubicin on the survival benefit of patients with advanced solid cancers, including ORR, DCR, median survival time, and safety.

Вмешательства

• Препарат Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy
  vein, artery, or intra-tumor infusion of checkpoint inhibitor (CPI) such as Pembrolizumab and/or Ipilimumab, plus chemotherapy to destroy cancer cells and release tumor antigen for improving CPI therapeutic efficacy.

Первичные конечные точки

• Overall survival [Срок оценки: 5 years]
• Complete response (CR) rate before or at Month 6 [Срок оценки: 4]

Вторичные конечные точки (4)

• Progression-free survival [Срок оценки: 5 years]
• Duration of remission (DOR) [Срок оценки: 5 years]
• Disease control rate [Срок оценки: 5 years]
• Cause of death (COD) when appropriate [Срок оценки: 5]

Критерии участия

Критерии включения

• Cytohistological confirmation is required for diagnosis of cancer.
• Signed informed consent before recruiting.
• Age above 18 years with estimated survival over 3 months.
• Child-Pugh class A or B/Child score > 7; ECOG score < 2
• Tolerable coagulation function or reversible coagulation disorders
• Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR < 2.3 or PT < 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin > 28 g/L；Total bilirubin < 51 μmol/L
• At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.
• Birth control.
• Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Критерии исключения

• Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
• Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;
• Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
• Patients accompanied with other tumors or past medical history of malignancy;
• Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;
• Patients have poor compliance.

Any contraindications for hepatic arterial infusion procedure:

A.Impaired clotting test (platelet count < 60000/mm3, prothrombin activity < 50%).

B.Renal failure / insufficiency requiring hemo-or peritoneal dialysis. C.Known severe atheromatosis. D.Known uncontrolled blood hypertension (> 160/100 mm/Hg).

• Allergic to contrast agent;
• Any agents which could affect the absorption or pharmacokinetics of the study drugs
• Other conditions that investigator decides not suitable for the trial.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The Second Affiliated Hospital of Guangzhou Medical University — Guanzhou

Публикации

• Tan H, Shah NUH, He B, Liu T, Li T, Liu M, Gu Y, Zhi C, Ou Y, Huang J, Li M, Zuo S, Chen D, Qin R, Yang H, Li X, Lian H, Wu Q, Leidner R, Chen R, Yang A, Yang L, Zhang Z. Intratumoral delivery of PD-1/PD-L1 and CTLA-4 inhibitors for recurrent/refractory solid tumors: a proof-of-concept treatment strategy. Front Immunol. 2025 Dec 12;16:1669924. doi: 10.3389/fimmu.2025.1669924. eCollection 2025. PMID 41459523

Идентификаторы

NCT: NCT03755739 · ZZITICI-004

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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