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

NCT03755739 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ZZITICI-004
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatocarcinoma; Lung Cancer; Melanoma; Renal Cancer; Head and Neck Cancer; Pancreas Cancer; Ovarian Cancer; Colo-rectal Cancer; Cervical Cancer; Breast Cancer

Keywords

Solid cancers; Check-point inhibitors; Interventional Radiology; Trans-artery infusion; Intra-tumor injection

Outcome Measures

Primary Outcomes (2)

• Overall survival

  Overall survival (OS) will be defined as the elapsed time from the enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact (or last date known to be alive). Follow-up for OS will occur every 12 weeks (±1 month) until death or withdrawal of consent from the study.

  5 years

• Complete response (CR) rate before or at Month 6

  Percentage of patients achieving complete response (CR) before or at Month 6

  4

Secondary Outcomes (4)

• Progression-free survival

  5 years

• Duration of remission (DOR)

  5 years

• Disease control rate

  5 years

• Cause of death (COD) when appropriate

  5

Study Arms (2)

Pembrolizumab via localized infusion

EXPERIMENTAL

This group dividied into two subgroups: 1. Checkpoint inhibitor (CPI) such as Pembrolizumab ± Ipilimumab is administrated with a dose of 1-2mg/kg via sustained (10min) micro-pump infusion via artery, plus chemotherapy, every 3 weeks. 2. Checkpoint inhibitor (CPI) such as Pembrolizumab ± Ipilimumab is administrated with a total dose of 150mg via intra-tumor fine needle injection in 5 min, plus doxorubicin, every 3 weeks.

Drug: Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy

Checkpoint inhibitor (CPI) Pembrolizumab plus chemotherapy via vein infusion

ACTIVE COMPARATOR

Checkpoint inhibitor (CPI) such as Pembrolizumab is administrated with a total dose of 2mg/kg via vein infusion (30 min), plus chemotherpy every 3 weeks.

Drug: Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy

Interventions

Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy DRUG

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.

Also known as: Checkpoint inhibitor (CPI) such as Keytruda plus chemotherapy

Checkpoint inhibitor (CPI) Pembrolizumab plus chemotherapy via vein infusion; Pembrolizumab via localized infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Affiliated Hospital of Guangzhou Medical University: lead

Study Sites (1)

The Second Affiliated Hospital of Guangzhou Medical University

Guanzhou, Guangdong, 51260, China

RECRUITING

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Lung Neoplasms; Melanoma; Kidney Neoplasms; Head and Neck Neoplasms; Pancreatic Neoplasms; Ovarian Neoplasms; Colonic Neoplasms; Uterine Cervical Neoplasms; Breast Neoplasms

Interventions

cyclopropapyrroloindole; pembrolizumab; Drug Therapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Gonadal Disorders; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Uterine Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Breast Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Zhenfeng Zhang, MD,PhD

  Second Affiliated Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenfeng Zhang, MD,PhD

CONTACT

02034153532; zhangzhf@gzhmu.edu.cn

Deji Chen, MD,PhD

CONTACT

02034153532; chendeji2003@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2018
• First Posted: November 28, 2018
• Study Start: November 1, 2018
• Primary Completion (Estimated): November 1, 2033
• Study Completion (Estimated): November 1, 2036
• Last Updated: June 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)