IT or IA Infusion of PD1/PDL1/CTLA4 Inhibitors Versus IV for Immunotherapy of Head/Neck Cancers (HNC)

A Phase II/III Randomized Trial of Comparison of Survival Benefit of Administration of PD1/PDL1/CTLA4 Inhibitors or Their Combinations Via Neck Artery or Intratumor Versus Vein Infusion for Immunotherapy of HNC

This trial was designed to investigate the survival outcomes, response rates, and safety of patients with advanced Head/Neck Squamous cancer via intra-tumor or intra-artery versus vein infusion of PD1/PDL1/CTLA4 inhibitor or their combinations.

Study Overview

• Status: Recruiting
• Conditions: Head/Neck Neoplasm
• Intervention / Treatment: Drug: PD1/PDL1/CTLA4 inhibitors

Detailed Description

Head/Neck cancer is a kind of hard-to-treat malignancy worldwide and its overall survival rate is still low. PD1/PDL1/CTLA4 inhibitors are widely used to treat various of cancers now. Delivery of antibody drugs through interventional approaches including intra-tumor or intra-artery, based on the theory of "first pass effect" of drug, can significantly increase the local drug concentration of the tumor, improve the efficacy, and reduce systemic adverse reactions.

To the investigator's knowledge, no studies have been developed on the survival benefit of neck artery infusion or intra-tumor injection of immunotherapeutic agents in patients with advanced HNC. This phase II-III clinical trial was designed to compare the effects of PD1/PDL1/CTLA4 inhibitor or their combinations via IA/IT and IV on the survival benefit of patients with advanced HNC, including ORR, DCR, median survival time, and safety.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Zhenfeng Zhang, MD, PhD; Phone Number: +862039195966; Email: zhangzhf@gzhmu.edu.cn
• Study Contact Backup: Name: Hui Lian, MD; Phone Number: 02034153532; Email: lian-hui-2008@163.com

Study Locations

• China
  • Guangdong
    • Guanzhou, Guangdong, China, 510260
      • Recruiting
      • The Second Affiliated Hospital of Guangzhou Medical University
      • Contact: Zhenfeng Zhang, MD, PhD; Phone Number: +862039195966; Email: zhangzhf@gzhmu.edu.cn
      • Contact: Hui Lian, MD; Phone Number: 02034153532; Email: lian-hui-2008@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Cytohistological confirmation is required for diagnosis of HNC.
2. Signed informed consent before recruiting.
3. Age between 18 to 80 years with estimated survival over 3 months.
4. ECOG score < 2
5. Tolerable coagulation function or reversible coagulation disorders
6. 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
7. At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.
8. Patients with advanced HNC which would not be suitable for treatment with loco-regional therapies or have progressed following locoregional therapy such as surgical resection and other treatment.
9. Birth control.
10. Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria:

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

5. Patients have poor compliance.

   Any contraindications for neck artery 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).

6. Allergic to adriamycin chemotherapy drugs，contrast agent or lipiodol;
7. Any agents which could affect the absorption or pharmacokinetics of the study drugs
8. Subjects unable to suffer the discomfort of the artery infusion procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD1/PDL1/CTLA4 inhibitor or their combinations infusion via neck artery; Interventional technique is used to localize neck artery to infuse the inhibitor or their combinations directly into tumor.	Drug: PD1/PDL1/CTLA4 inhibitors; Infusion of PD1/PDL1/CTLA4 inhibitors through peripheral vein or neck artery/intra-tumor.
Experimental: PD1/PDL1/CTLA4 inhibitor or their combinations infusion via peripheral vein; Routine peripheral vein infusion of PD1/PDL1/CTLA4 inhibitor or their combinations is performed.	Drug: PD1/PDL1/CTLA4 inhibitors; Infusion of PD1/PDL1/CTLA4 inhibitors through peripheral vein or neck artery/intra-tumor.
Experimental: PD1/PDL1/CTLA4 inhibitor or their combinations infusion via intra-tumor penetration; Interventional technique is used to intra-tumor injection of the inhibitor or their combinations directly into tumor.	Drug: PD1/PDL1/CTLA4 inhibitors; Infusion of PD1/PDL1/CTLA4 inhibitors through peripheral vein or neck artery/intra-tumor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival (PFS) will be defined as the elapsed time from the first date of study treatment until documented disease progression (as per mRECIST) or death from any cause, whichever is earlier. For patients who remain alive without progression, follow-up time will be censored at the date of last disease assessment.	2 years
Adverse event rate	Adverse event rate will be defined as the rate of patients who developed adverse event.	2 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Guangzhou Medical University
• Investigators: Principal Investigator: Zhenfeng Zhang, MD, PhD, Second Affiliated Hospital of Guangzhou Medical University; Principal Investigator: Hui Lian, MD, Second Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2035

Study Registration Dates

• First Submitted: May 13, 2019
• First Submitted That Met QC Criteria: May 14, 2019
• First Posted (Actual): May 16, 2019

Study Record Updates

• Last Update Posted (Actual): June 26, 2024
• Last Update Submitted That Met QC Criteria: June 22, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Interventional therapy; Head/Neck tumor; PD1 antibody; Artery infusion; PDL1 antibody; CTLA4 antibody; Intra-tumor
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors
• Other Study ID Numbers: ZZITICI-009

Drug and device information, study documents

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