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

Head/Neck Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03952065
• Other study ID #: ZZITICI-009
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: January 1, 2019
• Est. completion date: January 1, 2029

Study information

• Verified date: December 2023
• Source: Second Affiliated Hospital of Guangzhou Medical University
• Contact: Hui Lian, MD
• Phone: 02034153532
• Email: lian-hui-2008[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 inhibitors.

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 inhibitors via IA/IT and IV on the survival benefit of patients with advanced HNC, including ORR, DCR, median survival time, and safety.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 1, 2029
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Neoplasms
• Head/Neck Neoplasm

Intervention

Drug:
• PD1/PDL1/CTLA4 inhibitors
Infusion of PD1/PDL1/CTLA4 inhibitors through peripheral vein or neck artery/intra-tumor.

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Guangzhou Medical University	Guanzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital of Guangzhou Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Adverse event rate	Adverse event rate will be defined as the rate of patients who developed adverse event.	2 years