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

Second Affiliated Hospital of Guangzhou Medical University

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Head/Neck Neoplasm

Treatments: Drug: PD1/PDL1/CTLA4 inhibitors

Study type: Interventional

Funder types: Other

Identifiers

NCT03952065

ZZITICI-009

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 3 patient groups

PD1/PDL1/CTLA4 inhibitor or their combinations infusion via neck artery

Experimental group

Description:

Interventional technique is used to localize neck artery to infuse the inhibitor or their combinations directly into tumor.

Treatment:

Drug: PD1/PDL1/CTLA4 inhibitors

PD1/PDL1/CTLA4 inhibitor or their combinations infusion via peripheral vein

Experimental group

Description:

Routine peripheral vein infusion of PD1/PDL1/CTLA4 inhibitor or their combinations is performed.

Treatment:

Drug: PD1/PDL1/CTLA4 inhibitors

PD1/PDL1/CTLA4 inhibitor or their combinations infusion via intra-tumor penetration

Experimental group

Description:

Interventional technique is used to intra-tumor injection of the inhibitor or their combinations directly into tumor.

Treatment:

Drug: PD1/PDL1/CTLA4 inhibitors