Clinical trial NCT03952065: IT or IA Infusion of PD1/PDL1/CTLA4 Inhibitors Versus IV for Immunotherapy of Head/Neck Cancers (HNC)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Head/Neck Neoplasm
Keywords: Head/Neck tumor
PD1 antibody
Artery infusion
PDL1 antibody
CTLA4 antibody
Intra-tumor
Interventional therapy
Lead sponsor: Second Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
First posted: 2019-05-16
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 inhibitor or their combinations.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: 2 years
Secondary outcomes:
measure: Progression-free survival
timeFrame: 2 years
measure: Adverse event rate
timeFrame: 2 years
Other outcomes:
Locations:
city: Guanzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: Second Affiliated Hospital of Guangzhou Medical University
name: Hui Lian, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital of Guangzhou Medical University
name: Zhenfeng Zhang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: