A Clinical Study on Oncolytic Virus Injection (R130 OV) for the Treatment of Relapsed/Refractory Head and Neck Cancer

Study Overview
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Brief Summary
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9 participants are expected to be enrolled for this open，single-armed clinical trial to evaluate the safety and efficacy of the recombinant herpes simplex virus Ⅰ, R130 in patients with relapsed/refractory head and neck cancer.

Official Title
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A Clinical Safety and Efficacy Study on Oncolytic Virus Injection (R130) for the Treatment of Relapsed/Refractory Head and Neck Cancer

Conditions
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Head and Neck Cancer, Esophageal Cancer, Otorhinolaryngologic Neoplasms, Ear Cancer, Nose Cancer, Laryngeal Cancer, Pharyngeal Cancer

Intervention / Treatment
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* Drug: Recombinant oncolytic herpes simplex virus type 1 (R130)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with head and neck cancer clearly diagnosed by histology and/or cytology, without systematic metastasis, and failure of standard treatment. Age 18 to 75 years. No absolute or relative centasis contraindiction，have at least one measurable lesion (according to RECIST 1.1 criteria) that is amenable to intratumoral drug delivery. No severe functinonal falure of heart, brain, liver, kidney and lung. Subjects with ECOG score of 0-2, and expected survival of 3 months or more. No evidence of clinically significant immunosuppression. Patients must have the following hematologic parameters, Coagulation functions and hepatic and renal function during the screening period: White Blood Cell (WBC)≥3.0×10^9/L； Absolute Lymphocyte Count (ANC)≥1.5×10^9/L; Platelet≥100×10^9/L； Prothrombin time (PT) or activated Partial Thromboplastin Time（APTT）≤1.5×ULN; Serum Creatinine (Scr)≤1.5×ULN Alanine aminotransferase(AST/ALT) ≤3×ULN; Total Bilirubin(TBIL)≤1.5×ULN. Be able to understand and sign the informed consent document; Be able to stick to follow-up visit plan and other requirements in the agreement. Exclusion Criteria. With a history of allergy to similar drugs. With hematological diseases, malignant tumors of the central nervous system, or combined with other malignant tumors. pregnancy, breast feeding. Current active hepatitis B, active hepatitis C, immunodeficiency virus or other active infection of clinical significance. Impaired function of important organs or a history of organ transplantation. Receiving antiherpes simplex virus therapy such as acyclovir, ganciclovir, vancomycin, and acepromazine within 4 weeks. Have had antitumor therapy, including endocrine, chemotherapy, radiotherapy, targeted therapy, immunotherapy and antitumor herbal therapy,4 weeks prior to the first dose. Have had any serious adverse reactions associated with immunotherapy and have not recovered to CTCAE 5.0 grade rating 0 or 1 level of toxicity after previous antineoplastic therapy. Subjects with any severe and/or uncontrolled disease, including: a) poorly controlled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg); b) suffering from class I or higher myocardial ischemia or myocardial infarction, arrhythmia (QTc ≥ 470 ms and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification); c) active or uncontrolled severe infection (≥ CTCAE grade 2 infection); d) Patients with previous organ transplantation, bone marrow transplantation (hematopoietic stem cell transplantation) and severe immune deficiency; e) Urine routine suggesting urine protein ≥++ and confirmed 24-hour urine protein quantification > 1.0 g. Patients with past history of type I diabetes mellitus. Severe abnormalities in thyroid and cortisol testing; active, known or suspected autoimmune disease requiring systemic therapy. Patients with active bleeding or severe coagulation dysfunction. Researchers considering the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R130 Treatment Group<br>Every 7-14 days,1-2 ml R130 （concentration of 1x10^8 plaque-forming Units/mL,PFU/mL）will be injected intratumoral in patients with relapsed/refractory head and neck cancer | Drug: Recombinant oncolytic herpes simplex virus type 1 (R130)<br>* R130, a modified herpes simplex virus-Ⅰ (HSV-1) containing the gene coding for anti-CD3 scFv/CD86/PD1/HSV2-US11<br>* Other names: Oncolytic virus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Profile Measured by Grade ≥3 CTCAE v5.0 | To characterize the safety profile of R130 injection in patients with relapsed/refractory head and neck cancer as measured by the incidence of Grade ≥ 3 Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0) | Up to 6 months | 
| Systemic immune response | Detection of increased systemic immune Response markers in sera (IL2,IL4,IL6,IL8,IL10,TNFa，IFNγ, etc.) and peripheral blood mononuclear cells by multi-Color fluorescence-activated cell sorting (FACS) | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Assessment for Disease Control Rate | Evaluate the efficacy endpoints of DCR by the investigator with RECIST v1.1 and iRECIST | Every 10 weeks for 12 months | 
| Disease Assessment for Duration of Response | Evaluate the efficacy endpoints of DOR by the investigator with RECIST v1.1 and iRECIST | Every 10 weeks for 12 months | 
| Quality of Life Assessment | Evaluate with EORTC QLQ-C30 | Every 6 weeks for 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncolytic virus, Herpes simplex virus type 1