Breast Cancer, Carcinoma, Colorectal Cancer, Gastric Cancer, Gynecologic Cancer, Liver Cancer, Lung Cancer, Pancreatic Cancer, Sarcoma
Conditions
Keywords
Oncolytic virus, Herpes simplex virus type 1, Immunotherapy
Brief summary
20 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 advanced solid tumors.
Interventions
R130, a modified herpes simplex virus-Ⅰ (HSV-1) containing the gene coding for anti-CD3 scFv/CD86/PD1/HSV2-US11
Sponsors
The Affiliated Hospital of Xuzhou Medical University
Shanghai Yunying Medical Technology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with solid tumors clearly diagnosed by histology and/or cytology. 2. Failure of standard treatment or patient unwillingness to receive other antitumor therapy. 3. Age 18 to 75 years. 4. Subjects with ECoG score of 0-2. 5. Expected survival of 3 months or more. 6. Have at least one measurable lesion (according to RECIST 1.1 criteria) that is amenable to intratumoral or intraperitoneal drug delivery. 7. Subjects must have appropriate organ function, and laboratory tests during the screening period must meet the following requirements: a) absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets (PLT) ≥ 80 × 109/L, and hemoglobin (Hb) ≥ 85 g/L; b) serum creatinine (Cr) and blood urea nitrogen (BUN) within 1.5 times the upper limit of normal values; c) serum c) serum total bilirubin (TBIL) ≤ 2 times the upper limit of normal values; d) glutamic aminotransferase (ALT) and glutamic oxalacetic aminotransferase (AST) ≤ 2.5 times the upper limit of normal values; subjects with liver metastases do not exceed 5 times the upper limit of normal values; e) activated partial thromboplastin time (APTT), prothrombin time (PT) within 1.5 times the upper limit of normal values. 8. No absolute or relative centasis contraindiction. 9. Eligible patients of childbearing potential must agree to use a reliable method of contraception with their partner for the duration of the trial and for at least 180 days after the last dose; female patients of childbearing potential must have a negative urine pregnancy test within 7 days prior to enrollment. 10. Subjects voluntarily sign an informed consent form and are in good compliance.
Exclusion criteria
1. Have had any serious adverse reactions associated with immunotherapy. 2. 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. 3. Patients with past history of type I diabetes mellitus or HIV. 4. Severe abnormalities in thyroid and cortisol testing; active, known or suspected autoimmune disease requiring systemic therapy. 5. Patients with severe prior interstitial lung changes (as determined by the investigator). 6. Patients with active tuberculosis and a strong positive OT test. 7. Patients with active bleeding or severe coagulation dysfunction. 8. Have had antitumor therapy, including endocrine, chemotherapy, radiotherapy, targeted therapy, immunotherapy and antitumor herbal therapy, 4 weeks prior to the first dose. 9. Have not recovered to CTCAE 4.0 grade rating 0 or 1 level of toxicity after previous antineoplastic therapy. 10. Current active hepatitis B, active hepatitis C, immunodeficiency virus or other active infection of clinical significance. 11. Patients who have undergone surgery of grade 3 or higher or whose surgical wounds have not healed within 4 weeks prior to enrollment. 12. Pregnant, lactating and planning to have children within six months. 13. Subjects who, in the judgment of the investigator, are unsuitable for participation in this trial for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subject incidence of adverse events | Up to 6 months | To characterize the safety profile of R130 injection in patients with advanced solid tumors as measured by the incidence of Grade ≥ 3 Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0) |
| Subject incidence of laboratory abnormalities | Up to 1 month | Detection of liver and renal function, electrocardiogram, routine blood examination etc. |
| Systemic Immune Response | Up to 6 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Assessment for Disease Control Rate | Every 10 weeks for 12 months | Evaluate the efficacy endpoints of DCR by the investigator with RECIST v1.1 and iRECIST |
Other
| Measure | Time frame | Description |
|---|---|---|
| Disease Assessment for Duration of Response | Every 10 weeks for 12 months | Evaluate the efficacy endpoints of DOR by the investigator with RECIST v1.1 and iRECIST |
| Quality of Life Assessment | Every 6 weeks for 12 months | Evaluate with EORTC QLQ-C30 |
Countries
China
Contacts
Primary ContactFeng Pan, MD
Outcome results
None listed