A Clinical Study on Oncolytic Virus Injection (R130) for the Treatment of Relapsed/Refractory Advanced Solid Tumors
Study Details
Study Description
Brief Summary
24 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 advanced solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: R130 Treatment Group Every 7-14 days,1-4 ml R130 （concentration of 1x10^8 plaque-forming Units/mL,PFU/mL）will be injected intratumoral or intraperitoneal in patients with advanced solid tumors |
Drug: Recombinant oncolytic herpes simplex virus type 1 (R130)
R130, a modified herpes simplex virus-Ⅰ (HSV-1) containing the gene coding for anti-CD3 scFv/CD86/PD1/HSV2-US11
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients with advanced solid tumors clearly diagnosed by histology and/or cytology.
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Failure of standard treatment or patient unwillingness to receive other antitumor therapy.
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Age 18 to 75 years.
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Subjects with ECOG score of 0-2.
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Expected survival of 3 months or more.
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Have at least one measurable lesion (according to RECIST 1.1 criteria) that is amenable to intratumoral or intraperitoneal drug delivery.
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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.
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Any treatment for malignancy, including radiotherapy, chemotherapy and biological agents, must be discontinued 28 days prior to R130 treatment.
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Eligible patients of childbearing potential must agree to use a reliable method of contraception (hormonal or barrier method or abstinence) 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.
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Subjects voluntarily sign an informed consent form and are in good compliance.
Exclusion Criteria:
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Have had any serious adverse reactions associated with immunotherapy.
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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.
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Patients with past history of type I diabetes mellitus or HIV.
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Severe abnormalities in thyroid and cortisol testing; active, known or suspected autoimmune disease requiring systemic therapy.
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Patients with severe prior interstitial lung changes (as determined by the investigator).
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Patients with active tuberculosis and a strong positive OT test.
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Patients with active bleeding or severe coagulation dysfunction.
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Have had antitumor therapy, including endocrine, chemotherapy, radiotherapy, targeted therapy, immunotherapy and antitumor herbal therapy, 4 weeks prior to the first dose.
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Have not recovered to CTCAE 4.0 grade rating 0 or 1 level of toxicity after previous antineoplastic therapy.
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Current active hepatitis B, active hepatitis C, immunodeficiency virus or other active infection of clinical significance.
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Patients who have undergone surgery of grade 3 or higher or whose surgical wounds have not healed within 4 weeks prior to enrollment.
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Pregnant, lactating and planning to have children within six months.
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Subjects who, in the judgment of the investigator, are unsuitable for participation in this trial for any reason.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The PLA Navy Anqing Hospital | Anqing | Anhui | China | 246000 |
Sponsors and Collaborators
- Shanghai Yunying Medical Technology
- The PLA Navy Anqing Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AQNH-R130-AST