Assess the Safety and Tolerability of Various Doses and Dosing Schedules of EnteroMix in Patients With a Histologically Confirmed Solid Tumor
Conditions
Keywords
solid tumors, oncolytic viruses, vaccine
Brief summary
The study will include adult patients of either sex with a histologically confirmed solid tumor who are ineligible for surgery and for whom all available pharmacological and radiotherapeutic options have been exhausted. The choice of drug administration route will depend on the extent of the tumor process. In patients with metastatic disease confirmed by imaging methods (CT/MRI/PET-CT as indicated, with assessment according to RECIST 1.1 criteria for solid tumors and RANO criteria for neuro-oncological tumors), EnteroMix will be administered intravenously. In patients with massive locally advanced disease without distant metastases, or with generalized disease showing an isolated progressive lesion confirmed by imaging methods (CT/MRI/PET-CT as indicated, with assessment according to RECIST 1.1 criteria for solid tumors and RANO criteria for neuro-oncological tumors), EnteroMix will be administered intra-arterially (into the afferent artery of the tumor).
Interventions
BIOLOGICALTwo cohorts of patients: intravenous administration and intra-arterial administration with dose escalation of the drug.
\- Single administration of the investigational drug with dose escalation to determine the optimal dose with respect to safety, pharmacokinetics, and therapeutic effect. EnteroMix will be administered once at three dose levels: * 0.5×10⁶ PFU/kg (Cohort 1.1 - intravenous, Cohort 1.4 - intra-arterial); * 5×10⁶ PFU/kg (Cohort 1.2 - intravenous, Cohort 1.5 - intra-arterial); * 5×10⁷ PFU/kg (Cohort 1.3 - intravenous, Cohort 1.6 - intra-arterial). * Double administration of the investigational drug at the optimal dose selected based on the results of the first stage. EnteroMix will be administered twice with a 10-day interval (Cohort 2.1 - intravenous, Cohort 2.2 - intra-arterial). \- Triple administration of the investigational drug at the optimal dose selected based on the results of the first stage. EnteroMix will be administered three times with a 10-day interval (Cohort 3.1 - intravenous, Cohort 3.2 - intra-arterial). The standard 3+3 design for phase I oncology trials is used.
Sponsors
National Medical Research Radiological Centre of the Ministry of Health of Russia
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Men and women aged 18-75 years inclusive; * Histologically confirmed diagnosis of a solid tumor; * Patients in whom surgical intervention is contraindicated; * Patients with exhausted methods of drug and radiation therapy; * General health status on the ECOG 0-2 scale; * Life expectancy of at least 3 months; * Acceptable indicators of a general blood test: hemoglobin ≥ 90 g/l; absolute number of neutrophils ≥ 1500/mm3; platelet count ≥ 100,000/mm3; * Glomerular filtration rate calculated according to the formula CKD-EPI\* ≥ 60 ml/min/1.73 m2; * Quick's prothrombin is more than 55%; * Acceptable indicators of liver function according to biochemical blood analysis: serum bilirubin \< 1.5 x ULN; AST \< 2.5 x ULN (or \< 5 x ULN in patients with liver metastases); ALT \< 2.5 x ULN (or \< 5 x ULN in patients with liver metastases); * Since the previous antitumor therapy (chemotherapy, targeted therapy, radiotherapy, immunotherapy) at least 30 days or at least 5 half-lives should elapse before the administration of the investigational drug; * Patients should recover from any previous surgery, radiotherapy, localized therapy, or systemic therapy to the 1st or lower degree of severity of adverse reactions (with the exception of alopecia or anemia, for which the 2nd degree of severity is allowed); * Women with preserved reproductive potential (who are not menopausal and have not undergone surgical sterilization) and men who are sexually active should use a reliable method of contraception (acceptable methods of contraception in this study are: intrauterine devices, oral contraceptives, contraceptive patch, long-acting injectable contraceptives, double barrier method (condom and spermicide, diaphragm and spermicide) during the study and at least 62 days after taking the last dose of the drug; * The ability to follow the procedures specified in the protocol during the entire study period; The patient's informed consent to participate in the clinical trial.
Exclusion criteria
* Withdrawal of consent to participate in the study.The development of severe or intolerable AES, which, in the researcher's opinion, make the patient's further participation in the study impossible. * Detection of HIV infection during the study; * According to the researcher, further participation in the study is not in the best interests of the patient. * There is a poor response to the study therapy, expressed by the progression of the disease in accordance with the criteria of RECIST 1.1 (RANO for neuroendocrine tumors) or worsening of clinical symptoms and / or laboratory * According to the researcher, the patient is not committed to the protocol requirements. * Deviations from the protocol, which, in the opinion of the sponsor or researcher, require the exclusion of the patient from the study.The onset of pregnancy; * The patient was included in the study with a violation of compliance with the inclusion/non-inclusion criteria. * Loss of contact with the patient for follow-up. * Death of the patient. * The decision of the sponsor or researcher for a reason not specified above.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Quantitative content of the viral drug in the peripheral blood of patients: | Day -1, Day 0, Day 1, Day 2, Day 3 |
Countries
Russia
Outcome results
None listed