Colorectal Cancer
Conditions
Keywords
Colorectal cancer, TLR5, Immunotherapy
Brief summary
Randomized Single-blind Placebo-controlled Clinical Study of Safety and Tolerability of CBLB502 as a Neo-adjuvant Treatment in Patients With Colorectal Cancer, With Different Doses and Regimens
Interventions
DRUGCBLB502
DRUGPlacebo
Sponsors
Cleveland BioLabs, Inc.
BioLab 612 LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written Patient Informed Consent for participation in the study 2. Men and women in the age above 18 years 3. Patients with confirmed diagnosis of colorectal cancer, indication to scheduled surgery for primary tumor removal 4. Should not have any previous anticancer therapy 5. Patient's life expectancy more than 3 months 6. ECOG performance status 0-1 7. Adequate hepatic and renal function: * Total bilirubin ≤1.5 upper limit of normal (ULN)), * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN, regardless of the presence of liver metastases, * Creatinine ≤2 x ULN 8. Adequate cardiac function including: * LVEF ≥45 by echocardiogram (ECHO) or multi gated acquisition scan, * 12-lead electrocardiogram (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention, * QTcB interval QT (QTc by Bazett's formula) \< 470 msec and no history of Torsades des Pointes or other symptomatic QTcB abnormality, * Absence of orthostatic hypotonia 9. Negative testing for serological markers of HIV-infection, viral hepatitis В and С, syphilis 10. Content to use barrier contraception methods by male/female patient and his/her partner in the study period
Exclusion criteria
1. Inability to obtain written Informеd consent for participation in the study 2. History of cardiovascular abnormalities including any conditions stated below: * Myocardial infarction/stroke for the last 6 months, * Stable abnormalities in regional contractility, * Cardiac failure (NYHA functional class III-IV), * Confirmed cardiomyopathy, * Clinically significant arrhythmias including any conditions stated below: * QT prolongation syndrome, * History of II or III-degree AV-block, * Bradycardia (HR \< 50 beats per min.) or tachycardia (HR \>100 beats per min.) * Blood pressure abnormalities: * 2 degree uncontrolled arterial hypertension (systolic blood pressure \> 160 mm Hg or diastolic blood pressure \> 105 mm Hg), * Hypotension (systolic blood pressure \< 90 mm Hg) 3. History of severe allergic, systemic and other oncologic diseases 4. Decompensated diabetes mellitus with glycolated hemoglobin level (HbA1c) \> 7% 5. Administration of drug products with evident effect on immune system for previous 3 months prior screening (including corticosteroids. Remark: Topical agents (e.g. for rash treatment), inhalation aerosols (e.g. for treatment of broncho-obstructive diseases), eye drops and agents for local administration (e.g. to joint cavity) is allowed 6. Participation in other clinical studies or administration of study products for 30 days prior screening, or persisting adverse reactions of the study product 7. Patients that have not taken CBLB502 8. Patients with hypersensitivity/allergy to CBLB502 or excipients of the drug product; NSAID (including ibuprofen) 9. Pregnant or lactating women 10. History of salmonellosis 11. Body mass \> 88 kg; no obesity which means BMI in the range 18.5-25 kg/m2 for women and 22-27 kg/m2 for men 12. Men and women of childbearing age which do agree to use double contraception method, oral contraception or abstain from sex contacts throughout the study 13. Alcohol abuse, drug abuse and any other medical, psychological and social reasons which may, in accordance with the investigator, affect patient's participation in the study, may prevent adequate assessment of the study results 14. Any conditions which are unstable or may endanger patient's safety and/or affect his/her adherence to the investigator instruction 15. Any patient is not able or willing to cooperate with the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability evaluation as measured by adverse events and assessed as changes in vital signs and clinical laboratory measurements, physical examination findings and ECG readings | Baseline to up to 14 days after the drug administration |
Secondary
| Measure | Time frame |
|---|---|
| Determination of levels of cytokine IL-6 in blood by multiplex assays | Baseline to up to 7 days after the drug administration |
| Determination of levels of cytokine IL-8 in blood by multiplex assays | Baseline to up to 7 days after the drug administration |
| Determination of levels of cytokine IL-10 in blood by multiplex assays | Baseline to up to 7 days after the drug administration |
| Determination of levels of cytokine G-CSF in blood by multiplex assays | Baseline to up to 7 days after the drug administration |
| Assessment of immune cells change in tumor by H&E and ICH staining | On Day 7 (Surgery day) after the drug administration |
| Specific T-cell responses measured by ELIspot | Baseline to up to 14 days after the drug administration |
| Antibody titer to CBLB502 as measured by ELISA | Baseline and on day 14 after the drug administration |
| Blood leukocytes by FACS | Baseline to up to 7 days after the drug administration |
| Determination of levels of cytokine TNFа in blood by multiplex assays | Baseline to up to 7 days after the drug administration |
Countries
Russia
Outcome results
None listed