Clinical Study of Safety and Tolerability of CBLB502 as a Neo-adjuvant Treatment in Patients With Colorectal Cancer

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: CBLB502
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written Patient Informed Consent for participation in the study Men and women in the age above 18 years Patients with confirmed diagnosis of colorectal cancer, indication to scheduled surgery for primary tumor removal Should not have any previous anticancer therapy Patient's life expectancy more than 3 months ECOG performance status 0-1 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 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 Negative testing for serological markers of HIV-infection, viral hepatitis В and С, syphilis Content to use barrier contraception methods by male/female patient and his/her partner in the study period Exclusion Criteria: Inability to obtain written Informеd consent for participation in the study 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) History of severe allergic, systemic and other oncologic diseases Decompensated diabetes mellitus with glycolated hemoglobin level (HbA1c) > 7% 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 Participation in other clinical studies or administration of study products for 30 days prior screening, or persisting adverse reactions of the study product Patients that have not taken CBLB502 Patients with hypersensitivity/allergy to CBLB502 or excipients of the drug product; NSAID (including ibuprofen) Pregnant or lactating women History of salmonellosis 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 Men and women of childbearing age which do agree to use double contraception method, oral contraception or abstain from sex contacts throughout the study 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 Any conditions which are unstable or may endanger patient's safety and/or affect his/her adherence to the investigator instruction Any patient is not able or willing to cooperate with the investigator

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 injection of CBLB502 0.35 μg/kg<br>One subcutaneous injection of CBLB502 0.35 μg/kg (not more 30 μg/injection) or Placebo at Day 1 before tumor removal | Drug: CBLB502<br> <br> * Other names: Entolimod;Drug: Placebo<br> <br> * Other names: Phosphate buffer saline;|
| Experimental: 1 injection of CBLB502 0.45 μg/kg<br>One subcutaneous injection of CBLB502 0.45 μg/kg (not more 40 μg /injection) or Placebo at Day 1 before tumor removal | Drug: CBLB502<br> <br> * Other names: Entolimod;Drug: Placebo<br> <br> * Other names: Phosphate buffer saline;|
| Experimental: 2 injections of CBLB502 0.35 μg/kg<br>Two subcutaneous injections of CBLB502 0.35 μg/kg (not more 30 μg/injection) or Placebo at Day 1 and Day 4 before tumor removal | Drug: CBLB502<br> <br> * Other names: Entolimod;Drug: Placebo<br> <br> * Other names: Phosphate buffer saline;|
| Experimental: 2 injections of CBLB502 0.45 μg/kg<br>Two subcutaneous injections of CBLB502 at 0.45 μg/kg (not more 40 μg /injection) or Placebo at Day 1 and Day 4 before tumor removal | Drug: CBLB502<br> <br> * Other names: Entolimod;Drug: Placebo<br> <br> * Other names: Phosphate buffer saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of immune cells change in tumor by H&E and ICH staining |  | On Day 7 (Surgery day) after the drug administration | 
| 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 | 
| Determination of levels of cytokine TNFа in blood by multiplex assays |  | Baseline to up to 7 days 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, TLR5, Immunotherapy