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

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

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

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Placebo; Drug: CBLB502

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Federal State Budgetary Institution "State Scientific Center of Coloproctology named after A.N. Ryzhikh" Ministry of Health of the Russian Federation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 injection of CBLB502 0.35 μg/kg; One subcutaneous injection of CBLB502 0.35 μg/kg (not more 30 μg/injection) or Placebo at Day 1 before tumor removal	Drug: Placebo; Other Names: PBS; Phosphate buffer saline; Drug: CBLB502; Other Names: Entolimod
Experimental: 1 injection of CBLB502 0.45 μg/kg; One subcutaneous injection of CBLB502 0.45 μg/kg (not more 40 μg /injection) or Placebo at Day 1 before tumor removal	Drug: Placebo; Other Names: PBS; Phosphate buffer saline; Drug: CBLB502; Other Names: Entolimod
Experimental: 2 injections of CBLB502 0.35 μg/kg; 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: Placebo; Other Names: PBS; Phosphate buffer saline; Drug: CBLB502; Other Names: Entolimod
Experimental: 2 injections of CBLB502 0.45 μg/kg; 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: Placebo; Other Names: PBS; Phosphate buffer saline; Drug: CBLB502; Other Names: Entolimod

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: BioLab 612 LLC
• Collaborators: Cleveland BioLabs, Inc.
• Investigators: Principal Investigator: Sergei I. Achkasov, MD PhD, Federal State Budgetary Institution "State Scientific Center of Coloproctology named after A.N. Ryzhikh" Ministry of Health of the Russian Federation; Principal Investigator: Nikolay V. Kislov, MD PhD, Federal State Institution of Health of the Yaroslav Region "Regional Clinical Oncology Hospital"; Principal Investigator: Sergei V. Odintcov, MD PhD, Federal State Budgetary Institution "Central Clinical Hospital with polyclinic" Department of Presidential Affairs of the Russian Federation

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): February 1, 2017
• Study Completion (Anticipated): December 31, 2017

Study Registration Dates

• First Submitted: March 17, 2016
• First Submitted That Met QC Criteria: March 21, 2016
• First Posted (Estimate): March 22, 2016

Study Record Updates

• Last Update Posted (Estimate): February 9, 2017
• Last Update Submitted That Met QC Criteria: February 8, 2017
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Colorectal cancer; Immunotherapy; TLR5
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: BL612-CBLB502