Clinical trial NCT02715882: Clinical Study of Safety and Tolerability of CBLB502 as a Neo-adjuvant Treatment in Patients With Colorectal Cancer
Official title: 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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: Colorectal cancer
TLR5
Immunotherapy
Lead sponsor: BioLab 612 LLC
Sponsor class: INDUSTRY
Collaborators: name: Cleveland BioLabs, Inc.
First posted: 2016-03-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline to up to 14 days after the drug administration
Secondary outcomes:
measure: Assessment of immune cells change in tumor by H&E and ICH staining
timeFrame: On Day 7 (Surgery day) after the drug administration
measure: Determination of levels of cytokine IL-6 in blood by multiplex assays
timeFrame: Baseline to up to 7 days after the drug administration
measure: Determination of levels of cytokine IL-8 in blood by multiplex assays
timeFrame: Baseline to up to 7 days after the drug administration
measure: Determination of levels of cytokine IL-10 in blood by multiplex assays
timeFrame: Baseline to up to 7 days after the drug administration
measure: Determination of levels of cytokine G-CSF in blood by multiplex assays
timeFrame: Baseline to up to 7 days after the drug administration
measure: Determination of levels of cytokine TNFа in blood by multiplex assays
timeFrame: Baseline to up to 7 days after the drug administration
measure: Specific T-cell responses measured by ELIspot
timeFrame: Baseline to up to 14 days after the drug administration
measure: Antibody titer to CBLB502 as measured by ELISA
timeFrame: Baseline and on day 14 after the drug administration
measure: Blood leukocytes by FACS
timeFrame: Baseline to up to 7 days after the drug administration
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution "State Scientific Center of Coloproctology named after A.N. Ryzhikh" Ministry of Health of the Russian Federation
Study officials:
affiliation: Federal State Budgetary Institution "State Scientific Center of Coloproctology named after A.N. Ryzhikh" Ministry of Health of the Russian Federation
name: Sergei I. Achkasov, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal State Institution of Health of the Yaroslav Region "Regional Clinical Oncology Hospital"
name: Nikolay V. Kislov, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal State Budgetary Institution "Central Clinical Hospital with polyclinic" Department of Presidential Affairs of the Russian Federation
name: Sergei V. Odintcov, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: