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
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: CBLB502 (Drug)
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
干预措施: Placebo (Drug)
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
干预措施: CBLB502 (Drug)
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
干预措施: Placebo (Drug)
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
干预措施: CBLB502 (Drug)
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
干预措施: Placebo (Drug)
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
干预措施: CBLB502 (Drug)
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
干预措施: Placebo (Drug)
结局指标
主要结局
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
时间窗: Baseline to up to 14 days after the drug administration
次要结局
- 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)
- 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 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)