A Safety and Efficacy Study of BCD-021 With Paclitaxel and Carboplatin Compared to Avastin With Paclitaxel and Carboplatin in Non-Small Cell Lung Cancer
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Bevacizumab; Paclitaxel; Carboplatin
Intervention description: Patients will receive 6 courses of bevacizumab in combination with carboplatin and paclitaxel. Bevacizumab will be administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each cycle).; Paclitaxel will be administered at a dose of 175 mg/m2 as 3 hour intravenous infusion on Day 1 of each 3-week course (6 courses totally); Carboplatin will be administered (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel on Day 1 of each 3-week course (6 courses totally).
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 353.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: NSCLC; bevacizumab; pharmacokinetics

Summary:

      BCD-021-02 is a double-blind randomized clinical trial comparing efficacy of BCD-021 (INN:
      bevacizumab) and paclitaxel + carboplatin to Avastin and paclitaxel + carboplatin in
      inoperable or advanced non-squamous NSCLC patients with pharmacokinetics substudy. The
      purpose of the study is to demonstrate the non-inferiority of efficacy and safety of BCD-021
      compared to Avastin. Also study includes pharmacokinetics assessment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent;

          -  Newly diagnosed histologically or cytologically confirmed NSCLC excluding squamous
             NSCLC (mixed cancer types should be classified according to the prevalent cell type);

          -  IIIb or IV stage of NSCLC (TNM classification version 6);

          -  Age ≥ 18 years and age ≤ 75 years (both inclusive);

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2, (not declining
             within 2 weeks prior to the first dose of investigational product);

          -  Life expectancy - 12 weeks or more from the moment of randomization;

          -  Presence of at least 1 measurable tumour with a size not less than 1 cm (revealed with
             CT slice thickness not more than 5 mm), as defined by modified Response Evaluation
             Criteria in Solid Tumors (RECIST) criteria (specifically, no ascites, pleural, or
             pericardial effusions, osteoblastic bone metastases, or carcinomatous lymphangitis of
             the lung as only lesion;

          -  Patients should be able to follow the Protocol procedures (according to Investigator's
             assessment);

          -  Patients must implement reliable contraceptive measures during all the study
             treatment, starting 4 weeks prior to the administration of the first dose of
             investigational product until 6 months after the last dose of investigational product.
             This requirement does not apply to participants who have undergone surgical
             sterilization, or patients who are postmenopausal (documented) for the past 2 years.
             Reliable contraceptive measures include two methods of contraception, including one
             barrier method

        Exclusion Criteria:

          -  Squamous NSCLC;

          -  Proven coagulopathy, clinically significant hemorrhage in the past including nasal
             hemorrhage;

          -  absolute neutrophil count <1500/mm3;

          -  Platelets <100 000/mm3;

          -  Hemoglobin < 90 g/L;

          -  Creatinine level ≥1.5 mg/dL;

          -  Bilirubin level ≥1.5 × upper limit of normal (ULN);

          -  Aspartate-aminotransferase(AST) and alanine-aminotransferase (ALT) levels ≥2.5 × ULN
             (≥5 × ULN for patients with liver metastases);

          -  Alkaline phosphatase level ≥5 × ULN;

          -  Current therapeutic anticoagulation treatment, aspirin (more than 325 mg/day),
             nonsteroidal anti-inflammatory drugs, antiplatelet agents or protracted treatment with
             these drugs less than 1 month before entering the study;

          -  Uncontrolled hypertension comprising all cases of arterial hypertension when no
             decrease in blood pressure could be achieved despite treatment with a combination of 3
             antihypertensive drugs including one diuretic and non-medical correction methods (low
             salt diet, physical exercise);

          -  Any previous anticancer therapy (chemotherapy, radiation therapy , surgery etc.) of
             metastatic NSCLC;

          -  Radiation or hormone therapy within 21 days prior to randomization;

          -  Major surgery 28 days before inclusion into the study;

          -  Previous antiangiogenic therapy;

          -  Hypersensitivity to taxanes, platinum agents, recombinant murine proteins, contrast
             agents, premedication agents specified by Protocol (dexamethasone, diphenhydramine,
             ranitidine) or excipients of investigational products;

          -  NSCLC metastases in central nervous system excluding metastases non-progressing
             without glucocorticosteroids within 4 weeks before inclusion into the trial;

          -  Cardiovascular system pathology (CHF stage III-IV according to New York Heart
             Association (NYHA) classification);

          -  Pregnancy or lactation;

          -  Conditions limiting patient's adherence to Protocol requirements (dementia, neurologic
             or psychiatric disorders, drug addiction, alcoholism and others);

          -  Stage II-IV neuropathy according to Common Terminology Criteria for Adverse Events
             (CTCAE) v.4.0;

          -  Simultaneous participation in other clinical trials, previous participation in other
             clinical trials within 30 days before entering into the trial, previous participation
             in the same trial;

          -  Any other concomitant cancer revealed within 5 years prior to screening, except
             curatively treated intraductal carcinoma in situ, curatively treated cervical
             carcinoma in situ or curatively treated basal cell or squamous cell carcinoma;

          -  Acute or active chronic infections;

          -  Hepatitis C virus, hepatitis B virus, HIV, or syphilis infections;

          -  Obstacles in intravenous administration of study drugs