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

Conditions: Non-small Cell Lung Cancer

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

Keywords: nsclc bevacizumab pharmacokinetics