A Safety and Efficacy Study of BCD-021 With Paclitaxel an... | NCT01763645

NCT01763645

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BCD-021 (CISC BIOCAD)	Experimental	BCD-021 is a product code for bevacizumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 will be administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel will be administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.	Drug: Bevacizumab Drug: Paclitaxel Drug: Carboplatin
Avastin (F. Hoffmann-La Roche Ltd)	Active Comparator	In this arm patients will receive 6 courses of treatment with Avastin in combination with carboplatin and paclitaxel. Avastin will be administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks on Day 1. Paclitaxel will be administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.	Drug: Bevacizumab Drug: Paclitaxel Drug: Carboplatin

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Bevacizumab	Drug	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).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Response Rate	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Day 127
Area Under the Curve After the First Test Drug Administration	primary outcome measure for pharmacokinetics (PK) substudy	up to Day 22, after the first bevacizumab administration (time points for blood samples: 0 h 1.5 h, 3 h, 4.5 h, 6 h, 24 h, 96 h, 168 h, 336 h and 504 h)

Measure	Description	Time Frame
Complete Response Rate	secondary outcome measure for efficacy evaluation	Day 127
Partial Response Rate	secondary outcome measure for efficacy evaluation

Eligibility Module

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

Contacts/Locations Module

Name	Affiliation	Role
Yulia Linkova, MD, PhD	Director of Clinical Development Department, BIOCAD	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Brest Regional Clinical Dispensary		Brest			Belarus
Grodno Regional Clinical Hospital

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35105329	Derived	Stroyakovskiy DL, Fadeeva NV, Matrosova MP, Shelepen KG, Adamchuk GA, Roy B, Nagarkar R, Kalloli M, Zhuravleva D, Voevodin GD, Shustova MS, Kryukov F. Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-021 with reference bevacizumab. BMC Cancer. 2022 Feb 1;22(1):129. doi: 10.1186/s12885-022-09243-7.

Label	URL
Stroyakovskiy, D.L., Fadeeva, N.V., Matrosova, M.P. et al. Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-021 with reference bevacizumab. BMC Cancer 22, 129 (2022). https://doi.org/10.1186/s12885-022-09243-7	View source

ID	Title	Description
FG000	BCD-021 (CISC BIOCAD)	In this arm patients received 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.

Categories

Title	Measurements
	OG00034.63 OG00133.82

Primary

Area Under the Curve After the First Test Drug Administration

primary outcome measure for pharmacokinetics (PK) substudy

Patients who received one dose of study drug and after 504 hours after injection had missed <= 1 blood sample collection to analyze pharmacokinetics.

Posted

Median

Full Range

(ng/ml)*hour

up to Day 22, after the first bevacizumab administration (time points for blood samples: 0 h 1.5 h, 3 h, 4.5 h, 6 h, 24 h, 96 h, 168 h, 336 h and 504 h)

ID	Title	Description
OG000	BCD-021 (CISC BIOCAD)	In this arm patients received 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.
OG001	Avastin (F. Hoffmann-La Roche Ltd)	In this arm patients received 6 courses of treatment with Avastin in combination with carboplatin and paclitaxel. Avastin was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks on Day 1. Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.

Secondary

Complete Response Rate

secondary outcome measure for efficacy evaluation

Posted

Number

95% Confidence Interval

percentage of patients

Day 127

ID	Title	Description
OG000	BCD-021 (CISC BIOCAD)	In this arm patients received 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.
OG001	Avastin (F. Hoffmann-La Roche Ltd)	In this arm patients received 6 courses of treatment with Avastin in combination with carboplatin and paclitaxel. Avastin was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks on Day 1. Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.

Units	Counts
Participants

Secondary

Partial Response Rate

secondary outcome measure for efficacy evaluation

Posted

Number

95% Confidence Interval

percentage of patients

Day 127

ID	Title	Description
OG000	BCD-021 (CISC BIOCAD)	In this arm patients received 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.
OG001	Avastin (F. Hoffmann-La Roche Ltd)	In this arm patients received 6 courses of treatment with Avastin in combination with carboplatin and paclitaxel. Avastin was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks on Day 1. Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.

Units	Counts
Participants

Secondary

Stabilization Rate

secondary outcome measure for efficacy evaluation

Posted

Number

95% Confidence Interval

percentage of patients

Day 127

ID	Title	Description
OG000	BCD-021 (CISC BIOCAD)	In this arm patients received 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.
OG001	Avastin (F. Hoffmann-La Roche Ltd)	In this arm patients received 6 courses of treatment with Avastin in combination with carboplatin and paclitaxel. Avastin was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks on Day 1. Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.

Units	Counts
Participants

Secondary

Progression Rate

secondary outcome measure for efficacy evaluation

Posted

Number

95% Confidence Interval

percentage of patients

Day 127

ID	Title	Description
OG000	BCD-021 (CISC BIOCAD)	In this arm patients received 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.
OG001	Avastin (F. Hoffmann-La Roche Ltd)	In this arm patients received 6 courses of treatment with Avastin in combination with carboplatin and paclitaxel. Avastin was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks on Day 1. Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.

Units	Counts
Participants

Secondary

Occurrence of Anti-bevacizumab Antibodies

Secondary outcome measure for immunogenicity assessment

Posted

Number

percentage of patients

Day 1 (before the drug administration), Day 15, 64 and 127

ID	Title	Description
OG000	BCD-021 (CISC BIOCAD)	In this arm patients received 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.
OG001	Avastin (F. Hoffmann-La Roche Ltd)	In this arm patients received 6 courses of treatment with Avastin in combination with carboplatin and paclitaxel. Avastin was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks on Day 1. Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.

Units	Counts

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	BCD-021 (CISC BIOCAD)	In this arm patients received 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1. Data on adverse events was collected from date of signing informed consent up to 18 weeks after first injection of study drug.	14	206	36	206	206	206
EG001	Avastin (F. Hoffmann-La Roche Ltd)	In this arm patients received 6 courses of treatment with Avastin in combination with carboplatin and paclitaxel. Avastin was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks on Day 1. Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1. Data on adverse events was collected from date of signing informed consent up to 18 weeks after first injection of study drug.	8	137	20	137	137	137

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0005 events5 affected206 at risk EG0013 events3 affected137 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected137 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected137 at risk
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 events1 affected206 at risk EG0011 events1 affected137 at risk
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0002 events2 affected206 at risk EG0011 events1 affected137 at risk
Leukopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected206 at risk EG0011 events1 affected137 at risk
Pancytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk
Deafness neurosensory	Ear and labyrinth disorders	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected137 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0002 events1 affected206 at risk EG0010 events0 affected137 at risk
Fournier's gangrene	Infections and infestations	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected137 at risk
Respiratory tract infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk
Neutropenic sepsis	Infections and infestations	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected137 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected137 at risk
Gastroenteritis	Infections and infestations	Systematic Assessment	EG0003 events3 affected206 at risk EG0010 events0 affected137 at risk
Scrotal infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk
Transient ischaemic attack	Nervous system disorders	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk
Death	General disorders	Systematic Assessment	EG0003 events3 affected206 at risk EG0012 events2 affected137 at risk
Disease progression	General disorders	Systematic Assessment	EG0003 events3 affected206 at risk EG0011 events1 affected137 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk
Proctitis	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected206 at risk EG0011 events1 affected137 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected137 at risk
Enteritis	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk
Gastrointestinal inflammation	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk
Poisoning	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk
Cardio-respiratory arrest	Cardiac disorders	Systematic Assessment	EG0001 events1 affected206 at risk EG0011 events1 affected137 at risk
Hypertension	Vascular disorders	Systematic Assessment	EG0001 events1 affected206 at risk EG0011 events1 affected137 at risk
Hypovolaemic shock	Vascular disorders	Systematic Assessment	EG0000 events0 affected206 at risk EG0011 events1 affected137 at risk
Hyponatraemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected206 at risk EG0010 events0 affected137 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	Systematic Assessment	EG000104 events104 affected206 at risk EG00178 events78 affected137 at risk
Thrombocytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG00060 events60 affected206 at risk EG00142 events42 affected137 at risk
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG00045 events45 affected206 at risk EG00137 events37 affected137 at risk
Leukopenia	Blood and lymphatic system disorders	Systematic Assessment	EG00042 events42 affected206 at risk EG00139 events39 affected137 at risk
Leukocytosis	Blood and lymphatic system disorders	Systematic Assessment	EG00025 events25 affected206 at risk EG00125 events25 affected137 at risk
Neutrophilia	Blood and lymphatic system disorders	Systematic Assessment	EG00019 events19 affected206 at risk EG00127 events27 affected137 at risk
Lymphopenia	Blood and lymphatic system disorders	Systematic Assessment	EG00023 events23 affected206 at risk EG00118 events18 affected137 at risk
Erythropenia	Blood and lymphatic system disorders	Systematic Assessment	EG00017 events17 affected206 at risk EG00115 events15 affected137 at risk
Thrombocytosis	Blood and lymphatic system disorders	Systematic Assessment	EG00014 events14 affected206 at risk EG00117 events17 affected137 at risk
Lymphocytosis	Blood and lymphatic system disorders	Systematic Assessment	EG00013 events13 affected206 at risk EG00116 events16 affected137 at risk
Polycythaemia	Blood and lymphatic system disorders	Systematic Assessment	EG00010 events10 affected206 at risk EG0013 events3 affected137 at risk
Blood lactate dehydrogenase increased	Investigations	Systematic Assessment	EG00025 events25 affected206 at risk EG00120 events20 affected137 at risk
Blood alkaline phosphatase increased	Investigations	Systematic Assessment	EG00022 events22 affected206 at risk EG00118 events18 affected137 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG00019 events19 affected206 at risk EG00117 events17 affected137 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG00017 events17 affected206 at risk EG00114 events14 affected137 at risk
Blood uric acid increased	Investigations	Systematic Assessment	EG00018 events18 affected206 at risk EG00112 events12 affected137 at risk
White blood cell count decreased	Investigations	Systematic Assessment	EG00020 events20 affected206 at risk EG0019 events9 affected137 at risk
Blood creatinine increased	Investigations	Systematic Assessment	EG00012 events12 affected206 at risk EG00111 events11 affected137 at risk
Blood pressure systolic increased	Investigations	Systematic Assessment	EG00012 events12 affected206 at risk EG0015 events5 affected137 at risk
Blood urea increased	Investigations	Systematic Assessment	EG0006 events6 affected206 at risk EG00111 events11 affected137 at risk
Asthenia	General disorders	Systematic Assessment	EG00026 events26 affected206 at risk EG00117 events17 affected137 at risk
Pyrexia	General disorders	Systematic Assessment	EG00023 events23 affected206 at risk EG00114 events14 affected137 at risk
Pain	General disorders	Systematic Assessment	EG00016 events16 affected206 at risk EG0016 events6 affected137 at risk
Alopecia	Skin and subcutaneous tissue disorders	Systematic Assessment	EG00053 events53 affected206 at risk EG00127 events27 affected137 at risk
Hyperglycaemia	Metabolism and nutrition disorders	Systematic Assessment	EG00039 events39 affected206 at risk EG00134 events34 affected137 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG00022 events22 affected206 at risk EG00110 events10 affected137 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG00013 events13 affected206 at risk EG0019 events9 affected137 at risk
Neuropathy peripheral	Nervous system disorders	Systematic Assessment	EG00023 events23 affected206 at risk EG00116 events16 affected137 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00011 events11 affected206 at risk EG0017 events7 affected137 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0006 events6 affected206 at risk EG0018 events8 affected137 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0005 events5 affected206 at risk EG0017 events7 affected137 at risk
Hypertension	Vascular disorders	Systematic Assessment	EG00020 events20 affected206 at risk EG0019 events9 affected137 at risk
Tachycardia	Cardiac disorders	Systematic Assessment	EG00014 events14 affected206 at risk EG0017 events7 affected137 at risk

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung

Ancestor Terms

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D000068258	Bevacizumab
D017239	Paclitaxel
D016190	Carboplatin

Ancestor Terms

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D056831	Coordination Complexes

ID	Title	Description
BG000	BCD-021 (CISC BIOCAD)	In this arm patients received 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.
BG001	Avastin (F. Hoffmann-La Roche Ltd)	In this arm patients received 6 courses of treatment with Avastin in combination with carboplatin and paclitaxel. Avastin was administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks on Day 1. Paclitaxel was administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.
BG002	Total	Total of all reporting groups