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
Phase 3
Completed
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT01763645
- Lead Sponsor
- Biocad
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 353
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BCD-021 (CISC BIOCAD) Paclitaxel 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. BCD-021 (CISC BIOCAD) Bevacizumab 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. BCD-021 (CISC BIOCAD) Carboplatin 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. Avastin (F. Hoffmann-La Roche Ltd) Bevacizumab 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. Avastin (F. Hoffmann-La Roche Ltd) Paclitaxel 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. Avastin (F. Hoffmann-La Roche Ltd) Carboplatin 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.
- Primary Outcome Measures
Name Time Method Overall Response Rate Day 127 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.
Area Under the Curve After the First Test Drug Administration 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) primary outcome measure for pharmacokinetics (PK) substudy
- Secondary Outcome Measures
Name Time Method Occurrence of Anti-bevacizumab Antibodies Day 1 (before the drug administration), Day 15, 64 and 127 Secondary outcome measure for immunogenicity assessment
Partial Response Rate Day 127 secondary outcome measure for efficacy evaluation
Stabilization Rate Day 127 secondary outcome measure for efficacy evaluation
Complete Response Rate Day 127 secondary outcome measure for efficacy evaluation
Progression Rate Day 127 secondary outcome measure for efficacy evaluation
Trial Locations
- Locations (44)
Brest Regional Clinical Dispensary
🇧🇾Brest, Belarus
Gomel Regional Clinical Oncology Dispensary
🇧🇾Gomel, Belarus
Grodno Regional Clinical Hospital
🇧🇾Grodno, Belarus
Vitebsk Regional Clinical Oncology Dispensary
🇧🇾Vitebsk, Belarus
HCG Bangalore Institute of Oncology
🇮🇳Bangalore, India
M.S.Ramaiah Memorial Hospital
🇮🇳Bangalore, India
Narayana Hrudayalaya Hospitals
🇮🇳Bangalore, India
Arkhangelsk District Clinical Oncology Dispensary
🇷🇺Arkhangelsk, Russian Federation
Non-governmental Healthcare Institution "Railway Clinical hospital on the Chelyabinsk Station of JSC Russian Railways"
🇷🇺Chelyabinsk, Russian Federation
State-financed Health Institution "Chelyabinsk Region Clinical Oncology Dispansary"
🇷🇺Chelyabinsk, Russian Federation
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