Overview

This trial is active, not recruiting.

Condition non-small cell lung cancer
Treatments bevacizumab, paclitaxel, carboplatin
Phase phase 3
Target VEGF
Sponsor Biocad
Start date October 2012
End date November 2015
Trial size 214 participants
Trial identifier NCT01763645, BCD-021-02

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(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.
bevacizumab Avastin
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 Taxacad
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
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).
(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.
bevacizumab Avastin
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 Taxacad
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
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).

Primary Outcomes

Measure
Overall response rate
time frame: Day 127
Area under the curve after the first test drug administration
time frame: 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)

Secondary Outcomes

Measure
Complete response rate
time frame: Day 127
Partial response rate
time frame: Day 127
Stabilization rate
time frame: Day 127
Progression rate
time frame: Day 127
Relative number (%) of chemotherapy cycles, postponed due to adverse events (AE)
time frame: Day 127
Treatment discontinuation rate due to AE
time frame: Day 127
Occurrence and titer of anti-bevacizumab antibodies
time frame: Day 1 (before the drug administration), Day 15, 64 and 127
Cmax
time frame: Up to Day 22
Tmax
time frame: Up to Day 22
T1/2
time frame: Up to Day 22
AE incidence and severity
time frame: Up to Day 148
AEs grade 3-4 incidence
time frame: Up to Day 148
minimal serum bevacizumab concentration
time frame: Day 22, Day 43, Day 64, Day 85, Day 106, Day 127

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

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 metastatc 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

Additional Information

Official title International Multicenter Randomized Double Blind Phase III Trial Comparing Safety and Efficacy of BCD-021 (CJSC BIOCAD, Russia) and Paclitaxel + Carboplatin to Avastin® (F. Hoffmann-La Roche Ltd, Switzerland) and Paclitaxel + Carboplatin in Inoperable or Advanced Non-squamous Non-small-cell Lung Cancer (NSCLC) Patients
Trial information was received from ClinicalTrials.gov and was last updated in February 2015.
Information provided to ClinicalTrials.gov by Biocad.