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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

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ClinicalTrials.gov Identifier: NCT01763645
Recruitment Status : Completed
First Posted : January 9, 2013
Results First Posted : October 24, 2016
Last Update Posted : March 30, 2018
Sponsor:
Information provided by (Responsible Party):
Biocad

Tracking Information
First Submitted Date  ICMJE December 27, 2012
First Posted Date  ICMJE January 9, 2013
Results First Submitted Date  ICMJE March 30, 2016
Results First Posted Date  ICMJE October 24, 2016
Last Update Posted Date March 30, 2018
Actual Study Start Date  ICMJE October 2012
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2016)
  • Overall Response Rate [ Time Frame: 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 [ 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) ]
    primary outcome measure for pharmacokinetics (PK) substudy
Original Primary Outcome Measures  ICMJE
 (submitted: January 7, 2013)
  • Overall Response Rate [ Time Frame: Day 127 ]
    primary outcome measure for efficacy evaluation
  • 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) ]
    primary outcome measure for pharmacokinetics (PK) substudy
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 31, 2016)
  • Complete Response Rate [ Time Frame: Day 127 ]
    secondary outcome measure for efficacy evaluation
  • Partial Response Rate [ Time Frame: Day 127 ]
    secondary outcome measure for efficacy evaluation
  • Stabilization Rate [ Time Frame: Day 127 ]
    secondary outcome measure for efficacy evaluation
  • Progression Rate [ Time Frame: Day 127 ]
    secondary outcome measure for efficacy evaluation
  • Occurrence of Anti-bevacizumab Antibodies [ Time Frame: Day 1 (before the drug administration), Day 15, 64 and 127 ]
    Secondary outcome measure for immunogenicity assessment
Original Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2013)
  • Complete Response Rate [ Time Frame: Day 127 ]
    secondary outcome measure for efficacy evaluation
  • Partial Response Rate [ Time Frame: Day 127 ]
    secondary outcome measure for efficacy evaluation
  • Stabilization Rate [ Time Frame: Day 127 ]
    secondary outcome measure for efficacy evaluation
  • Progression Rate [ Time Frame: Day 127 ]
    secondary outcome measure for efficacy evaluation
  • Relative number (%) of chemotherapy cycles, postponed due to adverse events (AE) [ Time Frame: Day 127 ]
    secondary outcome measure for safety evaluation
  • Treatment discontinuation rate due to AE [ Time Frame: Day 127 ]
    secondary outcome measure for safety evaluation
  • Occurrence and titer of anti-bevacizumab antibodies [ Time Frame: Day 1 (before the drug administration), Day 15, 64 and 127 ]
    Secondary outcome measure for immunogenicity assessment
  • Cmax [ Time Frame: Up to Day 22 ]
    secondary outcome measure for PK substudy
  • Tmax [ Time Frame: Up to Day 22 ]
    secondary outcome measure for PK substudy
  • T1/2 [ Time Frame: Up to Day 22 ]
    secondary outcome measure for PK substudy
  • AE incidence and severity [ Time Frame: Up to Day 148 ]
    secondary outcome measure for safety evaluation
  • AEs grade 3-4 incidence [ Time Frame: Up to Day 148 ]
    secondary outcome measure for safety evaluation
  • minimal serum bevacizumab concentration [ Time Frame: Day 22, Day 43, Day 64, Day 85, Day 106, Day 127 ]
    Secondary outcome measure for pharmacokinetics analysis
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Bevacizumab
    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).
    Other Names:
    • Avastin
    • BCD-021
  • Drug: Paclitaxel
    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)
    Other Name: Taxacad
  • Drug: 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).
Study Arms  ICMJE
  • Experimental: BCD-021 (CISC BIOCAD)
    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.
    Interventions:
    • Drug: Bevacizumab
    • Drug: Paclitaxel
    • Drug: Carboplatin
  • Active Comparator: Avastin (F. Hoffmann-La Roche Ltd)
    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.
    Interventions:
    • Drug: Bevacizumab
    • Drug: Paclitaxel
    • Drug: Carboplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 31, 2016)
138
Original Estimated Enrollment  ICMJE
 (submitted: January 7, 2013)
110
Actual Study Completion Date  ICMJE November 2014
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belarus,   India,   Russian Federation,   Ukraine
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01763645
Other Study ID Numbers  ICMJE BCD-021-02
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biocad
Study Sponsor  ICMJE Biocad
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Biocad
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP