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

• 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: Biocad
• Information provided by (Responsible Party): Biocad

Tracking Information

• First Submitted Date: December 27, 2012
• First Posted Date: January 9, 2013
• Results First Submitted Date: March 30, 2016
• Results First Posted Date: October 24, 2016
• Last Update Posted Date: March 30, 2018
• Actual Study Start Date: October 2012
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: 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: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 31, 2016): 138
• Original Estimated Enrollment (submitted: January 7, 2013): 110
• Actual Study Completion Date: November 2014
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belarus, India, Russian Federation, Ukraine

Administrative Information

• NCT Number: NCT01763645
• Other Study ID Numbers: BCD-021-02
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Biocad
• Study Sponsor: Biocad
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Biocad
• Verification Date: March 2018