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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Non-small Cell Lung Cancer
Interventions Drug: Bevacizumab
Drug: Paclitaxel
Drug: Carboplatin
Enrollment 138
Recruitment Details  
Pre-assignment Details 134 of 138 patients received at least one dose of the study drug/comparator. 4 patients discontinued the study without receiving a single dose of the study drug/comparator. 88 patients received all 6 therapy cycles and completed the main study period in accordance with the Protocol. 50 subjects withdrew from the study.
Arm/Group Title BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd)
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 69 69
Received at Least 1 Dose of Study Drug 68 66
Completed 43 [1] 45 [1]
Not Completed 26 24
[1]
Completed the study according the protocol.
Arm/Group Title BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd) Total
Hide Arm/Group Description 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.

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.

 Total of all reporting groups
Overall Number of Baseline Participants 68 66 134
Hide Baseline Analysis Population Description
Patients who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 68 participants 66 participants 134 participants
57.79  (8.88) 58.67  (8.33) 58.23  (8.61)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 66 participants 134 participants
Female
25
  36.8%
24
  36.4%
49
  36.6%
Male
43
  63.2%
42
  63.6%
85
  63.4%
1.Primary Outcome
Title Overall Response Rate
Hide Description 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.
Time Frame Day 127
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis included only those patients who received at least one dose of BCD-021 or Avastin®, and in whom it was possible to assess the response to therapy.
Arm/Group Title BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd)
Hide Arm/Group Description:
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.

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.
Overall Number of Participants Analyzed 54 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participans
42.59
(30.33 to 55.83)
39.29
(27.58 to 52.27)
2.Primary Outcome
Title Area Under the Curve After the First Test Drug Administration
Hide Description primary outcome measure for pharmacokinetics (PK) substudy
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)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who received one dose of study drug and after 504 hours after injection had missed <= 1 blood sample collection to analyze pharmacokinetics.
Arm/Group Title BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 67 64
Median (Inter-Quartile Range)
Unit of Measure: (ng/ml)*hour
66869
(36702 to 77907)
58844
(42197 to 84329)
3.Secondary Outcome
Title Complete Response Rate
Hide Description secondary outcome measure for efficacy evaluation
Time Frame Day 127
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 54 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
1.85
(0.33 to 9.77)
1.79
(0.32 to 9.45)
4.Secondary Outcome
Title Partial Response Rate
Hide Description secondary outcome measure for efficacy evaluation
Time Frame Day 127
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 54 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
40.74
(28.68 to 54.03)
37.50
(26.01 to 50.59)
5.Secondary Outcome
Title Stabilization Rate
Hide Description secondary outcome measure for efficacy evaluation
Time Frame Day 127
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 54 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
51.85
(38.85 to 64.60)
51.79
(39.01 to 64.34)
6.Secondary Outcome
Title Progression Rate
Hide Description secondary outcome measure for efficacy evaluation
Time Frame Day 127
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 54 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
5.56
(1.91 to 15.11)
8.93
(3.88 to 19.26)
7.Secondary Outcome
Title Occurrence of Anti-bevacizumab Antibodies
Hide Description Secondary outcome measure for immunogenicity assessment
Time Frame Day 1 (before the drug administration), Day 15, 64 and 127
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 68 66
Measure Type: Number
Unit of Measure: percentage of patients
1.47 1.52
Time Frame 6 therapy cycles
Adverse Event Reporting Description The safety analysis included all subjects who received at least one dose of BCD-021 or Avastin® (n = 134).
 
Arm/Group Title BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd)
Hide Arm/Group Description

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.

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.
All-Cause Mortality
BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/68 (20.59%)      8/66 (12.12%)    
Blood and lymphatic system disorders     
Neutropenia †  1/68 (1.47%)  1 0/66 (0.00%)  0
Leucopenia †  1/68 (1.47%)  1 0/66 (0.00%)  0
Cardiac disorders     
Transient ischemic attack †  1/68 (1.47%)  1 0/66 (0.00%)  0
Ear and labyrinth disorders     
Sensorineural hearing loss †  0/68 (0.00%)  0 1/66 (1.52%)  1
Gastrointestinal disorders     
Paraproctitis †  1/68 (1.47%)  2 1/66 (1.52%)  1
General disorders     
Endogenous intoxication †  1/68 (1.47%)  1 0/66 (0.00%)  0
Death for an unknown reason †  1/68 (1.47%)  1 1/66 (1.52%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Disease progression †  2/68 (2.94%)  2 1/66 (1.52%)  1
Respiratory, thoracic and mediastinal disorders     
Pneumonia †  2/68 (2.94%)  2 0/66 (0.00%)  0
Pulmonary hemorrhage †  4/68 (5.88%)  4 2/66 (3.03%)  2
Hemoptysis with febrile fever †  1/68 (1.47%)  1 0/66 (0.00%)  0
Spontaneous pneumothorax with hydrothorax †  0/68 (0.00%)  0 1/66 (1.52%)  1
Dyspnea †  0/68 (0.00%)  0 1/66 (1.52%)  1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BCD-021 (CISC BIOCAD) Avastin (F. Hoffmann-La Roche Ltd)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   68/68 (100.00%)      66/66 (100.00%)    
Blood and lymphatic system disorders     
Leucopenia †  54/68 (79.41%)  50/66 (75.76%) 
Leucocytosis †  33/68 (48.53%)  32/66 (48.48%) 
Neutropenia †  58/68 (85.29%)  52/66 (78.79%) 
Anemia †  60/68 (88.24%)  56/66 (84.85%) 
Trombocytopenia †  47/68 (69.12%)  41/66 (62.12%) 
Elevated absolute neutrophil count †  28/68 (41.18%)  33/66 (50.00%) 
Elevated hemoglobin †  5/68 (7.35%)  3/66 (4.55%) 
Lymphopenia †  33/68 (48.53%)  31/66 (46.97%) 
Lymphocytosis †  14/68 (20.59%)  18/66 (27.27%) 
Erythropenia †  23/68 (33.82%)  18/66 (27.27%) 
Erythrocytosis †  10/68 (14.71%)  5/66 (7.58%) 
Trombocytosis †  19/68 (27.94%)  28/66 (42.42%) 
Cardiac disorders     
Tachycardia †  20/68 (29.41%)  10/66 (15.15%) 
Gastrointestinal disorders     
nausea †  9/68 (13.24%)  9/66 (13.64%) 
diarrhea †  6/68 (8.82%)  3/66 (4.55%) 
General disorders     
Fever †  4/68 (5.88%)  4/66 (6.06%) 
Generalized weakness †  12/68 (17.65%)  11/66 (16.67%) 
Hepatobiliary disorders     
Elevated alkaline phosphotase †  24/68 (35.29%)  20/66 (30.30%) 
Elevated AST †  21/68 (30.88%)  15/66 (22.73%) 
Elevated ALT †  18/68 (26.47%)  19/66 (28.79%) 
Hyperbilirubinemia †  1/68 (1.47%)  4/66 (6.06%) 
Elevated direct bilirubin †  4/68 (5.88%)  2/66 (3.03%) 
Infections and infestations     
Acute respiratory viral infection †  0/68 (0.00%)  4/66 (6.06%) 
Investigations     
Elevated lactate dehydrohenase †  33/68 (48.53%)  25/66 (37.88%) 
Metabolism and nutrition disorders     
Hyperglycemia †  42/68 (61.76%)  37/66 (56.06%) 
Hyperuricemia †  22/68 (32.35%)  14/66 (21.21%) 
Musculoskeletal and connective tissue disorders     
Arthralgia †  7/68 (10.29%)  9/66 (13.64%) 
Myalgia †  5/68 (7.35%)  5/66 (7.58%) 
Ossalgia †  5/68 (7.35%)  4/66 (6.06%) 
Nervous system disorders     
Peripheral neuropathy †  8/68 (11.76%)  8/66 (12.12%) 
Renal and urinary disorders     
Elevated urea †  11/68 (16.18%)  12/66 (18.18%) 
Elevated creatinine †  16/68 (23.53%)  12/66 (18.18%) 
Respiratory, thoracic and mediastinal disorders     
Lung hemorrhage †  4/68 (5.88%)  2/66 (3.03%) 
Dyspnea †  5/68 (7.35%)  6/66 (9.09%) 
Skin and subcutaneous tissue disorders     
Alopecia †  21/68 (30.88%)  16/66 (24.24%) 
Vascular disorders     
Arterial hypertension †  18/68 (26.47%)  15/66 (22.73%) 
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Biryulin Andrey
Organization: BIOCAD
Phone: +7812380 49 33 ext 925
EMail: biryulin@biocad.ru
Layout table for additonal information
Responsible Party: Biocad
ClinicalTrials.gov Identifier: NCT01763645    
Other Study ID Numbers: BCD-021-02
First Submitted: December 27, 2012
First Posted: January 9, 2013
Results First Submitted: March 30, 2016
Results First Posted: October 24, 2016
Last Update Posted: March 30, 2018