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Trial record 31 of 66 for:    strength | ( Map: India )

Bioequivalence Study Bevacizumab Biosimilar (BEVZ92) Versus Bevacizumab (AVASTIN®) in First-line Treatment mCRC Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02069704
Recruitment Status : Completed
First Posted : February 24, 2014
Results First Posted : July 23, 2019
Last Update Posted : July 23, 2019
Sponsor:
Collaborators:
Laboratorio Elea S.A.C.I.F. y A.
Libbs Farmacêutica LTDA
Information provided by (Responsible Party):
mAbxience S.A

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Colorectal Cancer (mCRC)
Interventions Drug: Bevacizumab biosimilar (BEVZ92)
Drug: Avastin® (bevacizumab, reference product)
Enrollment 142
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product)
Hide Arm/Group Description Bevacizumab biosimilar (BEVZ92): Bevacizumab biosimilar (BEVZ92), Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Avastin® (bevacizumab, reference product): Avastin® (bevacizumab, reference product).

Active ingredient: Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to administration of chemotherapy (Folfox any or Folfiri).

Period Title: Overall Study
Started 69 [1] 71
Completed 69 71
Not Completed 0 0
[1]
Two patients were randomized but they did not received study treatment
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product) Total
Hide Arm/Group Description Bevacizumab biosimilar (BEVZ92): Bevacizumab biosimilar (BEVZ92), Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Avastin® (bevacizumab, reference product): Avastin® (bevacizumab, reference product).

Active ingredient: Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to administration of chemotherapy (Folfox any or Folfiri).

Total of all reporting groups
Overall Number of Baseline Participants 69 71 140
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 69 participants 71 participants 140 participants
56.3  (12.9) 56.7  (11.6) 56.5  (12.2)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Aged Number Analyzed 69 participants 71 participants 140 participants
< 65 years
49
  71.0%
51
  71.8%
100
  71.4%
>= 65 years
20
  29.0%
20
  28.2%
40
  28.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 71 participants 140 participants
Female
30
  43.5%
32
  45.1%
62
  44.3%
Male
39
  56.5%
39
  54.9%
78
  55.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 69 participants 71 participants 140 participants
White
50
  72.5%
55
  77.5%
105
  75.0%
Asian
14
  20.3%
12
  16.9%
26
  18.6%
Black
2
   2.9%
3
   4.2%
5
   3.6%
Other
3
   4.3%
1
   1.4%
4
   2.9%
Eastern Cooperative Oncology Group (ECOG) performance status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 71 participants 140 participants
0
7
  10.1%
18
  25.4%
25
  17.9%
1
57
  82.6%
43
  60.6%
100
  71.4%
2
5
   7.2%
10
  14.1%
15
  10.7%
[1]
Measure Description:

Describes a patient’s ability to selfcare, daily activity and physical ability. Grades:

0. Fully active, able to carry on all pre-disease performance without restriction.

  1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.
  2. Ambulatory and capable of all selfcare but unable to carry out any work activities; about >50% of waking hours.
  3. Capable of only limited selfcare; confined to bed or chair >50% of waking hours.
  4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair.
  5. Dead.
Tumor, lymph Nodes and Metastases (TNM) stage   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 71 participants 140 participants
IVa
30
  43.5%
32
  45.1%
62
  44.3%
IVb
38
  55.1%
38
  53.5%
76
  54.3%
missing
1
   1.4%
1
   1.4%
2
   1.4%
[1]
Measure Description:

The TNM Classification of Malignant Tumors describes the stage of a solid tumor according to:

  1. Primary tumour (T)- the size and whether it has invaded nearby tissue, from 0 [no evidence of tumor] to 4 [the highest size and/or extension]
  2. Lymph nodes (N) describes nearby (regional) lymph nodes that are involved, from 0 [no evidence of tumor] to 3 [high extension and numerous lymph nodes],
  3. Metastasis (M) describes distant metastasis, from 0 (no metastases) to 1 (yes). Stage IVa: Any T, Any N, M1a (to the other lung); Stage IVb: Any T, Any N, M1b or M1c ( outside of the chest)
Months since diagnosis of metastatic colorectal cancer   [1] 
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 67 participants 69 participants 136 participants
13.0  (14.7) 13.0  (17.5) 13.0  (16.1)
[1]
Measure Analysis Population Description: Missing data for two patients in each treatment arm
Number of target lesions  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 71 participants 140 participants
1
9
  13.0%
11
  15.5%
20
  14.3%
2
29
  42.0%
31
  43.7%
60
  42.9%
>=3
31
  44.9%
29
  40.8%
60
  42.9%
Extent of disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 71 participants 140 participants
Liver disease only
7
  10.1%
5
   7.0%
12
   8.6%
Other
62
  89.9%
66
  93.0%
128
  91.4%
Previous treatment  
Measure Type: Number
Unit of measure:  Participants
Surgery Number Analyzed 69 participants 71 participants 140 participants
55 53 108
Radiotherapy Number Analyzed 69 participants 71 participants 140 participants
14 15 29
Chemotherapy Number Analyzed 69 participants 71 participants 140 participants
24 23 47
1.Primary Outcome
Title Area Under the Concentration-versus-time Curve (AUC) at Cycle 1 (AUC0-336h) of BEVZ92 and Avastin®
Hide Description

To compare the pharmacokinetic (PK) profile of BEVZ92 and Avastin®, both administered in combination with FOLFOX (any) or FOLFIRI, by means of comparing the truncated AUC calculated from start of the first infusion until start of the second infusion (i.e. at Cycle 1; AUC0–336h)

For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio of a log-transformed exposure measure (AUC) falls completely within the range 80–125%.

Time Frame AUC0-336 hrs: 0 to 336 hours after start of the first infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Overall number of participants Analyzed equals to number of subjects who contributed to summary statistics.
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product).
Hide Arm/Group Description:
Bevacizumab proposed biosimilar (BEVZ92)
Avastin® (bevacizumab, reference product).
Overall Number of Participants Analyzed 55 61
Geometric Least Squares Mean (Geometric Coefficient of Variation)
Unit of Measure: ng.h/mL
16500000
(30.7%)
16600000
(31.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab Biosimilar (BEVZ92), Avastin® (Bevacizumab, Ref. Product).
Comments Based on previously published PK data for reference bevacizumab in metastatic colorectal cancer, we assumed a conservative inter-participant coefficient of variation for AUC of around 35%. A sample size of 51 patients in each treatment arm could show bioequivalence with a nominal power of 90% and an α of 0·05, if the 90% CIs for the ratio of BEVZ92 to reference bevacizumab of the geometric means for AUC0–336h and AUCss were within the acceptance interval of 80%–125%.
Type of Statistical Test Equivalence
Comments Two treatments are judged not to be different from one another if the 90% CI of the ratio of a log-transformed exposure measure (AUC) falls completely within the range 80%–125%.
Method of Estimation Estimation Parameter ratio BEVZ92 to Avastin
Estimated Value 99.4
Confidence Interval (2-Sided) 90%
90.5 to 109.0
Estimation Comments For the ratio: BEVZ92 represents the numerator and reference bevacizumab the denominator
2.Primary Outcome
Title AUC at Steady State (AUCss) of BEVZ92 and Avastin®
Hide Description

To compare the PK profile of BEVZ92 and Avastin®, both administered in combination with FOLFOX (any) or FOLFIRI, by means of comparing the truncated area under the concentration-versus-time curve calculated over a dosage interval at steady state (i.e. at Cycle 7; AUCss).

For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% CI of the ratio of a log-transformed exposure measure (AUC) falls completely within the range 80–125%.

Time Frame AUCss: 0 to 336 hours after the administration of Cycle 7 infusion (Week 13).
Hide Outcome Measure Data
Hide Analysis Population Description
In the Avastin arm there were 3 missing samples at the timepoint required for the specific PK parameters within Cycle 7.
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product).
Hide Arm/Group Description:

Bevacizumab proposed biosimilar (BEVZ92):

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Bevacizumab reference product: Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).
Overall Number of Participants Analyzed 55 58
Geometric Least Squares Mean (Geometric Coefficient of Variation)
Unit of Measure: ng.h/mL
35900000
(34.8%)
35700000
(36.6%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab Biosimilar (BEVZ92), Avastin® (Bevacizumab, Ref. Product).
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments Two treatments are judged not to be different from one another if the 90% CI of the ratio of a log-transformed exposure measure (AUC) falls completely within the range 80%–125%.
Method of Estimation Estimation Parameter ratio BEVZ92 to Avastin
Estimated Value 100.0
Confidence Interval (2-Sided) 90%
90.2 to 112.0
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Reported With BEVZ92 and Avastin®
Hide Description Compare the safety profile by means of the frequency and severity of TEAEs and SAEs reported in each treatment arm.
Time Frame From first study dose and up to 30 days after the end of study treatment for each patient, for an average of 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
All patients receiving at least one dose of study medication.
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product)
Hide Arm/Group Description:

Bevacizumab 25 mg/mL (strength: 100 mg/4 mL).

Bevacizumab biosimilar (BEVZ92): Bevacizumab biosimilar (BEVZ92), Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Bevacizumab 25mg/ml (strength: 100mg/4ml)

Avastin® (bevacizumab, reference product): Avastin® (bevacizumab, reference product). Active ingredient: Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to administration of chemotherapy (Folfox any or Folfiri).

Overall Number of Participants Analyzed 69 71
Measure Type: Number
Unit of Measure: participants
Any TEAE (any causality) 66 71
Any grade>=3 TEAE 44 49
Any TEAE leading to discontinuation 13 6
Any treatment-related TEAE 63 70
Any grade >=3 treatment-related TEAE 63 70
Any serious TEAE 19 21
Any bleeding event 14 19
4.Secondary Outcome
Title Anti-Drug Antibody (ADA) of BEVZ92 and Avastin®
Hide Description Immunogenicity profile by means of measurement of ADA developed de novo (seroconversion) after cycle 5, cycle 8, and 12 months after first drug administration (pre-dose).
Time Frame At baseline, and on Day 1 (pre-dose) of Cycles: 1, 5 and 8, and 12 months after first drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
All patients receiving at least one dose of study medication.
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product)
Hide Arm/Group Description:

Bevacizumab 25 mg/mL (strength: 100 mg/4 mL).

Bevacizumab biosimilar (BEVZ92): Bevacizumab biosimilar (BEVZ92), Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Bevacizumab 25mg/ml (strength: 100mg/4ml)

Avastin® (bevacizumab, reference product): Avastin® (bevacizumab, reference product).

Active ingredient: Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to administration of chemotherapy (Folfox any or Folfiri).

Overall Number of Participants Analyzed 69 71
Measure Type: Number
Unit of Measure: participants
Seroconversion 2 0
No seroconversion 67 71
5.Secondary Outcome
Title Objective Response Rate (ORR) of BEVZ92 and Avastin®
Hide Description

To compare efficacy in terms of ORR between arms. Clinical and radiological tumor assessments were performed according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 using computed tomography (CT) or magnetic resonance imaging (MRI) scans.

Objective response (OR) is defined as a best overall response of partial response (PR) or complete response (CR) as defined by RECIST v1.1. All participants who did not meet the criteria for CR or PR by the end of the study were considered non-responders.

Time Frame Every four weeks. Up to 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product)
Hide Arm/Group Description:

Bevacizumab 25 mg/mL (strength: 100 mg/4 mL).

Bevacizumab biosimilar (BEVZ92): Bevacizumab biosimilar (BEVZ92), Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Bevacizumab 25mg/ml (strength: 100mg/4ml)

Avastin® (bevacizumab, reference product): Avastin® (bevacizumab, reference product). Active ingredient: Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to administration of chemotherapy (Folfox any or Folfiri).

Overall Number of Participants Analyzed 71 71
Measure Type: Count of Participants
Unit of Measure: Participants
ORR (CR+PR)
35
  49.3%
40
  56.3%
Stable disease
27
  38.0%
25
  35.2%
Progressive disease
4
   5.6%
2
   2.8%
unevaluable
5
   7.0%
4
   5.6%
6.Secondary Outcome
Title Cmax,sd of BEVZ92 and Avastin®
Hide Description Secondary PK endpoints included the Cmax calculated at Cycle 1 (Cmax,sd )
Time Frame Cmax, sd: 0 to 336 hours after start of the first infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Overall number of participants Analyzed equals to number of subjects who contributed to summary statistics.
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product).
Hide Arm/Group Description:

Bevacizumab proposed biosimilar (BEVZ92):

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Bevacizumab reference product:

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Overall Number of Participants Analyzed 55 61
Geometric Least Squares Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
120000
(30%)
123000
(27.2%)
7.Secondary Outcome
Title Progression-free Survival (PFS) of BEVZ92 and Avastin®
Hide Description Compare PFS between the randomized treatment arms. Progression-free survival (PFS) was defined as the time from the randomization date to the date of disease progression using RECIST v1.1, or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions plus 5 mm absolute increase, and/or unequivocal progression of known non-target lesion, and/or the appearance of new lesions".
Time Frame From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product)
Hide Arm/Group Description:

Bevacizumab proposed biosimilar (BEVZ92):

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Bevacizumab reference product:

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Overall Number of Participants Analyzed 71 71
Median (95% Confidence Interval)
Unit of Measure: months
10.8
(7.4 to 11.5)
11.1
(8.6 to 12.8)
8.Secondary Outcome
Title Cmax,ss of BEVZ92 and Avastin®
Hide Description Secondary PK endpoints included the Cmax calculated at Cycle 7 (Cmax, ss )
Time Frame Cmax, ss: 0 to 336 hours post-dose after the administration of Cycle 7 infusion (Week 13)
Hide Outcome Measure Data
Hide Analysis Population Description
In the Avastin arm there were 3 missing samples at the timepoint required for the specific PK parameter within Cycle 7.
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product).
Hide Arm/Group Description:

Bevacizumab proposed biosimilar (BEVZ92):

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Bevacizumab reference product:

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Overall Number of Participants Analyzed 55 58
Geometric Least Squares Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
195000
(29.5%)
200000
(30.7%)
9.Secondary Outcome
Title Ctrough,sd of BEVZ92 and Avastin®
Hide Description Secondary PK endpoints included the Ctrough calculated at Cycle 1 (Ctrough,sd )
Time Frame Ctrough, sd: 0 to 336 hours after start of the first infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
In the Avastin arm there was 1 missing samples at the timepoint required for the specific PK parameter within Cycle 1.
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product).
Hide Arm/Group Description:

Bevacizumab proposed biosimilar (BEVZ92):

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Bevacizumab reference product:

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Overall Number of Participants Analyzed 55 60
Geometric Least Squares Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
344
(12.5%)
349
(13.7%)
10.Secondary Outcome
Title Ctrough,ss of BEVZ92 and Avastin®
Hide Description Secondary PK endpoints included the Ctrough calculated at Cycle 7 (Ctrough,ss)
Time Frame Ctrough, ss: 0 to 336 hours after the administration of the Cycle 7 infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
There were 4 missing samples (1 in the BEVZ92 and 3 in the Avastin arm) at the timepoint required for the specific PK parameter within Cycle 7.
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product).
Hide Arm/Group Description:

Bevacizumab proposed biosimilar (BEVZ92):

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Bevacizumab reference product:

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Overall Number of Participants Analyzed 54 58
Geometric Least Squares Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
69600
(52.1%)
69300
(50.5%)
11.Secondary Outcome
Title Elimination Half-life (t1/2) of BEVZ92 and Avastin®
Hide Description Secondary PK endpoints included the t1/2 calculated at Cycle 7
Time Frame t1/2: 0 to 336 hours after the administration of the Cycle 7 infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
In the Avastin arm there were several missing samples at the timepoint required for the specific PK parameter
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product).
Hide Arm/Group Description:

Bevacizumab proposed biosimilar (BEVZ92):

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Bevacizumab reference product:

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Overall Number of Participants Analyzed 49 52
Geometric Least Squares Mean (Geometric Coefficient of Variation)
Unit of Measure: h
294
(33.3%)
289
(32.8%)
12.Secondary Outcome
Title Elimination Rate Constant (Kel) of BEVZ92 and Avastin®
Hide Description Secondary PK endpoints included the Kel calculated at Cycle 7 (Ctrough,ss)
Time Frame Kel: 0 to 336 hours after the administration of the Cycle 7 infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Overall number of participants Analyzed equals to number of subjects who contributed to summary statistics.
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product).
Hide Arm/Group Description:

Bevacizumab proposed biosimilar (BEVZ92):

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Bevacizumab reference product:

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Overall Number of Participants Analyzed 55 61
Geometric Least Squares Mean (Geometric Coefficient of Variation)
Unit of Measure: l/h
0.00236
(33.3%)
0.00240
(32.8%)
13.Secondary Outcome
Title Volume of Distribution (Vd) of BEVZ92 and Avastin®
Hide Description Secondary PK endpoints included the Vd calculated at Cycle 7
Time Frame Vd: 0 to 336 hours after the administration of the Cycle 7 infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
In the Avastin arm there were several missing samples at the timepoint required for the specific PK parameter
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product).
Hide Arm/Group Description:

Bevacizumab proposed biosimilar (BEVZ92):

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Bevacizumab reference product:

Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Overall Number of Participants Analyzed 49 52
Geometric Least Squares Mean (Geometric Coefficient of Variation)
Unit of Measure: L
4.06
(37.7%)
3.86
(39.4%)
Time Frame Throughout the study (on day 1 of every cycle and 30 days after the end of study treatment). Adverse event data were collected from the beginning of the study at 29 Oct 2014 till last patient last visit in 10 Dec 2017 (Database lock point).
Adverse Event Reporting Description Coded according to Medical Dictionary for Regulatory Activities (version 16.0), and graded on the basis of the US National Cancer Institute’s Common Terminology for Adverse Events (version 4.0).
 
Arm/Group Title Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product)
Hide Arm/Group Description Bevacizumab biosimilar (BEVZ92): Bevacizumab biosimilar (BEVZ92), Active ingredient Bevacizumab 25 mg/mL (strength = 100mg/mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to chemotherapy (Folfox any or Folfiri).

Avastin® (bevacizumab, reference product): Avastin® (bevacizumab, reference product).

Active ingredient: Bevacizumab 25 mg/mL (strength: 100 mg/4 mL). 30-minute* IV infusion (5 mg/kg) every 2 weeks, prior to administration of chemotherapy (Folfox any or Folfiri).

All-Cause Mortality
Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product)
Affected / at Risk (%) Affected / at Risk (%)
Total   11/69 (15.94%)      7/71 (9.86%)    
Show Serious Adverse Events Hide Serious Adverse Events
Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/69 (27.54%)      21/71 (29.58%)    
Blood and lymphatic system disorders     
Neutropenia  1  1/69 (1.45%)  1 4/71 (5.63%)  6
Anemia  1  1/69 (1.45%)  1 3/71 (4.23%)  4
Leukopenia  1  0/69 (0.00%)  0 2/71 (2.82%)  2
Disseminated intravascular coagulation  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Febrile neutropenia  1  1/69 (1.45%)  1 1/71 (1.41%)  2
Thrombocytopenia  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Cardiac disorders     
Cardiac failure acute  1  1/69 (1.45%)  1 1/71 (1.41%)  1
Eye disorders     
Eye hemorrhage  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Gastrointestinal disorders     
Diarrhea  1  1/69 (1.45%)  1 4/71 (5.63%)  5
Constipation  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Enteritis  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Intestinal obstruction  1  5/69 (7.25%)  6 0/71 (0.00%)  0
Ileus paralytic  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Abdominal pain  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Lower Gastrointestinal hemorrhage  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Large intestine perforation  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Subileus  1  0/69 (0.00%)  0 1/71 (1.41%)  1
General disorders     
Death  1 [1]  1/69 (1.45%)  1 0/71 (0.00%)  0
General physical health deterioration  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Multi- organ failure  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Sudden death  1 [1]  1/69 (1.45%)  1 0/71 (0.00%)  0
Hepatobiliary disorders     
Cholecystis acute  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Immune system disorders     
Anaphylactic reaction  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Infections and infestations     
Bronchopneumonia  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Sepsis  1  1/69 (1.45%)  1 3/71 (4.23%)  3
Urinary tract infection  1  1/69 (1.45%)  1 2/71 (2.82%)  2
Catheter site abscess  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Oral candidiasis  1  1/69 (1.45%)  1 1/71 (1.41%)  1
Peritonitis  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Septic shock  1  1/69 (1.45%)  1 1/71 (1.41%)  1
Diarrhea infectious  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Pelvic Abscess  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Pneumonia  1  1/69 (1.45%)  1 1/71 (1.41%)  1
Injury, poisoning and procedural complications     
Ankle fracture  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Infusion Related Reaction  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Subdural hematoma  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Excoriation  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Investigations     
Transaminases increased  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Metabolism and nutrition disorders     
Hypernatremia  1  1/69 (1.45%)  1 1/71 (1.41%)  1
Hypoalbuminemia  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Hypokalemia  1  0/69 (0.00%)  0 1/71 (1.41%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumor hemorrhage  1  0/69 (0.00%)  0 2/71 (2.82%)  2
Nervous system disorders     
Monoparesis  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Paresthesia  1  1/69 (1.45%)  1 1/71 (1.41%)  1
Dystonia  1  0/69 (0.00%)  0 1/71 (1.41%)  1
Renal and urinary disorders     
Acute Kidney injury  1  1/69 (1.45%)  1 1/71 (1.41%)  1
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Pneumonitis  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Vascular disorders     
Embolism  1  1/69 (1.45%)  1 0/71 (0.00%)  0
Hypotension  1  0/69 (0.00%)  0 2/71 (2.82%)  2
Vena Cava Thrombosis  1  0/69 (0.00%)  0 1/71 (1.41%)  1
1
Term from vocabulary, MedDRA (16.0)
Indicates events were collected by systematic assessment
[1]
Included in All-cause mortality
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bevacizumab Biosimilar (BEVZ92) Avastin® (Bevacizumab, Ref. Product)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   66/69 (95.65%)      71/71 (100.00%)    
Blood and lymphatic system disorders     
Neutropenia  1  23/69 (33.33%)  26/71 (36.62%) 
Anemia  1  19/69 (27.54%)  28/71 (39.44%) 
Leukopenia  1  14/69 (20.29%)  16/71 (22.54%) 
Thrombocytopenia  1  10/69 (14.49%)  13/71 (18.31%) 
Gastrointestinal disorders     
Diarrhea  1  34/69 (49.28%)  41/71 (57.75%) 
Nausea  1  31/69 (44.93%)  32/71 (45.07%) 
Vomiting  1  25/69 (36.23%)  24/71 (33.80%) 
Constipation  1  9/69 (13.04%)  19/71 (26.76%) 
Abdominal pain  1  6/69 (8.70%)  18/71 (25.35%) 
Stomatitis  1  9/69 (13.04%)  8/71 (11.27%) 
Abdominal pain upper  1  5/69 (7.25%)  5/71 (7.04%) 
Intestinal obstruction  1  5/69 (7.25%)  1/71 (1.41%) 
Proctalgia  1  5/69 (7.25%)  1/71 (1.41%) 
Dyspepsia  1  4/69 (5.80%)  4/71 (5.63%) 
Rectal hemorrhage  1  4/69 (5.80%)  1/71 (1.41%) 
General disorders     
Asthenia  1  22/69 (31.88%)  21/71 (29.58%) 
Fatigue  1  16/69 (23.19%)  18/71 (25.35%) 
Pyrexia  1  6/69 (8.70%)  14/71 (19.72%) 
Mucosal inflammation  1  7/69 (10.14%)  6/71 (8.45%) 
Edema peripheral  1  3/69 (4.35%)  6/71 (8.45%) 
Infections and infestations     
Urinary tract infection  1  7/69 (10.14%)  6/71 (8.45%) 
Upper respiratory tract infection  1  6/69 (8.70%)  6/71 (8.45%) 
Influenza  1  6/69 (8.70%)  5/71 (7.04%) 
Respiratory tract infection viral  1  4/69 (5.80%)  3/71 (4.23%) 
Viral upper respiratory tract infection  1  4/69 (5.80%)  1/71 (1.41%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  2/69 (2.90%)  4/71 (5.63%) 
Investigations     
Weight decreased  1  16/69 (23.19%)  12/71 (16.90%) 
Alanine aminotransferase increased  1  8/69 (11.59%)  9/71 (12.68%) 
Aspartate aminotransferase increased  1  4/69 (5.80%)  10/71 (14.08%) 
Blood creatinine increased  1  2/69 (2.90%)  6/71 (8.45%) 
Blood alkaline phosphatase increased  1  2/69 (2.90%)  5/71 (7.04%) 
Metabolism and nutrition disorders     
Decreased appetite  1  19/69 (27.54%)  20/71 (28.17%) 
Hypertriglyceridemia  1  11/69 (15.94%)  17/71 (23.94%) 
Hyperkalemia  1  4/69 (5.80%)  8/71 (11.27%) 
Hyperglycemia  1  3/69 (4.35%)  10/71 (14.08%) 
Hypercholesterolaemia  1  5/69 (7.25%)  5/71 (7.04%) 
Hypernatraemia  1  4/69 (5.80%)  1/71 (1.41%) 
Hypocalcaemia  1  3/69 (4.35%)  4/71 (5.63%) 
Hypokalemia  1  1/69 (1.45%)  4/71 (5.63%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  6/69 (8.70%)  5/71 (7.04%) 
Pain in extremity  1  6/69 (8.70%)  5/71 (7.04%) 
Arthralgia  1  1/69 (1.45%)  5/71 (7.04%) 
Nervous system disorders     
Neuropathy peripheral  1  13/69 (18.84%)  13/71 (18.31%) 
Peripheral sensory neuropathy  1  11/69 (15.94%)  16/71 (22.54%) 
Paresthesia  1  10/69 (14.49%)  10/71 (14.08%) 
Headache  1  7/69 (10.14%)  10/71 (14.08%) 
Dysgeusia  1  4/69 (5.80%)  12/71 (16.90%) 
Dizziness  1  4/69 (5.80%)  4/71 (5.63%) 
Dysesthesia  1  3/69 (4.35%)  4/71 (5.63%) 
Renal and urinary disorders     
Proteinuria  1  7/69 (10.14%)  5/71 (7.04%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  7/69 (10.14%)  11/71 (15.49%) 
Cough  1  4/69 (5.80%)  9/71 (12.68%) 
Dysaesthesia pharynx  1  5/69 (7.25%)  2/71 (2.82%) 
Dysphonia  1  0/69 (0.00%)  5/71 (7.04%) 
Productive cough  1  0/69 (0.00%)  5/71 (7.04%) 
Skin and subcutaneous tissue disorders     
Skin hyperpigmentation  1  7/69 (10.14%)  7/71 (9.86%) 
Alopecia  1  5/69 (7.25%)  2/71 (2.82%) 
Palmar-plantar erythrodysaesthesia syndrome  1  4/69 (5.80%)  8/71 (11.27%) 
Pruritus  1  3/69 (4.35%)  4/71 (5.63%) 
Vascular disorders     
Hypertension  1  17/69 (24.64%)  20/71 (28.17%) 
1
Term from vocabulary, MedDRA (16.0)
Indicates events were collected by systematic assessment
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: Susana Millan
Organization: mAbxience
Phone: +34917711500
EMail: susana.millan@mabxience.com
Layout table for additonal information
Responsible Party: mAbxience S.A
ClinicalTrials.gov Identifier: NCT02069704     History of Changes
Other Study ID Numbers: BEVZ92-A-01-13
BEVZ92-A-01-13 ( Registry Identifier: BEVZ92-A-01-13 )
First Submitted: February 14, 2014
First Posted: February 24, 2014
Results First Submitted: December 3, 2018
Results First Posted: July 23, 2019
Last Update Posted: July 23, 2019