A Safety and Efficacy Study of BCD-022 With Paclitaxel Co... | NCT01764022

NCT01764022

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BCD-022	Experimental	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Drug: Trastuzumab Drug: Paclitaxel
Herceptin®	Active Comparator	In this arm patients will receive 6 courses of treatment with Herceptin® (F. Hoffmann-La Roche Ltd., Switzerland) in combination with paclitaxel. Patients will receive Herceptin® at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	Drug: Trastuzumab Drug: Paclitaxel

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Trastuzumab	Drug	Patients will receive 6 courses of trastuzumab in combination with paclitaxel. Trastuzumab will be administered at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations) as 90 min intravenous infusion every 3 weeks (on Day 1 of each cycle).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Response Rate	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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. The response was assessed at the screening, after 3 therapy cycles and after 6 therapy cycles. If CT after 3 or 6 therapy cycles revealed the complete or partial response, a confirmatory CT scan was performed 4 weeks later. The best response during the study was assessed.	Day 127
Area Under the Curve After the First Test Drug Administration	Primary outcome measure for pharmacokinetics (PK) substudy. AUC(0-504) of trastuzumab in HER2(+) mBC patients after first administration of BCD-022 with paclitaxel or Herceptin® with paclitaxel.	up to Day 22, after the first trastuzumab 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	Description	Time Frame
Complete Response Rate	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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. The response was assessed at the screening, after 3 therapy cycles and after 6 therapy cycles. If CT after 3 or 6 therapy cycles revealed the complete or partial response, a confirmatory CT scan was performed 4 weeks later. The best response during the study was assessed.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Written informed consent and ability to follow the Protocol procedures;
Age from 18 years to 75 years inclusive;
Female gender;
Histologically confirmed breast cancer (BC);
Metastatic BC (stage IV according to TNM classification version 6);
Grade 3+ HER2 overexpression confirmed by immunohistochemical (IHC) staining or grade 2+ HER2 overexpression accompanied by HER2 gene amplification confirmed by fluorescent hybridization in situ (FISH) ;
Documented results of oestrogen and progesterone receptors expression analysis;
Eastern Cooperative Oncology Group (ECOG) status 0, 1 or 2, not increasing within 2 weeks prior to randomization;
Life expectancy - 20 weeks or more from the moment of randomization;
Presence of at least 1 tumour with a size not less than 1 cm (revealed with computed tomography (CT) slice thickness not more than 5 mm). Patients having bone metastasis as the only measurable tumour are not eligible for the trial;
Patients of childbearing potential must implement reliable contraceptive measures during the study treatment, starting 4 weeks prior to inclusion into the trial and until 6 months after the last administration of the study drug.

Exclusion Criteria:

Previous anticancer therapy for metastatic BC, including cytotoxic chemotherapy, or previous anticancer therapy with signal transduction inhibitors (e.g. lapatinib), biological drugs (e.g. trastuzumab, bevacizumab), experimental (not approved for BC therapy) anticancer drugs. Any previous hormonal therapy is allowed;
Disease progression within 6 months after adjuvant and/or neoadjuvant anti BC therapy;
Surgery, radiation therapy, use of any experimental medications within 4 weeks (28 days) prior to randomization;
Hypersensitivity to paclitaxel and all medications containing polyoxyethylated castor oil, hypersensitivity to dexamethasone, diphenhydramine, ranitidine/cimetidine, recombinant murine proteins, contrast agents or excipients of study medications;
BC metastases in central nervous system, progressing or clinically manifested (e.g. cerebral oedema, spinal cord injury), with exception of non-progressing metastases not requiring treatment with glucocorticosteroids and/or anticonvulsants within 4 weeks prior to randomization;
Cardiovascular system pathology (congestive heart failure (CHF) stage III-IV according to New York Heart Association (NYHA) classification, unstable angina pectoris, myocardial infarction) within 12 months prior to randomization;
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-medicamental correction methods (low salt diet, physical exercise);
Left ventricular ejection fraction <50% according to electrocardiography;
Neutrophils ≤1500/mm3;
Platelets ≤100 000/mm3;
Hemoglobin ≤90 g/L;
Creatinine level ≥ 1.5 × upper limit of normal (ULN);
Bilirubin level ≥ 1.5 × ULN;
Asparagine transferase (AST) and alanine transferase (ALT) levels ≥ 2.5 × ULN (5 × ULN for patients with liver metastases);
Alkaline phosphatase level ≥ 5 × ULN;
Pregnancy or lactation;
Any other concomitant cancer including contralateral breast 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;
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;
Concomitant 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;
Acute or active chronic infections;
Hepatitis C virus, hepatitis B virus, HIV or syphilis infections;
Obstacles in intravenous administration of study drugs

Contacts/Locations Module

Name	Affiliation	Role
Roman Ivanov, MD, PhD	Vice-president, R&D	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Brest Region Clinical Oncology Dispensary		Brest			Belarus
Grodno Regional Hospital

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32819305	Derived	Alexeev SM, Khorinko AV, Mukhametshina GZ, Shelepen KG, Burdaeva ON, Kulik SA, Satheesh CT, Srivastava K, Vikranth M, Kryukov F, Paltusova AN, Shustova MS, Ivanov RA. Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab. BMC Cancer. 2020 Aug 20;20(1):783. doi: 10.1186/s12885-020-07247-9.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

223 of 225 randomized patients received at least one BCD-022 or Herceptin® injection. 2 patients were excluded prior to first drug administration. Patients who do not received at least one study drug administration were not included to any analysis.

Arm/Group Information

ID	Title	Description
BG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
BG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00050.687± 10.948 BG00150.573± 9.877 BG00250.63± 10.415

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000115 BG001110 BG002

HER2 Expression

Count of Participants

Participants

Title

Denominators

Categories

HER2 +++

Title	Measurements
	BG000100 BG00197 BG002

Histologic type of cancer

Count of Participants

Participants

Title

Denominators

Categories

Ductal

Title	Measurements
	BG00036 BG00133 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Response Rate

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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.

The response was assessed at the screening, after 3 therapy cycles and after 6 therapy cycles. If CT after 3 or 6 therapy cycles revealed the complete or partial response, a confirmatory CT scan was performed 4 weeks later. The best response during the study was assessed.

The population for efficacy analysis included patients who received at least one injection of study drug and had evaluable results of treatment.

Posted

Count of Participants

Participants

Day 127

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Units	Counts
Participants	OG000113 OG001110

Title

Denominators

Categories

Title	Measurements
	OG00056 OG00148

Primary

Area Under the Curve After the First Test Drug Administration

Primary outcome measure for pharmacokinetics (PK) substudy. AUC(0-504) of trastuzumab in HER2(+) mBC patients after first administration of BCD-022 with paclitaxel or Herceptin® with paclitaxel.

Patients who received one dose of study drug and after 504 hours after the injection had missed <= 1 blood sample collection to analyse pharmacokinetics.

Posted

Median

Inter-Quartile Range

(ng/ml)*hour

up to Day 22, after the first trastuzumab 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)

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Secondary

Complete Response Rate

The population for efficacy analysis included patients who received at least one injection of study drug and had evaluable results of treatment.

Posted

Count of Participants

Participants

Day 127

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Secondary

Partial Response Rate

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.

The population for efficacy analysis included patients who received at least one injection of study drug and had evaluable results of treatment.

Posted

Count of Participants

Participants

Day 127

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Secondary

Stabilization Rate

The population for efficacy analysis included patients who received at least one injection of study drug and had evaluable results of treatment.

Posted

Count of Participants

Participants

Day 127

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Secondary

Progression Rate

The population for efficacy analysis included patients who received at least one injection of study drug and had evaluable results of treatment.

Posted

Count of Participants

Participants

Day 127

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Secondary

Treatment Postponed Due to AE/SAE

Secondary outcome measure for safety evaluation

Patients who received at least one injection of study drug.

Posted

Number

participants

Day 127

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Units	Counts
Participants

Secondary

Treatment Discontinuation Due to AE/SAE

Secondary outcome measure for safety evaluation

Patients who received at least one injection of study drug.

Posted

Number

participants

Day 127

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Units	Counts
Participants

Secondary

Occurrence of Neutralizing Anti-trastuzumab Antibodies

Secondary outcome measure for immunogenicity assessment. Patient was suggested as NAB-positive if neutralizing anti-trastuzumab antibodies were detected at any of the specified timepoints. Total number of NAB-positive patients in each are presented.

Patients who received at least one injection of study drug

Posted

Number

participants

Day 1 (before the drug administration), Day 14, 64, 127 and 154

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Secondary

Cmax After the First Test Drug Administration

Secondary outcome measure for PK substudy. Peak serum concentration of trastuzumab after single administration of BCD-022 + paclitaxel or Herceptin® + paclitaxel

Patients who received one dose of study drug and after 504 hours after the injection had missed <= 1 blood sample collection to analyse pharmacokinetics.

Posted

Median

Inter-Quartile Range

ng/ml

Up to Day 22

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Secondary

Tmax After the First Test Drug Administration

Secondary outcome measure for PK substudy. Time to reach peak serum concentration of trastuzumab after the first administration of BCD-022 + paclitaxel or Herceptin® + paclitaxel

Patients who received one dose of study drug and after 504 hours after the injection had missed <= 1 blood sample collection to analyse pharmacokinetics.

Posted

Median

Inter-Quartile Range

hours

Up to Day 22

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Secondary

T1/2 After the First Test Drug Administration

Secondary outcome measure for PK substudy. Half-life period of trastuzumab after the first administration of BCD-022 + paclitaxel or Herceptin® + paclitaxel.

Patients who received one dose of study drug and after 504 hours after the injection had missed <= 1 blood sample collection to analyse pharmacokinetics.

Posted

Median

Inter-Quartile Range

hours

Up to Day 22

ID	Title	Description
OG000	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Secondary

Cmax After the Sixth Test Drug Administration

Secondary outcome measure for PK substudy. Peak serum concentration of trastuzumab after the sixth administration of BCD-022 + paclitaxel or Herceptin® + paclitaxel.

Patients who received six dose of study drug and had missed <= 1 blood sample collection to analyse pharmacokinetics.

Posted

Median

Inter-Quartile Range

ng/ml

Up to Day 127

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Secondary

Tmax After the Sixth Test Drug Administration

Secondary outcome measure for PK substudy. Time to reach peak serum concentration of trastuzumab after the sixth administration of BCD-022 + paclitaxel or Herceptin® + paclitaxel

Patients who received six dose of study drug and had missed <= 1 blood sample collection to analyse pharmacokinetics.

Posted

Median

Inter-Quartile Range

hour

Up to Day 127

ID	Title	Description
OG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).
OG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	BCD-022 (CJSC BIOCAD)	BCD-022 is a product code for trastuzumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-022 in combination with paclitaxel. Patients will receive BCD-022 at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	3	113	8	113	106	113
EG001	Herceptin ® (F. Hoffmann-La Roche Ltd., Switzerland)	In this arm patients will receive 6 courses of treatment with Herceptin in combination with paclitaxel. Patients will receive Herceptin at a loading dose of 8 mg/kg (once), followed by maintenance dose of 6 mg/kg every 3 weeks (5 administrations), + paclitaxel 175 mg/m2 every 3 weeks as 3 hour intravenous infusion (6 administrations).	5	110	13	110	104	110

Serious Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Pneumonia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0001 affected113 at risk EG0010 affected110 at risk
Gastrointestinal hemorrhage	Gastrointestinal disorders	Systematic Assessment		EG0001 affected113 at risk EG0010 affected110 at risk
Disease progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	lethal outcome	EG0001 affected113 at risk EG0012 affected110 at risk
Death for unknown reason	General disorders	Systematic Assessment		EG0001 affected113 at risk EG0011 affected110 at risk
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment	lethal outcome	EG0000 affected113 at risk EG0011 affected110 at risk
Paroxism of atrial fibrillation	Cardiac disorders	Systematic Assessment		EG0000 affected113 at risk EG0012 affected110 at risk
Ventricular extrasystolone RYAN-1	Cardiac disorders	Systematic Assessment		EG0000 affected113 at risk EG0011 affected110 at risk
Anemia with trombocytopenia	Blood and lymphatic system disorders	Systematic Assessment		EG0000 affected113 at risk EG0011 affected110 at risk
Diarrhea with vomiting and weakness	General disorders	Systematic Assessment		EG0000 affected113 at risk EG0011 affected110 at risk
Neutropenic sepsis	Infections and infestations	Systematic Assessment	lethal outcome	EG0001 affected113 at risk EG0010 affected110 at risk
Pneumonitis with Septicemia	Infections and infestations	Systematic Assessment	lethal outcome	EG0000 affected113 at risk EG0011 affected110 at risk
Aspiration pneumonia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	lethal outcome	EG0000 affected113 at risk EG0011 affected110 at risk
Chest pain	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	unknown etiology	EG0001 affected113 at risk EG0010 affected110 at risk
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment		EG0001 affected113 at risk EG0011 affected110 at risk
Сervicitis	Reproductive system and breast disorders	Systematic Assessment		EG0001 affected113 at risk EG0010 affected110 at risk
Hepatic veins compression	Vascular disorders	Systematic Assessment		EG0000 affected113 at risk EG0011 affected110 at risk
Non-Neutropenic Fever	General disorders	Systematic Assessment	unknown etiology	EG0000 affected113 at risk EG0012 affected110 at risk
Bronchitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0000 affected113 at risk EG0011 affected110 at risk
Bronchopneumonia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0000 affected113 at risk EG0011 affected110 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Leucopenia	Blood and lymphatic system disorders	Systematic Assessment		EG00064 affected113 at risk EG00154 affected110 at risk
Leucocytosis	Blood and lymphatic system disorders	Systematic Assessment		EG00024 affected113 at risk EG00135 affected110 at risk
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment		EG00066 affected113 at risk EG00156 affected110 at risk
Anemia	Blood and lymphatic system disorders	Systematic Assessment		EG00075 affected113 at risk EG00173 affected110 at risk
Trombocytopenia	Blood and lymphatic system disorders	Systematic Assessment		EG00019 affected113 at risk EG00121 affected110 at risk
Elevated absolute neutrophil count	Blood and lymphatic system disorders	Systematic Assessment		EG00026 affected113 at risk EG00129 affected110 at risk
Elevated hemoglobin	Blood and lymphatic system disorders	Systematic Assessment		EG0006 affected113 at risk EG00111 affected110 at risk
Lymphopenia	Blood and lymphatic system disorders	Systematic Assessment		EG00053 affected113 at risk EG00140 affected110 at risk
Lymphocytosis	Blood and lymphatic system disorders	Systematic Assessment		EG00014 affected113 at risk EG00117 affected110 at risk
Erythropenia	Blood and lymphatic system disorders	Systematic Assessment		EG00026 affected113 at risk EG00125 affected110 at risk
Erythrocytosis	Blood and lymphatic system disorders	Systematic Assessment		EG00012 affected113 at risk EG00114 affected110 at risk
Trombocytosis	Blood and lymphatic system disorders	Systematic Assessment		EG00027 affected113 at risk EG00123 affected110 at risk
Hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment		EG00039 affected113 at risk EG00147 affected110 at risk
Hyperuricemia	Metabolism and nutrition disorders	Systematic Assessment		EG00019 affected113 at risk EG00124 affected110 at risk
Elevated alkaline phosphotase	Hepatobiliary disorders	Systematic Assessment		EG00028 affected113 at risk EG00127 affected110 at risk
Elevated AST	Hepatobiliary disorders	Systematic Assessment		EG00029 affected113 at risk EG00126 affected110 at risk
Elevated ALT	Hepatobiliary disorders	Systematic Assessment		EG00024 affected113 at risk EG00125 affected110 at risk
Alopecia	Skin and subcutaneous tissue disorders	Systematic Assessment		EG00026 affected113 at risk EG00126 affected110 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment		EG00011 affected113 at risk EG00111 affected110 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment		EG00015 affected113 at risk EG00110 affected110 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment		EG0007 affected113 at risk EG0015 affected110 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment		EG0006 affected113 at risk EG0015 affected110 at risk
Bradypnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG00015 affected113 at risk EG00113 affected110 at risk
Tachypnoea	Reproductive system and breast disorders	Systematic Assessment		EG0009 affected113 at risk EG0018 affected110 at risk
Neuropathy	Nervous system disorders	Systematic Assessment	non-specified	EG00013 affected113 at risk EG0019 affected110 at risk
Elevated urea	Renal and urinary disorders	Systematic Assessment		EG00011 affected113 at risk EG00113 affected110 at risk
Elevated creatinine	Renal and urinary disorders	Systematic Assessment		EG00016 affected113 at risk EG00114 affected110 at risk
Arterial hypertension	Vascular disorders	Systematic Assessment		EG00013 affected113 at risk EG00111 affected110 at risk
Tachycardia	Cardiac disorders	Systematic Assessment		EG00022 affected113 at risk EG00112 affected110 at risk
Fever	General disorders	Systematic Assessment		EG00016 affected113 at risk EG00114 affected110 at risk
Generalized weakness	General disorders	Systematic Assessment		EG00026 affected113 at risk EG00125 affected110 at risk
Elevated lactate degydrohenase	Investigations	Systematic Assessment		EG00034 affected113 at risk EG00132 affected110 at risk

ID	Term
D001943	Breast Neoplasms

ID	Term
D000068878	Trastuzumab
D017239	Paclitaxel

Ancestor Terms

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes

Units	Counts
Participants	OG000113 OG001110

Units	Counts
Participants	OG000107 OG001104

Units	Counts
Participants	OG000107 OG001104

Units	Counts
Participants	OG000104 OG001107

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases