Overview

This trial is active, not recruiting.

Condition her2-positive metastatic breast cancer
Treatments trastuzumab, paclitaxel
Phase phase 3
Targets HER, HER2
Sponsor Biocad
Start date October 2012
End date March 2015
Trial size 206 participants
Trial identifier NCT01764022, BCD-022-02

Summary

BCD-022-02 is a double-blind randomized clinical trial comparing efficacy of BCD-022 (INN: trastuzumab) and paclitaxel to Herceptin and paclitaxel in HER2-positive metastatic breast cancer with pharmacokinetics substudy. The purpose of the study is to demonstrate the non-inferiority of efficacy and safety of BCD-022 compared to Herceptin. Also study includes pharmacokinetics assessment.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(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).
trastuzumab BCD-022
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).
paclitaxel Taxacad
Paclitaxel will be administered at a dose of 175 mg/m2 every 3 weeks (on Day 1 of each course) as 3 hour intravenous infusion (6 courses totally).
(Active Comparator)
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).
trastuzumab BCD-022
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).
paclitaxel Taxacad
Paclitaxel will be administered at a dose of 175 mg/m2 every 3 weeks (on Day 1 of each course) as 3 hour intravenous infusion (6 courses totally).

Primary Outcomes

Measure
Overall response rate
time frame: Day 127
Area under the curve after the first test drug administration
time frame: 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
Complete response rate
time frame: Day 127
Partial response rate
time frame: Day 127
Stabilization rate
time frame: Day 127
Progression rate
time frame: Day 127
Relative number (%) of chemotherapy cycles, postponed due to adverse events (AE)
time frame: Day 127
Treatment discontinuation rate due to AE
time frame: Day 127
AE incidence and severity
time frame: Up to Day 148
AEs grade 3-4 incidence
time frame: Up to Day 148
Occurrence and titer of anti-trastuzumab antibodies
time frame: Day 1 (before the drug administration), Day 15, 64 and 127
Cmax
time frame: Up to Day 22
Tmax
time frame: Up to Day 22
T1/2
time frame: Up to Day 22
minimal serum trastuzumab concentration
time frame: Day 22, Day 43, Day 64, Day 85, Day 106, Day 127

Eligibility Criteria

Female participants from 18 years up to 75 years old.

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

Additional Information

Official title International Multicenter Randomized Double Blind Phase III Clinical Trial Comparing Safety and Efficacy of BCD-022 (CJSC BIOCAD, Russia) Used With Paclitaxel to Herceptin® (F. Hoffmann-La Roche Ltd, Switzerland) Used With Paclitaxel in the First-line Treatment of HER2-positive Metastatic Breast Cancer Patients
Trial information was received from ClinicalTrials.gov and was last updated in February 2015.
Information provided to ClinicalTrials.gov by Biocad.