A Safety and Efficacy Study of BCD-022 With Paclitaxel Compared to Herceptin With Paclitaxel in HER2+ Metastatic Breast Cancer Patients

NCT ID: NCT01764022

Last Updated: 2018-11-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 225 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2017-12-31

Brief 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.

Detailed Description

The study is based on the hypothesis of equivalence of BCD-022 (trastuzumab by JSC BIOCAD, Russia) in combination with paclitaxel used as the therapy of inoperable or metastatic HER2(+) breast cancer in comparison with Herceptin® (F. Hoffmann-La Roche Ltd., Switzerland) in combination with paclitaxel. The objectives of the study is to evaluate efficacy, safety and pharmacokinetics of BCD-022 compared with reference trastuzumab by 1. overall response rate and other efficacy parameters; 2. incidence and severity of adverse events; 3. serum concentration after the first and multiple trastuzumab administration; 4. incidence and concentration of anti-trastuzumab antibodies.

Conditions

Human Epithelial Receptor (HER)-2 Positive Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

BCD-022

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).

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: 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).

Paclitaxel

Intervention Type: DRUG

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).

Herceptin®

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).

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: 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).

Paclitaxel

Intervention Type: DRUG

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).

Interventions

Trastuzumab

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).

Intervention Type: DRUG

Paclitaxel

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).

Intervention Type: DRUG

Other Intervention Names

BCD-022; Herceptin; Taxacad

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Biocad

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roman Ivanov, MD, PhD

Role: STUDY_CHAIR

Vice-president, R&D

Locations

Brest Region Clinical Oncology Dispensary

Brest, , Belarus

Grodno Regional Hospital

Grodno, , Belarus

Gomel Region Clinical Oncology Dispensary

Homyel, , Belarus

Vitebsk State Medical University of Order of Peoples' Friendship

Vitebsk, , Belarus

HCG Bangalore Institute of Oncology

Bangalore, , India

M.S.Ramaiah Memorial Hospital

Bangalore, , India

Narayana Hrudayalaya Hospitals

Bangalore, , India

State Health Institution of Moscow "Moscow City Oncology Hospital #62 of Moscow Board of Health"

Stepanovskoye, Moscow Oblast, Russia

Arkhangelsk District Clinical Oncology Dispensary

Arkhangelsk, , Russia

Non-governmental Healthcare Institution "Railway Clinical hospital on the Chelyabinsk Station of JSC Russian Railways"

Chelyabinsk, , Russia

State-financed Health Institution "Chelyabinsk Region Clinical Oncology Dispansary"

Chelyabinsk, , Russia

State-financed Health Institution "Republican Clinical Oncology Hospital"

Izhevsk, , Russia

Institution of Russian Academy of Medical Sciences "Russian Cancer Research Center named after N.N. Blokhin"

Moscow, , Russia

Federal State Institution "Moscow Institute of Cancer Research named after P.A. Hertsen" Ministry of Health of Russian Federation

Moscow, , Russia

Regional State Health Institution "Orlov Oncology Dispansary"

Oryol, , Russia

State Health Institution "Region Oncology Dispansary"

Penza, , Russia

Perm Region Oncology Dispensary

Perm, , Russia

Federal Government Budgetary Institution "Rostov Institute of Cancer Research" of Ministry of Health of Russian Federation

Rostov-on-Don, , Russia

Military Medical Academy named after S.M. Kirov

Saint Petersburg, , Russia

Saint Petersburg City Clinical Oncology Center

Saint Petersburg, , Russia

N.N.Petrov Oncology Research Center

Saint Petersburg, , Russia

Russian scientific center of radiology and surgery technologies

Saint Petersburg, , Russia

State-financed Health Institution "Samara Region Clinical Oncology Dispansary"

Samara, , Russia

Oncology Dispensary 2

Sochi, , Russia

State-financed Health Institution "Stavropol Region Clinical Oncology Dispansary"

Stavropol, , Russia

Republican Clinical Oncology Dispensary of Ministry of Health republic Bashkortostan

Ufa, , Russia

Volgograd District Oncology Dispensary №1

Volgograd, , Russia

Donetsk City Oncology Dispensary

Donetsk, , Ukraine

Donetsk Regional Antitumor Center

Donetsk, , Ukraine

Kharkiv Regional Clinical Oncology Center

Kharkiv, , Ukraine

Kryvyi Rih Oncology Dispensary

Kryvyi Rih, , Ukraine

Lviv Regional State Cancer Diagnostics and Treatment Center

Lviv, , Ukraine

City Hospital №2

Makiivka, , Ukraine

Poltava Regional Clinical Oncology Dispensary

Poltava, , Ukraine

Zakarpatskyi Regional Clinical Oncology Center

Uzhhorod, , Ukraine

Vinnytsia Regional Clinical Oncology Dispensary

Vinnytsia, , Ukraine

Countries

Belarus; India; Russia; Ukraine

References

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.

Reference Type: DERIVED

PMID: 32819305 (View on PubMed)

Other Identifiers

BCD-022-02

Identifier Type: -

Identifier Source: org_study_id