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

NCT01764022 | Completed Phase 3 Results

• 1 other identifier: BCD-022-02
• Study Type: interventional
• Target: 225
• Locations: 4 countries
• Sites: 36

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.

Conditions

Human Epithelial Receptor (HER)-2 Positive Breast Cancer

Keywords

breast cancer; trastuzumab

Outcome Measures

Primary Outcomes (2)

• 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 (12)

• Complete Response Rate

  Day 127

• Partial Response Rate

  Day 127

• Stabilization Rate

  Day 127

• Progression Rate

  Day 127

• Treatment Postponed Due to AE/SAE

  Day 127

Study Arms (2)

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

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).

Also known as: BCD-022, Herceptin

BCD-022; Herceptin®

Paclitaxel 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).

Also known as: Taxacad

BCD-022; Herceptin®

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Biocad: lead

Study Sites (36)

Brest Region Clinical Oncology Dispensary

Brest, Belarus

Location

Grodno Regional Hospital

Grodno, Belarus

Location

Gomel Region Clinical Oncology Dispensary

Homyel, Belarus

Location

Vitebsk State Medical University of Order of Peoples' Friendship

Vitebsk, Belarus

Location

HCG Bangalore Institute of Oncology

Bangalore, 560027, India

Location

M.S.Ramaiah Memorial Hospital

Bangalore, 560054, India

Location

Narayana Hrudayalaya Hospitals

Bangalore, 560099, India

Location

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

Stepanovskoye, Moscow Oblast, 143423, Russia

Location

Arkhangelsk District Clinical Oncology Dispensary

Arkhangelsk, 163045, Russia

Location

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

Chelyabinsk, 355047, Russia

Location

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

Chelyabinsk, 454087, Russia

Location

State-financed Health Institution "Republican Clinical Oncology Hospital"

Izhevsk, 426009, Russia

Location

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

Moscow, 115478, Russia

Location

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

Moscow, 125284, Russia

Location

Regional State Health Institution "Orlov Oncology Dispansary"

Oryol, 302020, Russia

Location

State Health Institution "Region Oncology Dispansary"

Penza, 440071, Russia

Location

Perm Region Oncology Dispensary

Perm, 614066, Russia

Location

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

Rostov-on-Don, 314019, Russia

Location

Military Medical Academy named after S.M. Kirov

Saint Petersburg, 194044, Russia

Location

Saint Petersburg City Clinical Oncology Center

Saint Petersburg, 197022, Russia

Location

N.N.Petrov Oncology Research Center

Saint Petersburg, 197758, Russia

Location

Russian scientific center of radiology and surgery technologies

Saint Petersburg, Russia

Location

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

Samara, 443031, Russia

Location

Oncology Dispensary 2

Sochi, 354057, Russia

Location

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

Stavropol, 355047, Russia

Location

Republican Clinical Oncology Dispensary of Ministry of Health republic Bashkortostan

Ufa, 450054, Russia

Location

Volgograd District Oncology Dispensary №1

Volgograd, 400138, Russia

Location

Donetsk City Oncology Dispensary

Donetsk, Ukraine

Location

Donetsk Regional Antitumor Center

Donetsk, Ukraine

Location

Kharkiv Regional Clinical Oncology Center

Kharkiv, Ukraine

Location

Kryvyi Rih Oncology Dispensary

Kryvyi Rih, Ukraine

Location

Lviv Regional State Cancer Diagnostics and Treatment Center

Lviv, Ukraine

Location

City Hospital №2

Makiivka, Ukraine

Location

Poltava Regional Clinical Oncology Dispensary

Poltava, Ukraine

Location

Zakarpatskyi Regional Clinical Oncology Center

Uzhhorod, Ukraine

Location

Vinnytsia Regional Clinical Oncology Dispensary

Vinnytsia, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 32819305 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Dr. Mariia Shustova
• Organization: BIOCAD

shustova@biocad.ru

+7812380 49 33

Study Officials

• Roman Ivanov, MD, PhD

  Vice-president, R&D

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2013
• First Posted: January 9, 2013
• Study Start: October 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: December 1, 2017
• Last Updated: November 29, 2018
• Results First Posted: October 24, 2016

Record last verified: 2018-11

Locations

BE (4); IN (3); RU (20); UA (9)