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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Biocad
Sponsor:
Information provided by (Responsible Party):
Biocad
ClinicalTrials.gov Identifier:
NCT01764022
First received: January 7, 2013
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
HER2-positive Metastatic Breast Cancer
Drug: Trastuzumab
Drug: Paclitaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Biocad:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: Day 127 ] [ Designated as safety issue: No ]
    primary outcome measure for efficacy evaluation

  • 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) ] [ Designated as safety issue: No ]
    primary outcome measure for pharmacokinetics (PK) substudy


Secondary Outcome Measures:
  • Complete response rate [ Time Frame: Day 127 ] [ Designated as safety issue: No ]
    secondary outcome measure for efficacy evaluation

  • Partial response rate [ Time Frame: Day 127 ] [ Designated as safety issue: No ]
    secondary outcome measure for efficacy evaluation

  • Stabilization rate [ Time Frame: Day 127 ] [ Designated as safety issue: No ]
    secondary outcome measure for efficacy evaluation

  • Progression rate [ Time Frame: Day 127 ] [ Designated as safety issue: No ]
    secondary outcome measure for efficacy evaluation

  • Relative number (%) of chemotherapy cycles, postponed due to adverse events (AE) [ Time Frame: Day 127 ] [ Designated as safety issue: Yes ]
    secondary outcome measure for safety evaluation

  • Treatment discontinuation rate due to AE [ Time Frame: Day 127 ] [ Designated as safety issue: Yes ]
    secondary outcome measure for safety evaluation

  • AE incidence and severity [ Time Frame: Up to Day 148 ] [ Designated as safety issue: Yes ]
    secondary outcome measure for safety evaluation

  • AEs grade 3-4 incidence [ Time Frame: Up to Day 148 ] [ Designated as safety issue: Yes ]
    secondary outcome measure for safety evaluation

  • Occurrence and titer of anti-trastuzumab antibodies [ Time Frame: Day 1 (before the drug administration), Day 15, 64 and 127 ] [ Designated as safety issue: Yes ]
    Secondary outcome measure for immunogenicity assessment

  • Cmax [ Time Frame: Up to Day 22 ] [ Designated as safety issue: No ]
    secondary outcome measure for PK substudy

  • Tmax [ Time Frame: Up to Day 22 ] [ Designated as safety issue: No ]
    secondary outcome measure for PK substudy

  • T1/2 [ Time Frame: Up to Day 22 ] [ Designated as safety issue: No ]
    secondary outcome measure for PK substudy

  • minimal serum trastuzumab concentration [ Time Frame: Day 22, Day 43, Day 64, Day 85, Day 106, Day 127 ] [ Designated as safety issue: No ]
    Secondary outcome measure for pharmacokinetics analysis


Estimated Enrollment: 206
Study Start Date: October 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BCD-022 (CISC 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).
Drug: 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).
Other Names:
  • BCD-022
  • Herceptin
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).
Other Name: Taxacad
Active Comparator: 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).
Drug: 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).
Other Names:
  • BCD-022
  • Herceptin
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).
Other Name: Taxacad

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent and ability to follow the Protocol procedures;
  • Age from 18 years to 70 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 14 weeks 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 and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01764022

Contacts
Contact: Andrey Biryulin, MD +7 (812) 380-49-33 ext 925 biryulin@biocad.ru
Contact: Olga Filon, MD +7 (812) 380-49-33 ext 916 filonov@biocad.ru

Locations
Belarus
Brest Region Clinical Oncology Dispensary Not yet recruiting
Brest, Belarus
Gomel Region Clinical Oncology Dispensary Not yet recruiting
Gomel, Belarus
Grodno Regional Hospital Not yet recruiting
Grodno, Belarus
Vitebsk State Medical University of Order of Peoples' Friendship Not yet recruiting
Vitebsk, Belarus
India
HCG Bangalore Institute of Oncology Not yet recruiting
Bangalore, India, 560027
Narayana Hrudayalaya Hospitals Not yet recruiting
Bangalore, India, 560099
M.S.Ramaiah Memorial Hospital Not yet recruiting
Bangalore, India, 560054
Russian Federation
State Health Institution of Moscow "Moscow City Oncology Hospital #62 of Moscow Board of Health" Recruiting
Stepanovskoye, Moscow Region, Russian Federation, 143423
Arkhangelsk District Clinical Oncology Dispensary Recruiting
Arkhangelsk, Russian Federation, 163045
Non-governmental Healthcare Institution "Railway Clinical hospital on the Chelyabinsk Station of JSC Russian Railways" Recruiting
Chelyabinsk, Russian Federation, 355047
State-financed Health Institution "Chelyabinsk Region Clinical Oncology Dispansary" Recruiting
Chelyabinsk, Russian Federation, 454087
State-financed Health Institution "Republican Clinical Oncology Hospital" Recruiting
Izhevsk, Russian Federation, 426009
Federal State Institution "Moscow Institute of Cancer Research named after P.A. Hertsen" Ministry of Health of Russian Federation Recruiting
Moscow, Russian Federation, 125284
Institution of Russian Academy of Medical Sciences "Russian Cancer Research Center named after N.N. Blokhin" Recruiting
Moscow, Russian Federation, 115478
Regional State Health Institution "Orlov Oncology Dispansary" Recruiting
Orel, Russian Federation, 302020
State Health Institution "Region Oncology Dispansary" Recruiting
Penza, Russian Federation, 440071
Perm Region Oncology Dispensary Recruiting
Perm, Russian Federation, 614066
Federal Government Budgetary Institution "Rostov Institute of Cancer Research" of Ministry of Health of Russian Federation Recruiting
Rostov-on-Don, Russian Federation, 314019
Saint Petersburg City Clinical Oncology Center Recruiting
Saint Petersburg, Russian Federation, 197022
State-financed Health Institution "Samara Region Clinical Oncology Dispansary" Recruiting
Samara, Russian Federation, 443031
Oncology Dispensary 2 Recruiting
Sochi, Russian Federation, 354057
N.N.Petrov Oncology Research Center Recruiting
St.Petersburg, Russian Federation, 197758
Military Medical Academy named after S.M. Kirov Recruiting
St.Petersburg, Russian Federation, 194044
Russian scientific center of radiology and surgery technologies Recruiting
St.Petersburg, Russian Federation
State-financed Health Institution "Stavropol Region Clinical Oncology Dispansary" Recruiting
Stavropol, Russian Federation, 355047
Republican Clinical Oncology Dispensary of Ministry of Health republic Bashkortostan Recruiting
Ufa, Russian Federation, 450054
Volgograd District Oncology Dispensary №1 Recruiting
Volgograd, Russian Federation, 400138
Ukraine
Donetsk City Oncology Dispensary Not yet recruiting
Donetsk, Ukraine
Donetsk Regional Antitumor Center Not yet recruiting
Donetsk, Ukraine
Kharkiv Regional Clinical Oncology Center Not yet recruiting
Kharkiv, Ukraine
Kryvyi Rih Oncology Dispensary Not yet recruiting
Kryvyi Rih, Ukraine
Lviv Regional State Cancer Diagnostics and Treatment Center Not yet recruiting
Lviv, Ukraine
City Hospital №2 Not yet recruiting
Makiivka, Ukraine
Poltava Regional Clinical Oncology Dispensary Not yet recruiting
Poltava, Ukraine
Zakarpatskyi Regional Clinical Oncology Center Not yet recruiting
Uzhhorod, Ukraine
Vinnytsia Regional Clinical Oncology Dispensary Not yet recruiting
Vinnytsia, Ukraine
Sponsors and Collaborators
Biocad
  More Information

Additional Information:
No publications provided

Responsible Party: Biocad
ClinicalTrials.gov Identifier: NCT01764022     History of Changes
Other Study ID Numbers: BCD-022-02
Study First Received: January 7, 2013
Last Updated: January 10, 2014
Health Authority: Russia: Ministry of Health of the Russian Federation

Keywords provided by Biocad:
breast cancer
trastuzumab

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Trastuzumab
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014