CTRI/2014/07/004722 [Registered on: 08/07/2014] Trial Registered Retrospectively
Last Modified On:
25/10/2018
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug Biological
Study Design
Randomized, Parallel Group Trial
Public Title of Study
Phase III clinical trial comparing safety and efficacy of BCD-022 (CJSC BIOCAD, Russia) used with paclitaxel to Herceptin® used with paclitaxel in the first-line treatment of HER2 positive metastatic breast cancer patients.
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 Acronym
Secondary IDs if Any
Secondary ID
Identifier
BCD-022-02 version 2.3 dated 12 Jul 2013
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Mrutyunjaya Ganiger
Designation
Sr. Clinical Research Associate - Clinical Trials,
Affiliation
BIOCAD INDIA PVT LTD,
Address
BIOCAD INDIA PVT LTD,
163/C, 3rd Cross, 3rd Phase,
J.P.Nagar,
Bangalore KARNATAKA 560078 India
Phone
8123000277
Fax
8041699773
Email
mrutyunjaya.g@biocadindia.com
Details of Contact Person Scientific Query
Name
Dr Mrutyunjaya Ganiger
Designation
Sr. Clinical Research Associate - Clinical Trials,
Affiliation
BIOCAD INDIA PVT LTD,
Address
BIOCAD INDIA PVT LTD,
163/C, 3rd Cross, 3rd Phase,
J.P.Nagar,
Bangalore KARNATAKA 560078 India
Phone
8123000277
Fax
8041699773
Email
mrutyunjaya.g@biocadindia.com
Details of Contact Person Public Query
Name
Dr Mrutyunjaya Ganiger
Designation
Sr. Clinical Research Associate - Clinical Trials,
Affiliation
BIOCAD INDIA PVT LTD,
Address
BIOCAD INDIA PVT LTD,
163/C, 3rd Cross, 3rd Phase,
J.P.Nagar,
Acharya Harihar Regional Cancer Centre, Cuttack, Pin-753007, Odisha Cuttack ORISSA
9583388288
drprasantdm@gmail.com
Dr Surender Kumar Beniwal
Acharya Tulsi hospital, Bikaner, Rajathan
Acharya Tulsi Regional Cancer Treatment and Research Institute,S P Medical College
and AG Hospitals, Bikaner 334003, Rajasthan.
Bikaner RAJASTHAN
9414370484
beniwal.surendra@gmail.com
Dr Saroj Kumar Das Majumdar
AIIMS Bhubhaneshwar
All India Institute Medical Sciences, Bhubaneswar, Sijua, Patrapada, Bhubaneswar, Odisha, Pin- 751019 Khordha ORISSA
94389884066
sarojmajumdar@gmail.com
Dr H D Jayanti
BGS Global- Bangalore
BGS Global HosPitals, BGS
Health and Education CitY, #
67, lJttarahalli Road, Kengeri,
banglore-560060, I{arnataka,
India. Bangalore KARNATAKA
99845065762
drjayantisthumsi@gmail.com
Dr M Vikranth
City Cancer Centre
City Cancer Centre.
City cancer center, 33-25-33, Ch.Venkata
Krishnayya Street, Suryarao pet, Vijayawada
520002, Andhra Pradesh, India
Krishna ANDHRA PRADESH
9603548495
mumaneni.vikranth@gmail.com
Dr Amit Kumar Dhiman
Dayanad Medical College and hospital
Dayanad Medical College and hospital tagore nagar, Civil Lines, Ludhiana-14100 1, Punjab Ludhiana PUNJAB
9872188664
dramit.meet@gmail.com
Dr Amit Bhargava
Fortis Hospital
Fortis Hospital, B-22, Sector-
62, Noida-2O1301, Uttar
Pradesh, India Gautam Buddha Nagar UTTAR PRADESH
9811065538
amitbharga@gmail.com
Dr Sampath Kumar MN
HCG-Bangalore Institute of Oncology
HCG-Bangalore Institute of Oncology,Dpt of Oncology
8, P Kalinga Rao Road,
Near- GEO Hotel, Sampangirama Nagar , Bangalore-560027, Karnataka Bangalore KARNATAKA
8792241377 08040206059 sampathkumarmn02@gmail.com
Dr Randeep Singh
HCG-Delhi
HCG SMH Curie Cancer
Centre, 2, Institutional Area,
Vikas Marg Extension, Near
metro Pillar No. 116, Karkar
dooma, New Delhi-1 lOO92 East DELHI
9582449448
drrandeep@yahoo.co.in
Dr Rajesh Kumar Singh
Indira Gandhi Institute of Medical Science
Regional Cancer Centre, Indira Gandhi Institute of Medical Sciences, Sheikhpura, Patna -800014,Bihar Patna BIHAR
9939088899
drrajeshsingh@yahoo.com
Dr Kirti Srivatsava
King George Medical College,
KGMC, Dpt of Radiotherapy. Shah Mina Road,
Chowk, Lucknow-226003, Uttar Pradesh Lucknow UTTAR PRADESH
9335920571
drkirtis@rediffmail.com
DrKrishna Prasad
Manipal Hospital, Mangalore
Kasturba Medical College Hospital Attavar, Mangalore-575001, Karnataka Dakshina Kannada KARNATAKA
9880345666
drkrishnaprasad@hotmail.com
Dr P Ananda Selva Kumar
Meeenakshi Mission Hospital And Research Centre
Meeenakshi Mission Hospital And Research Centre Lake Area, Melur Road Madurai, 625107, Tamilnadu Madurai TAMIL NADU
9894333759
drask81@yahoo.co.in
Dr Minish Jain
Noble Hospital,
Noble Hospital, dpt of Oncology.
153, Magarpatta
City Road , Hadapsar, Pune-411013 , Maharashtra Pune MAHARASHTRA
09823133390
minishjain009@gmail.com
Dr Anjan Bera
NRS Medical College,Kolkata
N.R.S Medical College and Hospital, 138, A.J.C Bose Rd, Kolkata, West Bengal 700014 Kolkata WEST BENGAL
8336855482
anjanbera78@gmail.com
Dr Subir gangopadhyay
RG Kar Medical College and Hospita
RG tar Medical College and
Hospitai, 1, Khudiram Bose
sarani, ko1kata, west Bengal
700004 Kolkata WEST BENGAL
9830033294
drsubirganguly@gmail.com
Dr Patil Tushar Vishvasrao
Sahyadri Speciality hospital, Pune
Sahyadri Speciality Hospital 30C, Erandawane, Karve Road Pune – 411004, Maharashtra Pune MAHARASHTRA
9552522556
tussipars@hotmail.com
Dr Satish Srinivas
Sri Ramachandra Hospital,
Sri Ramachandra Hospital, dpt Of Oncology
No. I,
Ramchandra Nagar, Porur, Chennai-
600116, Tamil Nadu Chennai TAMIL NADU
9884780974
drsatishsrinvas@rediffmail.com
Dr Chiradoni Thugappa Satheesh
Sri Venkateshwara Hospital
Sri Vent ateshwara HosPital
#86, Hosur main Road
Madiwala, Banglore 560068
Karnataka, India Bangalore KARNATAKA
9242698750
svhospitalresearch@gmail.com
DrTM Suresh
Srinivassam cancer care Hospita
Srinivassam cancer care
Hospital #236 I L, VijaYashree
layout, Arekere, Bannerghatta
Main road, Banglore-560076 Bangalore KARNATAKA
9448055949
sureshtm1955@yahoo.com
Dr Yogesh Jain
Sujan Surgical cancer hospital and Amravati cancer foundation
Sujan Surgical Cancer Hospital and Amravati Cancer Foundation, 52/B, Shankar Nagar, Main Road, Amravati 446001, Maharashtra Amravati MAHARASHTRA
Patients with HER2-positive metastatic breast cancer.,
Intervention / Comparator Agent
Type
Name
Details
Intervention
BCD-022 (trastuzumab manufactured by CJSC BIOCAD, Russia)
In the study after signing the informed consent and completing screening procedures, patients will be stratified and randomly assigned (randomized) to receive BCD-022 and paclitaxel in 1:1 ratio.
Patients will be stratified according to previous treatment (anthracyclines used/not used, taxanes and/or other anti-HER2 medications used/not used), estrogen and/or progesterone receptor status (ER and/or PR expressed/not expressed) and age (55/≥55 years).
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).
Comparator Agent
Herceptin® (F. Hoffmann-La Roche Ltd., Switzerland).
In the study after signing the informed consent and completing screening procedures, patients will be stratified and randomly assigned (randomized) to receive Herceptin® and paclitaxel in 1:1 ratio.
Patients will be stratified according to previous treatment (anthracyclines used/not used, taxanes and/or other anti-HER2 medications used/not used), estrogen and/or progesterone receptor status (ER and/or PR expressed/not expressed) and age (55/≥55 years).
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).
1. Written informed consent and ability to follow the Protocol procedures;
2. Age18 years and age 75 years;
3. Female gender;
4. Histologically confirmed breast cancer (BC);
5. Metastatic BC (stage IV according to TNM classification version 6);
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) ;
7. Documented results of oestrogen and progesterone receptors expression analysis;
8. ECOG status 0, 1 or 2, not increasing within 2 weeks prior to randomization;
9. Life expectancy – 20 weeks or more from the moment of randomization;
10. Presence of at least 1 tumour lesion with a size not less than 1 cm (revealed with CT slice thickness not more than 5 mm). Patients having bone metastasis as the only measurable tumour lesion are not eligible for the trial;
11. 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 .
ExclusionCriteria
Details
1. 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;
2. Disease progression within 6 months after adjuvant and/or neoadjuvant BC therapy.
3. Surgery, radiation therapy, hormonal therapy, use of any experimental medications within 4 weeks (28 days) prior to randomization.
4. 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;
5. BC metastases in CNS, 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;
6. Cardiovascular system pathology (CHF stage III-IV according to NYHA classification, unstable angina pectoris, myocardial infarction) within 12 months prior to randomization;
7. 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);
8. Left ventricular ejection fraction <50% according to ECG;
9. Neutrophils ≤1500/mm3;
10. Platelets ≤100 000/mm3;
11. Hemoglobin ≤90 g/L;
12. Creatinine level ≥ 1.5 × upper limit of normal (ULN);
13. Bilirubin level ≥ 1.5 × ULN;
14. AST and ALT levels ≥ 2.5 × ULN (5 × ULN for patients with liver metastases);
15. Alkaline phosphatase level ≥ 5 × ULN;
16. Pregnancy or lactation;
17. 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;
18. Conditions limiting patient’s adherence to protocol requirements (dementia, neurologic or psychiatric disorders, drug addiction, alcoholism and others);
19. Stage II-IV neuropathy according to CTCAE v.4.0;
20. 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;
21. Acute or active chronic infections;
22. HCV, HBV, HIV or syphilis infections;
23. Obstacles in intravenous administration of study drugs.
The therapy efficacy will be evaluated using contrast-enhanced computed tomography (CT) data. The efficacy analysis will include all randomized evaluable patients (ITT – intent-to-treat analysis). Contrast-enhanced CT will be performed at screening, after 3 therapy cycles (21±3 days after 3rd administration of investigational product) and after 6 therapy cycles (21±3 days after 6th administration of investigational product).
•Saftey and efficacy evaluation.
•AE incidence in both groups.
•Treatment discontinuation due to adverse events.
•Pharmacokinetics evaluation.
To evaluate overall response rate
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
It is 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.The main objective of the study
is to evaluate overall response rate and other efficacy parameters,
Incident and severity of adverse events, determination of Serum concentration
of trastuzumab after the first administration and incidence and concentration of anti-trastuzumab
antibodies in patients with HER2(+) mBC treated with BCD-022 or Herceptin® administered in combination with paclitaxel. 40 patients
with HER2-positive
metastatic breast cancer will be recrited into the study. After signing the
informed consent and completing screening procedures, patients will be
stratified and randomly assigned (randomized) to receive BCD-022 and paclitaxel or Herceptin® and
paclitaxel in 1:1 ratio.The study will be conducted at 18 sites of India.
Trastuzumab is a humanized monoclonal
antibody (mAb), specific to HER2 extracellular domain. Number of randomized
clinical studies showed that trastuzumab in combination with or followed by adjuvant
chemotherapy significantly increases treatment efficacy in patients with early
stage BC. Trastuzumab in patients with HER2+ BC reduces relapse rate by
approximately 2 folds and mortality – by one third. According to these data, trastuzumab was approved as therapy
standard for early stages HER2+ BC. Trastuzumab addition to the therapy of
metastatic BC and metastatic GC also increases therapy efficacy.CJSC BIOCAD has
developed a trastuzumab which is a full equivalent (biosimilar) of Herceptin®.
The full cycle of biosimilar trastuzumab production is localized in Russia.
Preclinical studies of trastuzumab manufactured by CJSC BIOCAD show that its
pharmacokinetics and toxicity are equivalent to those of Herceptin®.
Studies conducted on primates showed no significant differences in CJSC BIOCAD
trastuzumab and Herceptin® safety parameters. Multicenter double-blind randomized clinical
study of BCD-022 (CJSC BIOCAD, Russia) and Herceptin® (F.Hoffmann-La
Roche., Switzerland) showed that safety and pharmacokinetic profiles of these
drugs were equivalent when used in combination with paclitaxel in mBC HER2+
patients. Consequently, BCD-022 can be recommended for further clinical study
of safety and efficacy in this population.