CTRI/2018/09/015794 [Registered on: 20/09/2018] Trial Registered Prospectively
Last Modified On:
22/02/2021
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
This is a clinical trial to compare the safety and effectiveness of Eirgenix trastuzumab with Herceptin as Neoadjuvant treatment in HER2 positive Early Stage Breast Cancer
Scientific Title of Study
Phase III, Randomized, Multicenter, Double-blind study to compare efficacy and safety of EG12014 (Eirgenix Trastuzumab) with Herceptin® as Neoadjuvant treatment in combination with Anthracycline/Paclitaxel-based systemic therapy in patients with HER2-positive Early breast cancer
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
NCT03433313
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Radhika Bobba
Designation
Regional Director
Affiliation
PSI CRO pharma India Pvt Ltd
Address
PSI CRO Pharma India Pvt Ltd|414 Shree complex, 73, St Johns Road| Bangalore|India
Bangalore KARNATAKA 560042 India
Phone
Fax
Email
Kruthika.Nagaraj@psi-cro.com
Details of Contact Person Scientific Query
Name
Radhika Bobba
Designation
Regional Director
Affiliation
PSI CRO pharma India Pvt Ltd
Address
PSI CRO Pharma India Pvt Ltd|414 Shree complex, 73, St Johns Road| Bangalore|India
KARNATAKA 560042 India
Phone
Fax
Email
Kruthika.Nagaraj@psi-cro.com
Details of Contact Person Public Query
Name
Radhika Bobba
Designation
Regional Director
Affiliation
PSI CRO pharma India Pvt Ltd
Address
PSI CRO Pharma India Pvt Ltd|414 Shree complex, 73, St Johns Road| Bangalore|India
KARNATAKA 560042 India
Phone
Fax
Email
Kruthika.Nagaraj@psi-cro.com
Source of Monetary or Material Support
Eirgenix, Inc,
101, Lane 169, Kangning Street
Xizhi Dist
New Taipei City 22180
Taiwan, R.O.C.
Primary Sponsor
Name
Eirgenix Inc
Address
101, lane 169, Kangning Street, Xizhi Dist, New Taipei city 22180, Taiwan, R.O.C
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
PSI CRO Pharma India Pvt Ltd
414, Shree Complex, 73, St. Johns road, Bangalore, Karnataka, India
Countries of Recruitment
Belarus Chile Colombia Democratic People's Republic of Korea Georgia India Lithuania Republic of Korea Republic of Moldova Russian Federation South Africa Taiwan Ukraine United States of America
Sites of Study
No of Sites = 9
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
DrArun Warrier
Aster medicity
Centre of Excellence, Medical Oncology, Kuttisahib Road, Near Kothad Bridge, South Chittoor, Cheranalloor, Kochi, Kerala 682027 Ernakulam KERALA
7594000556
keerthy.j@asterhospital.com
DrAshish Singh
CMC Vellore
Department of Medical Oncology, CMC College and Hospital Ida Scudder Road, Vellore, Tamil Nadu 632004 Vellore TAMIL NADU
9894741481
prabakarbioinfo@gmail.com
DrPrasad Narayanan
Cytecare Cancer Hospital,
Department of Medical Oncology, Venkatala, Near Bagalur Cross, Bellary Rd, Yelahanka, Bengaluru, Karnataka 560064 Bangalore KARNATAKA
9895822926
asha.nair@cytespace.com
DrGovindbabu
HCG Koramangala
Department of Medical Oncology, No.88, 2nd cross, 17th A main, 5th block, Koramangala Bangalore KARNATAKA
08025538194
kgblaugh@gmail.com
DrAjay Mehta
HCG NCHRI Cancer Center
Department of Clinical Research, 5th floor, Khasra, No.50,51, Mauja Wanjari Bande, Nawa Nagar, Near Automotive Square, Kalmana Ring road, Nagpur, 440026 Nagpur MAHARASHTRA
9860092030
nilesh.dongre@strandls.com
DrRaghunadharao
Homi Bhabha Cancer Hospital and Research Centre
Department of Medical Oncology, APPIIC, Industrial Park, NH%, Aganampudi, Visakhapatnam - 530053 Visakhapatnam ANDHRA PRADESH
08912871555
telerama@rediffmail.com
DrAnand Misra
King George Medical University
Department of Endocrine surgery, Shatabdi Phase-II, King George Medical University, Shahmina Road, Chowk, Lucknow, Uttar Pradesh Lucknow UTTAR PRADESH
9454202194
rajeevmsr01@gmail.com
DrMinish Jain
Noble Hospital
Clinical research department, basement, Noble Hospital 153, Magarpatta City Road, Hadapsar, Pune, Maharashtra 411013 Pune MAHARASHTRA
9890011621
shri.xylemcr@gmail.com
DrSudeep Gupta
Tata Memorial Hospital
Department of Medical Oncology, R.No.119,11th,Floor,Homi Bhabha, Block,Dr.Ernest Borges Marg,Parel,Mumbai-400012 Mumbai MAHARASHTRA
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Eirgenix Trastuzumab - EG12014
EG12014 is a proposed biosimilar product of Herceptin developed by EirGenix, Inc.
EG12014 is a mammalian cell culture-derived humanized monoclonal antibody directed
against the extracellular domain of HER2 on human cancer cells.
Dose: 8mg/kg loading dose followed by 6mg/kg by continuous IV infusion followed by paclitaxel only in neoadjuvant treatment
Frequency:4 treatment cycles 3 weeks each as neoadjuvant
13 cycles 3 weeks each as adjuvant post surgery
Total duration of the therapy: 12 weeks in neoadjuvant and 40 weeks in adjuvant treatment.
Comparator Agent
Traastuzumab
Trastuzumab (Herceptin®, Roche/Genentech) is a humanized monoclonal antibody
directed against the extracellular domain of HER2.
Dose: 8mg/kg loading dose followed by 6mg/kg by continuous IV infusion Frequency:4 treatment cycles 3 weeks each followed by paclitaxel as neoadjuvant treatment.
13 cycles 3 weeks each as adjuvant post surgery.
Total duration of the therapy: 12 weeks in neoadjuvant and 40 weeks in adjuvant treatment.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Female
Details
Patients will be entered into this study only if they meet all of the following criteria:
1. Provide signed and dated written informed consent before entering the study. The
informed consent will cover both parts of the study (neoadjuvant part and adjuvant
part).
2. Female, ≥18 and ≤65 years of age.
3. Histologically-confirmed invasive carcinoma of the breast (American Joint
Committee on Cancer [AJCC] Stage II, IIIa [43]).
4. Operable breast cancer, planned surgical resection of breast tumor (mastectomy or
lumpectomy) and sentinel or axillary lymph nodes.
5. Ipsilateral, measurable tumor of the breast ≥2 cm in diameter.
6. HER2-positive tumor, defined as 3+ score by IHC or fluorescence positive by FISH.
7. Known estrogen receptor (ER) and progesterone receptor (PrR) status at study entry.
8. Adequate bone marrow function, defined as granulocyte count of ≥1.500/μL, and
platelet count of ≥100.000/μL.
9. Adequate hepatic and renal function, defined as:
bilirubin within normal range
alanine aminotransferase (ALT) ≤2 x upper limit of normal (ULN)
aspartate aminotransferase (AST) ≤2 x ULN
gamma glutamyl transferase (GGT) ≤3 x ULN
serum creatinine <1.5 mg/dL
10. International normalized ratio ≤1.5×ULN (2 to 3×ULN if on anticoagulants) or
prothrombin time ≤1.5×ULN; activated partial thromboplastin time ≤1.5×ULN.
11. Hemoglobin concentrations within the normal ranges.
12. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
13. LVEF ≥55%, measured by multiple-gated acquisition (MUGA) scan or
echocardiography.
14. Negative pregnancy test at entry, women of childbearing potential have to use
contraceptives during the course of the study.
Females with childbearing potential must provide a negative serum pregnancy test at
Screening and must be using adequate birth control. Adequate birth control is defined
as agreement to consistently practice an effective and accepted method of
contraception throughout the duration of the study and for 6 months after study drug
treatment. These methods include hormonal contraceptives, intrauterine device, or
double barrier contraception (i.e., condom + diaphragm) or a male partner with
documented vasectomy.
Non-childbearing potential is defined as post-menopausal for at least 1 year or
surgical sterilization or hysterectomy at least 3 months before study start.
4.2 Inclusion Criterion after Surgery (Adjuvant Part of the Study)
After completion of the neoadjuvant part of the study and surgery, patients will be
eligible for double-blind adjuvant therapy with EG12014 or Herceptin if they meet the
following criterion:
1. No sequelae have occurred after neoadjuvant therapy, in particular regarding cardiac
function. No separate informed consent is required.
ExclusionCriteria
Details
Patients will be entered into this study only if they meet none of the following criteria:
1. Bilateral breast cancer.
2. Pregnancy or lactation or considering becoming pregnant.
3. Metastases, other than sentinel/axillary lymph nodes.
4. Previous treatment (chemotherapy, biologic therapy, radiation, or surgery) for
invasive malignant disease or other concomitant active malignancy, other than
basal-cell carcinoma of the skin. Previous treatment for carcinoma in situ of the
cervix is allowed.
5. Other serious illness or medical disorder.
6. Previous treatment with Herceptin.
7. Angina pectoris or arrhythmia requiring medication; poorly controlled hypertension;
left ventricular hypertrophy on echocardiography; history of myocardial infarction or
cardiac failure, New York Heart Association (NYHA) class II or higher; clinically
significant cardiac valvular disease; hemodynamic effective pericardial effusion;
other cardiomyopathies; coronary artery disease; LVEF of <55%.
8. Any investigational treatment less than 30 days prior to study entry, or within a time
interval less than at least 5 half-lives of the investigational medicinal product,
whichever is longer.
9. Positive diagnostic test for hepatitis B virus (HBV), hepatitis C virus (HCV), or
human immunodeficiency virus (HIV).
10. History of hypersensitivity to the study drug or to drugs with similar chemical
structures.
11. History of, or known current problems with, drug or alcohol abuse.
12. Other serious illness, medical disorder or condition that, in the opinion of the
Investigator, would make the patient unsuitable for participation in the study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
The primary objective of this study is to demonstrate therapeutic
equivalence of EG12014 and Herceptin, both given in combination
with paclitaxel for 12 weeks (4 cycles) as part of neoadjuvant
therapy in patients with human epidermal growth factor receptor 2
(HER2)-positive early breast cancer (EBC), in terms of efficacy
determined by pathological complete response (pCR) (ypT0/is ypN0)
at the time of surgery, assessed by central laboratory.
Tumor response will be evaluated after completion of the neoadjuvant treatment and prior to surgery by clinical examination, mammography, and /or ultrasound and CT/MRI. Resected specimens of breast tissue and axillary lymph nodes will be evaluated for
pathological response by a central laboratory, and used for the assessment of the primary
endpoint.
Secondary Outcome
Outcome
TimePoints
Further evaluation of pCR at surgery (ypT0 ypN0, and ypT0/is)
pCR at the time of surgery, where pCR is defined as the absence of residual invasive cancer and of DCIS (ypT0 ypN0) from breast tissue and sentinel/axillary lymph nodes, as assessed by central laboratory pCR at the time of surgery, defined as the absence of invasive cancer in breast tissue only (ypT0/is), as assessed by central laboratory
Evaluation of EFS
EFS up to end of study (EOS), defined as time from initial randomization to the date when disease recurrence or progression (local, regional, distant or contralateral) is diagnosed according to institutional standard, or date of death of any cause, whichever is earlier
Evaluation of overall response (OR) prior to surgery according to RECIST v1.1 criteria
OR: Objective response prior to surgery, defined as PR or CR according to RECIST v1.1 on Screening and at pre surgery
Evaluation of OS
OS: up to End of study, defined as time from the date of initial randomization to the date of death
Comparison of the safety profile of EG12014 and Herceptin during neoadjuvant treatment, and the safety of EG12014 and Herceptin during the entire study
Incidence of AEs (including severity, seriousness, and relationship to study drug) and laboratory abnormalities
Cardiac safety – ECG/ECHO or MUGA at Screening Cycle 5 (neoadjuvant), Pre-surgery, post-surgery(ECG), Cycle1,5,9 and 13 (adjuvant), End of treatment and End of study
Evaluation of the immunogenicity of EG12014 and Herceptin
Immunogenicity: Incidence and titer of ADA. Day 1 of Cycle 1 and 5 (neoadjuvant), Pre-surgery, Day 1 of cycles 1, 5, 9, 13 (adjuvant), and EOT
Comparison of EG12014 and Herceptin pharmacokinetics (PK) in the neoadjuvant setting
Serum trastuzumab concentration and/or population PK: Day 1 of Cycle 1, 5, 6, 7 and 8 (neoadjuvant), Pre-surgery (at 3 weeks after the last dose of neoadjuvant chemotherapy), Day 1 of cycles 1, 5, 9, 13 (adjuvant) and End of treatment
Target Sample Size
Total Sample Size="800" Sample Size from India="77" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This international, Phase III, randomized, double-blind clinical study is to prove equivalence, regarding safety and efficacy (the EMA position), and to demonstrate that there are no clinically meaningful differences in terms of response, safety, purity, and potency (the FDA position) between EG12014 and EU licensed Herceptin. Thereby, the FDA could accept the EGC002 study findings in exactly the same way for US-licensed Herceptin.
In this study, the proposed biosimilar (EG12014), and EU-licensed Herceptin will be studied in patients with EBC (i.e., with operable disease, stage T3N1M0), who constitute a sensitive and homogeneous population. Patients with locally advanced breast cancer (LABC) with stage T3N2-3M0 or greater will be excluded. pCR will be evaluated in the neoadjuvant setting, in order to provide a robust basis for regulatory approval of EG12014 as a proposed biosimilar product to Herceptin.