CTRI/2019/01/017029 [Registered on: 10/01/2019] Trial Registered Prospectively
Last Modified On:
19/07/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A clinical study to compare the efficacy, safety and immunogencity of two formulations of trastuzumab in women with HER2 Positive Early breast cancer.
Scientific Title of Study
A randomized, double-blind, parallel group, Phase III trial to compare the efficacy, safety, and immunogenicity of TX05 with Herceptin® in subjects with HER2 positive early breast cancer
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
TX05-03 Amendment 1 Protocol Version Final dated 30/Nov/17
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Belarus Brazil Bulgaria Chile Georgia Hungary Italy Mexico Peru Republic of Korea Russian Federation Slovakia Thailand Ukraine India Poland Romania Philippines
Deenanath Mangeshkar Hospital& Research Center ,Erandawane, Pune -411004, Maharashtra, India Pune MAHARASHTRA
0091-9324517648
sshingmire@yahoo.com
Dr Neeti Sharma
Acharya Tulsi Cancer Regional Cancer Treatment & Research Institute
Acharya Tulsi Cancer Regional Cancer Treatment & Research Institute, S P Medical College & AG of Hospitals, Bikaner 334003, Rajasthan, India. Bikaner RAJASTHAN
01512226329
drneetisharma@gmail.com
Dr Raja Madras Ananthanarayanan
Apollo Speciality Hospital
Apollo Hospitals Enterprises Limited, 21, Greams Lane,Off Greams Road,Chennai-600006, Tamil Nadu India Chennai TAMIL NADU
0091-9840531350
drmaraja@gmail.com
Dr Hari Krishnan Goyal
Artemis Hospitals - Artemis Cancer Centre
Sector-51, Gurgaon-122001, Haryana, India Gurgaon HARYANA
0919958715678
harig@artemishospitals.com
Dr Senthil Jagannathan Rajappa
Basavatarakam Indo American Cancer Hospital & Research Institute
Road No 10, Banjara Hills, Hyderabad,Telangana 500034 Hyderabad TELANGANA
4023550015
senthiljrajappa@gmail.com
Dr Naresh Somani
Bhagwan Mahaveer Cancer Hospital & Research Centre
Bhagwan Mahaveer Cancer Hospital & Research Centre ,Jawahar Lal Nehru Marg, Jaipur -302017, Rajasthan, India Jaipur RAJASTHAN
0091-9829014996
bmchrcclinicaltrial@gmail.com
Dr Nagesh Shrinivasrao Madnoorkar
Chopda Medicare & Research Center Pvt Ltd, Magnum Heart Institute
Consulting room 3, Ground floor,3/5, Patil Lane No. 1, Laxmi Nagar, Near K.B.H. Vidyalaya, Canada corner, Nashik-422005, Maharashtra, India Nashik MAHARASHTRA
481, Model Town Ludhiana-141002 Punjab India Ludhiana PUNJAB
911614628234
dramit.meet@gmail.com
Dr Krishna Sharan
Department of Radiotherapy and Oncology,Shirdi Sai Baba Cancer Hospital & Research Centre
Shirdi Sai Baba Cancer Hospital & Research Centre (A Unit of Kasturba Hospital), Madhav Nagar, Manipal – 576104, Karnataka, India Udupi KARNATAKA Udupi KARNATAKA
0091-8255238216
tk.sharan@gmail.com
Dr Arun Seshachalam
Dr. GVN Cancer Institute (a Unit of G.V.N Hospital)
No. 46, Singarathope, Trichy-620008, Tamil Nadu, India. Tiruchirappalli TAMIL NADU
4312705979
arunonco@gmail.com
Dr Arumugham Rajkumar
G. Kuppuswamy Naidu Memorial Hospital
G. Kuppuswamy Naidu Memorial Hospital,
Post box No. 6327 Nethaji Road, Pn. Palayam, appanaickenpalaya, Coimbatore, TamilNadu, Pin-641 037 Coimbatore TAMIL NADU
HCG- Bangalore Institute on Oncology, HCG Towers, Tower 1, 1St Floor, # 8, P. Kalinga Rao Road, Sampangi Ram Nagar, Bangalore- 560027, Karnataka, India Bangalore KARNATAKA
0091-9242698750
drsatheeshct@gmail.com
Dr Kartikeya Jain
Himalaya Hospital & Research Institute
Third floor, Dept. of Medical Oncology #4 Vinod Baugh, Jetalpur bridge, Alkapuri - 390007 Vadodara GUJARAT Vadodara GUJARAT
0091-9427432642
divahogclinic@gmail.com
Dr Rajendra Kumar
King George’s Medical University
King George’s Medical University, Department of Radiotherapy, Lucknow- 226003, Uttar Pradesh, India Lucknow UTTAR PRADESH
0091-9369918180
drrkumar10@gmail.com
Dr Mahesh Kalloli
KLE Dr. Prabhakar Kore Hospital & Medical Research Center
Nehru Nagar, Belgaum-590010, Karnataka, India Belgaum KARNATAKA
9945014996
mahesh.kalloli@gmail.com
Dr Ravikumar Narayan Wategaonkar
Life Point Mutispecialty Hospital
145/1, Mumbai – Bangalore Highway, Near Hotel Sayaji, Bhumkar Chowk, Wakad,Pune-411057 Pune MAHARASHTRA
02066434343
rnwategaonkar@gmail.com
Dr Chanchal Goswami
Medica Superspecialty Hospital
6th Floor, Clinical Research Department, MEDICA Superspecialty Hospital, 127, Mukundapur, E.M. Bypass, Kolkata- 700099, West Bengal, India Kolkata WEST BENGAL
0091-9830055035
drcgoswami@gmail.com
Dr Krishna Kumar Rathnam
Meenakshi Mission Hospital and Research Centre
Meenakshi Mission Hospital and Research Centre, Lake Area , Melur Road, Madurai-625 107 , Tamilnadu , India Madurai TAMIL NADU
0091-9380417299
kkrathnam@gmail.com
Dr Srinivasulu Mukta
MNJ Institute of Oncology and Regional Cancer Centre
3rd Floor, Room No. 11, Red Hills Hyderabad-500004, Telangana, India. Hyderabad TELANGANA
9849044816
muktasrinivasulu@yahoo.co.in
Dr Bodhisatta Roy
Netaji Subhas Chandra Bose Cancer Hospital
Netaji Subhas Chandra Bose Cancer Hospital,3081, Nayabad, New Garia, Kolkata-700094 India. Kolkata WEST BENGAL
9330766762
bodhisatta.roy26@gmail.com
Dr Anjan Bera
Nil Ratan Sircar Medical College & Hospital
Nil Ratan Sircar Medical College & Hospital,138, Acharya Jagadish Chandra Bose Road, Sealdah, Kolkata, West Bengal 700014, India Kolkata WEST BENGAL
8336855482
anjanbera@gmail.com
Dr Sandeep Kumar Jasuja
R.K. Birla Cancer Centre
R.K. Birla Cancer Centre Department of Medical Oncology and BMT,SMS Medical College and Attached Hospitals JLN Marg, Jaipur-302004, Rajasthan , India Jaipur RAJASTHAN
0091-9660121475
sandeepjasuja@gmail.com
Dr Sadanand Madhav Karandikar
Ruby Hall Clinic , Pune
Ruby Hall Clinic, Room No-01, 3rd floor, Cancer building, 40, Sassoon Road, Pune-411001, Maharashtra India. Pune MAHARASHTRA
0091-9890281963
skaran44@gmail.com
Dr Patil Tushar Vishvarao
Sahyadri Clinical Research and Development Centre
33/34 B Makarand Bhave Path, Karve Road, Pune 411004, Maharashtra, India
Pune MAHARASHTRA
0091-9552522556
tussipats@hotmail.com
Dr Shailesh Bondarde
Shatabdi Hospital,
Shatabdi Hospital, Suyojit city centre, opp. Mahamarg bus stand, Mumbai naka nashik-422005 Maharashtra, India Nashik MAHARASHTRA
9822012427
shaileshbondarde1971@gmail.com
Dr K C Lakshmaiah
Srinivasam Cancer Care Multispeciality Hospitals India Pvt. Ltd
No.36, 1st Main Road, 5th Cross Nethravathi Street, Maruthi Nagar, Nagarbhavi Main Road, Bangalore-560072 Karnataka, India Bangalore KARNATAKA
9448055949
kcluck@gmail.com
Dr Sushmita Rath
Tata Memorial Hospital
Room No. 1109, 11th floor, Homi Bhabha Block, Tata Memorial Centre, Dr. Ernest Borges Marg, Parel (E) Mumbai-400012, Maharashtra, India Mumbai MAHARASHTRA
9869154396
sushmitarath73@gmail.com
Dr Subramanian Sundaram
V.S Hospital
No.13, East Spur Tank Road, Chetpet, Chennai- 600031 Tami Nadu, India Chennai TAMIL NADU
Artemis Health Sciences-Institutional Ethics committee Artemis Hospital Sector 51 Gurgaon 122001 Haryana, India
Approved
Clinical Research Ethics Committee Medica Superspecialty Hospital 127, Mukundapur, E.M. Bypass, Kolkata- 700099, West Bengal, India
Approved
Dr. GVN Cancer Institute – Institutional Ethics Committee, No.46, Singarathope, Trichy – 620008, Tamil Nadu, India.
Approved
Ethics Committee Netaji Subhas Chandra Bose Cancer Research Institute, 3081, Nayabad, New Garia, Kolkata-700094 India.
No Objection Certificate
Ethics Committee, SMS Medical College and Attached Hospitals, JLN Marg, Jaipur-302004, Rajasthan, India
Approved
Ethics Committee- V.S Hospital 13, East Spur Tank Road, Chetpet, Chennai- 600031 Tami Nadu, India
Approved
Ethics Committee-S P Medical College and AG of Hospitals, Bikaner 334003, Rajasthan, India.
Submittted/Under Review
HCG Central Ethics Committee Healthcare Global Enterprises Ltd., HCG Bangalore Institute of Oncology #8, HCG Towers I, First Floor, P. Kalinga Rao Road, Sampangiram Nagar, Bangalore-560027, Karnataka, India
Approved
HCG Curie City Cancer Centre, Institutional Ethics Committee, #33-25-33,Venkata Krishnayya, Street, Suryaraopet, Vijayawada-520002, Andhra Pradesh, India
Approved
HCG-NCHRI Cancer Center- Central Ethics Committee, 11 Shankar Nagar WHC Road Nagpur-440010 Maharashtra India
Approved
Instituional Ethics Committee MNJ Institute of Oncology and Regional Cancer Centre , Redhills, Hyderabad, Telangana 500004
Approved
Institutional Ethics Committee Basavatarakam Indo American Cancer Hospital & Research Institute, Road No 10, Banjara Hills, Hyderabad,Telangana 500034
Approved
Institutional Ethics Committee N.R.S Medical College & Hospital, 138, Acharya Jagadish Chandra Bose Road, Sealdah, Kolkata, West Bengal 700014, India
Approved
Institutional Ethics Committee Poona Medical Research Foundation E4-C to E4-F , 4th Floor, Fifth ,Avenue, Condominium, Dhole Patil Road, Pune-411001, Maharashtra, India
Approved
Institutional Ethics Committee Shree Himalaya Hospital & Research Institute 4, Vinod Baug, B/h. Railway Station , Jetalpur Bridge, Alkapuri, Vadodra-390007, Gujarat, India
Approved
Institutional Ethics Committee, Deep Hospital, 478-L, Model Town, Ludhiana-141002, Punjab, India
Approved
Institutional Ethics Committee, KLES Dr Prabhakar Kore Hospital and Medical Research center, Nehru Nagar, Belgaum -590010, Karnataka, India
Approved
Institutional Ethics Committee, TATA Memorial Hospital, Dr. E. Borges Marg, Parel, Mumbai-400012
Approved
Institutional Ethics Committee- Apollo Hospitals, Apollo Hospitals Enterprise limited 21 Greams Lane, Off Greams Road Chennai-600006, Tamil Nadu, India
Submittted/Under Review
Institutional Ethics Committee- Bhagwan Mahaveer Cancer Hospital & Research Centre Jawahar Lal Nehru Marg, Jaipur -302017, Rajasthan, India
Submittted/Under Review
Institutional Ethics Committee- Lata Mangeshkar Medical Foundation’s Deenanath Mangeshkar Hospital & Research Center, Erandawane, Pune -411004, Maharashtra, India
Approved
Institutional Ethics Committee- Meenakshi Mission Hospital and Research Centre, Lake Area , Melur Road, Madurai-625 107 , Tamilnadu , India
Approved
Institutional Ethics Committee-Office of Research Cell, Administrative Block King George’s Medical University Lucknow- 226003, Uttar Pradesh, India
Approved
Institutional Ethics Committee-Room no 14, Ground Floor, C-Block, Emergency Department G. Kuppuswamy Naidu Memorial Hospital., Post Box No. 6327, Nethaji Road, Pappanaickenapalayam, Coimbatore – 641037, Tamil Naidu, India
Approved
Life Point Research-Ethics Committee, Life Point Multispecialty Hospital Pvt. Ltd., 145/1, Mumbai – Bangalore Highway, Near Hotel Sayaji, Wakad,Pune-411057, Maharashtra, India
Approved
Magna-Care Ethics Committee C/o Chopda Medicare & Research Center Pvt Ltd, Magnum Heart Institute, Patil Lane No. 1, Laxmi Nagar, Near K.B.H. Vidyalaya, Canada corner, Nashik-422005, Maharashtra, India
Approved
MAHE Ethics Committee Mezzanine Floor, KMC Old Library Building Madhava Nagar Manipal-576104, Karnataka
Approved
Manavata Clinical Research Institute Ethics Committee, Opp. Mahamarg Bus Stand, Mumbai Naka, Nashik-422004, Maharashtra, India
Approved
Sahyadri Hospitals Ltd Ethics Committee Sahyadri Clinical Research and Development Center 33/34 B Makarand Bhave Path, Karve Road, Pune 411004, Maharashtra, India
Approved
SCCMH - Institutional Ethics Committee, #36, 1st Main Road, 5th Cross, Nethravati Street, Maruthi Nagar, Nagarbhavi Main Road, Banglore 560072 Karnataka, India
Approved
Shatabdi Hospital Ethics Committee, Suyojit City Centre, Opp. Mahamarg Bus Stand, Mumbai Naka, Nashik-422005
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Herceptin (Roche)
All participants will receive epirubicin at 75 mg/m2 plus cycloposphamide 600 mg/m2 on Day 1 of each cycle for a total of 4 cycles. Epirubicin and cyclophosphamide are standard chemotherapy drugs used to treat breast cancer. Then, from Cycle 5 to Cycle 8, participant will receive Herceptin® plus paclitaxel. The first time you receive Herceptin® the dose will be 8 mg/kg. Then at subsequent times the dose of Herceptin® will be 6 mg/kg. Paclitaxel dose will be 175 mg/m2 for all doses. Participant will receive Herceptin® plus paclitaxel on Day 1 of each cycle for a total of 4 cycles (Cycles 5-8).Herceptin will be administered in combination with paclitaxel,and Loading dose of 8 mg/kg over 90 min on day 1 followed by 6 mg/kg over 30-90 min every 3 weekly maintenance dose.
Intervention
TX05
Participant will receive TX05 (biosimilar of Trastuzumab) during 8 cycles (a cycle is a period of 3 weeks).
All participants will receive epirubicin at 75 mg/m2 plus cycloposphamide 600 mg/m2 on Day 1 of each cycle for a total of 4 cycles. Epirubicin and cyclophosphamide are standard chemotherapy drugs used to treat breast cancer.
Then, from Cycle 5 to Cycle 8, participant will receive TX05 (depending on the group), and paclitaxel.TX05 will be
administered in combination
with paclitaxel, at an initial dose of 8 mg/kg followed by
subsequent once every three
weeks, dose of 6 mg/kg i.v
.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Female
Details
1. Signed written informed consent.
2. Females ≥ 18 years of age.
3. Histologically confirmed HER2 overexpressing invasive primary operable Stage II/IIIa breast cancer by
American Joint Committee on Cancer 7th Edition staging criteria. Tumor tissue sample must be available
for central analysis.
4. Planned surgical resection of breast tumor (lumpectomy or mastectomy, and SN biopsy or ALND).
5. Planned neoadjuvant chemotherapy.
6. HER2 overexpression as assessed by:
- Gene amplification by fluorescent in-situ hybridization (FISH), chromogenic in-situ hybridization
(CISH), or dual in-situ hybridization (DISH) (as defined by the manufacturer’s kit instruction); OR
- Overexpression by immunohistochemistry (IHC) categorized as IHC 3+; OR
- Overexpression by immunohistochemistry categorized as IHC2+ with FISH, CISH, or DISH
confirmation.
7. Ipsilateral, measurable tumor longest diameter > 2 cm.
8. Known estrogen receptor (ER) and progesterone receptor (PR) hormone status prior to randomization. If
ER/PR status is not available locally, testing may be performed by central laboratory during Screening.
9. ECOG performance status of 0 or 1.
10. Adequate bone marrow, hepatic, and renal functions as evidenced by the following:
- Absolute neutrophils count ≥ 1,500/μL
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 100,000/μL
- Creatinine clearance ≥ 40 mL/min
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine
aminotransferase (serum glutamic pyruvic transaminase) ≤ 2.5 x ULN
- Alkaline phosphatase ≤ 5 x ULN
11. LVEF ≥ 50% or within the normal level of the institution, as assessed by echocardiography or MUGA scan.
12. Able to comply with the study protocol.
13. Female subjects of childbearing potential must have a negative serum pregnancy test within 1 week of first
administration of study drug and agree to use effective contraception (hormonal contraceptive, intrauterine
device, diaphragm with spermicide, or condom with spermicide) throughout the study period and for
6 months after last administration of study drug.
ExclusionCriteria
Details
1. Participation in any interventional clinical study or having taken any investigational therapy during the
2 month period immediately preceding administration of the first dose of study drug.
2. Bilateral breast cancer.
3. Inflammatory breast cancer.
4. Metastases.
5. Previous chemotherapy, biologic therapy, radiation, or surgery for any active malignancy, including breast
cancer.
6. Subjects with one or more of the following conditions:
- Cardiac insufficiency (New York Heart Association III or IV); myocardial infarction,
coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident, unstable
angina pectoris, uncontrolled arrhythmia, or pulmonary embolus within the previous 12 months prior to
the first administration of study drug.
- Clinically significant active infection.
- Poorly controlled diabetes mellitus.
- Uncontrolled hypertension (blood pressure > 150/100 mmHg despite optimal medical therapy).
- Major surgery, significant traumatic injury, or radiation therapy within 4 weeks of first administration
of study drug.
- Grade 3 hemorrhage within 4 weeks of first administration of study drug.
7. Pre-existing clinically significant (≥ Grade 2) peripheral neuropathy.
8. History of malignancy within the last 5 years, except adequately excised squamous or basal cell carcinoma
of the skin, cervical carcinoma in situ, and superficial bladder cancer.
9. Severe dyspnea at rest requiring supplementary oxygen therapy.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
To demonstrate the therapeutic equivalence of TX05(biosimilar of Trastuzumab) to Herceptin based on the pCR rate following neoadjuvant chemotherapy,defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy
(ypT0/Tis ypN0), in subjects with human epidermal growth factor receptor positive (HER2+) invasive early
breast cancer.
The study will consist of a Screening period (Days -28 to 0), and 8 cycles of neoadjuvant treatment (Week 0 [Day 1] to Week 24), followed by surgery (3 to 7 weeks from the 1st day of the last cycle/last dose of study drug).
Secondary Outcome
Outcome
TimePoints
To compare objective response rate (ORR) between the 2 treatment arms;immunogenicity, safety, and tolerability will also be assessed.
ORR, according to RECIST version 1.1, as assessed by the
investigator.
Target Sample Size
Total Sample Size="800" Sample Size from India="150" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a randomized, double-blinded, parallel group, equivalence, multicenter Phase III study. The purpose of this study is to compare the research medicine TX05 with the medicine Herceptin® on how effective they are and how well are tolerated, to find out which one is better for treating HER2+ EBC. TX05 has been designed to be a “biosimilar productâ€, which means, TX05 has the same active ingredient as Herceptin®. The active ingredient is called trastuzumab, which blocks HER2 protein. Thus, similar effects as Herceptin® are expected in patients taking TX05. However this has not yet been proven. The study will also measure the amount of TX05 or Herceptin® in your body and whether or not your body makes antibodies against TX05 or Herceptin®. Antibodies against TX05 could reduce the amount of the TX05 in the blood and its effects on your cancer. Herceptin® is approved for use by Drugs Controller General of India (DCGI), the health authority that gives approval for new medicines to be prescribed in India.