CTRI/2022/03/041271 [Registered on: 22/03/2022] Trial Registered Prospectively
Last Modified On:
25/10/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group Trial
Public Title of Study
Safety, Efficacy, Pharmacokinetics, and Immunogenicity of Test Pertuzumab (ZRC-3277, Cadila Healthcare Ltd.,)
Scientific Title of Study
A Prospective, Randomized, Multicenter, Comparative, Double-blind, Parallel study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Immunogenicity of Test Pertuzumab (ZRC-3277, Cadila Healthcare Ltd.,) with Reference Pertuzumab (Perjeta®, Genentech Inc.,) in Previously Untreated Patients with HER2 Positive Metastatic Breast Cancer.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
PERT.21.001, Version No: 2.0,19.08.2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Maulik Doshi MD DM
Designation
General Manager
Affiliation
Zydus Research Centre
Address
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A Moraiya,
Ahmadabad GUJARAT 382213 India
Phone
02717665555
Fax
Email
maulik.doshi@zyduscadila.com
Details of Contact Person Scientific Query
Name
Dr Sandip Barvaliya MD
Designation
Manager
Affiliation
Zydus Research Centre
Address
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A Moraiya,
Ahmadabad GUJARAT 382213 India
Phone
02717665555
Fax
Email
Sandipkumar.Barvaliya@Zyduscadila.com
Details of Contact Person Public Query
Name
Dr Sandip Barvaliya MD
Designation
Manager
Affiliation
Zydus Research Centre
Address
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A Moraiya,
Ahmadabad GUJARAT 382213 India
Phone
02717665555
Fax
Email
Sandipkumar.Barvaliya@Zyduscadila.com
Source of Monetary or Material Support
Cadila Healthcare Ltd.,,
Zydus Research Center,
Survey No. 396/403,
Sarkhej-Bavla National Highway No.8A Moraiya,
Ahmedabad – 382213
Primary Sponsor
Name
Zydus Research Centre Cadila Healthcare Limited
Address
Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova Petrochemicals, Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad-382213 Gujarat, India
Department of Radiation Oncology, State Cancer Institute, Sheikhpura, Patna, Bihar 800014
Patna BIHAR
9431186988 06122297225 Drricha.madhwi@yahoo.in
Dr Priya Priyadarshini Nayak
Institute of Medical Sciences and SUM Hospital
K-8, Kalinga Nagar, Ghatikia, Bhubaneswar-751003, Odisha, India
Khordha ORISSA
9717122631
drpriya.sjh@gmail.com
Dr Aloke Ghosh Dastidar
Institute of Post-Graduate Medical Education & Research
SSKM Hospital, 244, Acharya Jagadish Chandra Bose Road, Kolkata-700020, West Bengal Kolkata WEST BENGAL
9477095836
alokeghoshdastidar@yahoo.com
Dr Prakash SS
K.R. Hospital, Mysore Medical College & Research Institute
Dept. of Surgical Oncology, Clinical Research Room, Next to Radiology Dept. K.R. Hospital, Mysore Medical College & Research Institute, Irwin Road, Mysore-570001, Karnataka, India Mysore KARNATAKA
99, Kanteerava Studio Main Road, Krishnanadada Nagar, Yeswanthpur, Bengaluru, Karnataka-560096, India
Bangalore KARNATAKA
9880462912
dr.yathish@hotmail.com
Dr Saurabh Prasad
Kingsway Hospitals
"
44, Kingsway, Near Kasturchand Park, Nagpur-440001, Maharashtra, India
"
Nagpur MAHARASHTRA
7066580511
drsaurabhprasad@gmail.com
Dr Maheshkumar Veeranna Kalloli
KLES Dr Prabhakar Kore Hospital and MRC SMO
Second Floor, Nehru Nagar, Belagavi- 590010 Karnataka, India
Belgaum KARNATAKA
9945014996 0831493099 Mahaesh.Kalloli@gmail.com
Dr P K Chaithanya
MNJ Institute of Oncology & Regional Cancer Center
Dept. of Medical Oncology, Red Hills, Hyderabad-500004, Telangana, India
Hyderabad TELANGANA
9581137115
mnjiorccchaithanya@gmail.com
Dr Rushabh Kothari
Narayana Multispecialty Hospital
Unit of Narayana Hrudayalaya Limited Opp. Police Station, Rakhiyal Cross Road, Ahmedabad-380023 Ahmadabad GUJARAT
9167196692
rushabhkothari13@yahoo.com
Dr Gaurav Prakash
Nehru Hospital, Post Graduate Institute of Medical Education and Research (PGIMER)
Department of Hematology and Bone Marrow Transplant, Nehru Hospital, Post Graduate Institute of Medical Education and Research (PGIMER) Sector 12, Chandigarh 160012, India
Chandigarh CHANDIGARH
9914209678
dr.gp04@gmail.com
Dr Srikrishna Mandal
Nil Ratan Medical College and Hospital
"
138, Acharya Jagadish Chandra Bose Road,
Kolkata-700014, West Bengal, India
"
Kolkata WEST BENGAL
9830648931
mondal_srikrishna@rediffmail.com
DrRachan Shetty
Omega Hospital
Mahaveer circle ,
Kankanady, Mangalore,
Karnataka- 575002 Dakshina Kannada KARNATAKA
Srinivasam Cancer Care multispeciality hospital India pvt. ltd.
No. 36. 1st A main 5th cross nethravathi street, Maruthi Nagar , Nagar bhavi main road, Bangalore karnataka - 560072
Bangalore KARNATAKA
9448055949
kcluck@gmail.com
Dr Anil Goel
SSG Hospital
Medical College Department of Radiation Oncology, Baroda, Vadodra-390001, Gujarat India
Vadodara GUJARAT
9227132025
goelanil36@yahoo.com
Dr Sudeep Gupta
TATA MEMORIAL HOSPITAL
Room No: 1109, 11th Floor, Homi Bhabha Block, Tata Memorial Hospital, Tata Memorial Centre, Dr. Ernest Borges Marg, Parel, Mumbai-400012, Maharashtra, India
Mumbai MAHARASHTRA
"Institutional Ethics Committee, HCG Multispeciality hospital, 1139, sir pattani road, Nr. Meghani circle, Bhavnagar, Gujarat- 364001 "
Approved
"Institutional Ethics Committee-I, 3rd Floor, Main Building, Tata Memorial Hospital, , Dr. Ernest Borges Marg, Parel, Mumbai-400012, Maharashtra, India "
Approved
"Institutional Review Board Rajiv Gandhi Cancer Institute and Research Centre Sector 5, Rohini, Delhi 110085, India "
Approved
"Kingsway Hospitals Ethics Committee Kingsway Hospitals, 44, Parwana Bhavan, Near Kasturchand Park, Nagpur-440001, Maharashtra, India "
Approved
"Manavata Clinical Research Insititute Committee, HCG Manavata Cancer Centre, Behind Shivang Auto, Mumbai Naka, Nashik 422002 "
Approved
"MNJ Institute of Oncology & Regional Cancer Center Ethics Committee, MNJ Institute of Oncology & Regional Cancer Center, Dept. of Medical Oncology, Red Hills, Hyderabad-500004, Telangana, India "
"Pranav Diabetes Center Ethics Committee 57/1, Nanda Complex Rammurthynagar Main Road, Banaswadi Bangalore Bengaluru (Bangalore) Urban, Karnataka -560043,India "
Approved
"S C C M H Institutional Ethics Committee, Srinivasam Cancer Care multispeciality hospital India pvt. ltd., No. 36. 1st A main 5th cross nethravathi street, Maruthi Nagar , Nagar bhavi main road, Bangalore karnataka - 560072 "
Ethics committee, 138, Acharya Jagadish Chandra Bose Road, Kolkata-700014, West Bengal, India
Approved
Ethics committee, Unique Hospital Multispeciality & Research Insititue, Nr. Kiran motors, opp. Unique B.R.T.S junction, Civil Hospital char rasta, Sosyo circle lane, off ring road, Surat
Approved
Global Ethics Committee, Room no 110, Global Hospital 4th Floor, Global Point, Beside Nr. Navjivan Restaurant , Sarthana Jakat Naka, Surat - 395006, Gujarat, India
Approved
HCC Vadodara Ethics Committee, Opp. Satsana party plot, Sun pharma road Vadodra, Guajarat-390012
Approved
HCG Central Ethics Committee
Approved
Insititutional Ethics Committee for Human Research, Medical College, Baroda, Anandpura, Vadodra, Gujarat-390001, India
Approved
Institute Ethics Committee, AIIMS Old OT Block, Room No. 102, AIIMS Hospital, Ansari Nagar, New Delhi -110029, India
Approved
Institute of Post-Graduate Medical Education & Research, Research Oversight Committee, Institute of Post-Graduate Medical Education & Research, SSKM Hospital, 244, Acharya Jagadish Chandra Bose Road, Kolkata-700020, West Bengal
Approved
Institution Ethics Committee, SMS Medical College and Attached Hospitals, JLN Marg, Jaipur-302004, Rajasthan, India
Approved
Institutional ethics committee AIIMS Jodhpur, Room No.3032 Research Section Third Floor Medical College Building AIIMS Jodhpur, Rajasthan 342005, India
Approved
Institutional Ethics Committee Bhagwan Mahaveer Cancer Hospital & Research Centre, Jawahar Lal Nehru Marg, Jaipur-302017, Rajasthan, India
Approved
Institutional Ethics Committee Mysore Medical College & Research Institute & Associated Hospitals, Mysore Medical College & Research Institute, Irwin Road, Mysore-570001, Karnataka India
Approved
Institutional Ethics Committee of Oncoville Cancer Hospital & Research Centre No. 4,80 Ft. Road, 7th Block, Nagarbhavi 2nd Stage, Bangalore-560072, Karnataka, India
Approved
Institutional Ethics Committee R.G.Kar Medical College & Hospital, Platinum Jubilee Building, 2nd Floor, 1,Khudiram Bose Sarani, Kolkata-700004, West Bengal
Approved
Institutional Ethics Committee Ruby General Hospital 576, Anandapur main road, Golpark, Sector 1, Kalba, Kolkata, West Bengal- 700107
Approved
Institutional Ethics Committee Saroj Gupta Cancer Centre & Research Institute, MG Road, Thakurpukur, Kolkata-700063, West Bengal, India
Approved
Institutional Ethics Committee, Basavatarakam Indo American Cancer Hospital & Research Institute, Department of Medical Oncology, Road No 10, Banjara hills, Hyderabad- 500034, Telangana, India
Approved
Institutional Ethics Committee, Department of Pharmacology, Government Medical College and Hospital, Medical Square, Nagpur- 440003, Nagpur, Maharashtra, India
Approved
Institutional ethics committee, VMMC & Safdarjung Hospital, New Delhi- 110029, India
Approved
Institutional Ethics Committee, CARE Hospital, Room No.401, 4th Floor, CARE Hospitals, Road No.1, Banjara Hills, Hyderbad-500034, Telangana, India
Approved
Institutional Ethics Committee, Indira Gandhi Institute of Medical Sciences, Sheikhpura, Patna, Bihar 800014, India
Approved
Institutional Ethics Committee, KAHER KLES Dr Prabhakar Kore Hospital and MRC Nehru Nagar, Belagavi -590010 Karnataka, India
Approved
Institutional Ethics Committee, Wockhardt Hospital Limited Nagpur, 1643, Shankar Nagar North Ambazari Road, Nagpur- 440033, Maharashtra, India
Approved
Institutional Ethics Committee- HCG Curie City Cancer, 44-1-1/3, Padavalarevu, Gunadala, Vijaywada-520004, Andhra Pradesh, India.
Sahyadri Hospitals Pvt Ltd Ethics Committee, Sahyadri Clinical Research and Development Center 33/34B Makaranda, Bhave Path, Karve Road Pune -411038, Maharashtra, India
Approved
SANGINI HOSPITAL ETHICS COMMITTEE , C/O Sangini Hospital, First Floor, Santorini Square, B/h Abhishree Complex, Opp. Star Bazar Lane, Satellite, Ahmedabad-380015, Gujarat
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
Pertuzumab
(Perjeta®), Genentech Inc.
1)Route: Intravenous 2)Frequency: every 3 weeks for 6 cycles
Pertuzumab in combination with Trastuzumab and Docetaxel will
be administered
Intervention
Pertuzumab (ZRC-3277, Cadila Healthcare Ltd.,)
1)Route: Intravenous
2)Frequency: every 3 weeks for 6 cycles
Pertuzumab in combination with Trastuzumab and Docetaxel will
be administered
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Female
Details
1.Female patients 18 to 65 years of age (both inclusive).
2.Patient with pathologically (histologically or cytologically) confirmed, adenocarcinoma metastatic breast cancer and
candidate for chemotherapy. Note: Patients with de-novo Stage IV disease are eligible.
3.With at least one measurable metastatic target lesion (based on RECIST criteria, version1.1).
4.Documentation of following prior to randomization:
a)Documentation of HER2 gene amplification by fluorescent in situ hybridization (FISH); as defined by a ratio >2.0) OR
documentation of HER2-overexpression by immunohistochemistry (IHC) (defined as IHC3+, or IHC2+ with FISH confirmation)
(estrogen receptor/progesterone receptor positive subjects may be enrolled if they are HER2 positive) prior to
randomization, see Section 6.4 for detailed criteria)
5. Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1.
6. Left ventricular ejection fraction (LVEF) of ≥ 50% at baseline (within 42 days of randomization) as measured by
echocardiography (ECHO) or multiple gated acquisition (MUGA).
Note: ECHO is the preferred method. If the patient is randomized, the same method of LVEF assessment (i.e., ECHO or MUGA)
must be used throughout the study and it should preferably be obtained at the same institution and preferably by the
same assessor)
7. Patient able to understand and willing to give the informed consent and able to comply with the requirements of the study
protocol.
8. A woman of childbearing potential must have a negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) at
screening and urine β-hCG test at randomization.
9. Woman of child-bearing potential must agree to use adequate contraceptive methods that is highly effective (with a failure
rate of <1% per year), with low user dependency when used consistently and correctly, during the intervention period and for
at least 7 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose
of reproduction during the study and for a period of 7 months. The investigator should evaluate the effectiveness of the
contraceptive method in relationship to the first dose of study intervention.
ExclusionCriteria
Details
1. History of anticancer therapy for MBC, with the exception of single prior hormonal regimen for MBC,
which must be stopped prior to randomization.
Note 1: Anticancer therapy for MBC includes any epidermal growth factor receptor or anti- HER2 agents or
vaccines, cytotoxic chemotherapy, or more than one prior hormonal regimen for MBC
Note 2: Single prior hormonal regimen for MBC may include more than one hormonal therapy.If a patient is
switched to a different hormonal therapy because of disease progression, this will be counted as two
regimens, and the patient will not be eligible for the study. If a patient is switched to a different
hormonal therapy for reasons other than disease progression (e.g., toxicity or local standard practice), this
will be counted as single regimen.
2. History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free
interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of <
12 months.
3. History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment
setting, except trastuzumab used in the neoadjuvant or adjuvant setting.
4. Patients with CNS metastases, except for treated asymptomatic CNS metastases, provided all of the following
criteria are met:
a. Only supra-tentorial metastases allowed (i.e., no metastases to midbrain, pons, medulla, or spinal cord)
b. No evidence of interim progression or hemorrhage after completion of CNS-directed therapy
c. No ongoing requirement for corticosteroids as therapy for CNS disease (anticonvulsants at a stable dose are
allowed)
d. No stereotactic radiation within 14 days or whole-brain radiation within 28 days prior to randomization
e. Leptomeningeal disease (i.e. carcinomatous meningitis)
5. History of persistent Grade ≥ 2 hematologic toxicity resulting from previous neoadjuvant or adjuvant therapy
(all grades based on National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 5.0 [NCI
CTCAE v 5.0]).
6. Current peripheral neuropathy of NCI-CTCAE, Version 5.0, Grade ≥ 3 at randomization.
7. Have a history of congestive heart failure (CHF) of any New York Heart Association (NYHA) criterion, or
serious cardiac arrhythmia requiring treatment (except for atrial fibrillation,paroxysmal supraventricular
tachycardia).
8. History of myocardial infarction within 6 months before randomization.
9. Current uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100
mmHg), or unstable angina.
10. Current dyspnea at rest due to complications of advanced malignancy or other diseases that require
continuous oxygen therapy.
11. History of other malignancy within the previous 5 years, except for carcinoma in situ of the cervix or non-
melanoma skin carcinoma that has been previously treated with curative intent.
12. History of exposure to the following cumulative doses of anthracyclines:
a. doxorubicin or liposomal doxorubicin > 360 mg/m2
b. epirubicin > 720 mg/m2
c. mitoxantrone > 120 mg/m2 and idarubicin > 90 mg/m2
d. Other (e.g., liposomal doxorubicin or other anthracycline > the equivalent of 360 mg/m2 of doxorubicin)
e. If more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360
mg/m2 of doxorubicin.
13. Have received stem-cell support for chemotherapy.
14. Have a history of hypersensitivity to the Pertuzumab or to drugs with similar chemical structures,
or to any of the excipients, or to murine proteins.
15. Have a history of severe hypersensitivity reaction to Trastuzumab and Docetaxel, or to any of the
excipients.
16. Inadequate organ function, evidenced by the following laboratory results within 28 days prior to
randomization:
a. Hemoglobin level < 9 g/dL
b. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels > 3.0 x upper limit of normal (ULN)
(>5 x ULN in patients with liver metastases)
c. AST (SGOT) or ALT (SGPT) > 1.5 × ULN with concurrent serum alkaline phosphatase> 2.5 × ULN (unless bone
metastases are present)
d. Absolute neutrophil count < 1,500 cells/mm3
e. Total serum bilirubin >1.5 x ULN
f. Serum creatinine > 2.0 mg/dL or 177 μmol/L
17. Have received treatment with any other investigational drug in the last 30 days before study entry, or
within less than five half-lives after receiving the previous investigational drug.
18. Receipt of IV antibiotics for infection within 14 days of randomization.
19. Current chronic daily treatment with corticosteroids (dose of > 10 mg/day methylprednisolone
equivalent) (excluding inhaled steroids).
20. History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive,
or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening.
21. History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV
at Screening.
22. Pregnant or a nursing mother.
23. Major surgical procedure or significant traumatic injury within 28 days prior to study treatment
start or anticipation of the need for major surgery during the course of study treatment.
24. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary,
or metabolic disease; wound healing disorders; ulcers; or bone fractures).
25. Have a history or suspicion of unreliability, poor cooperation or non-compliance with medical treatment or
any other medical or psychiatric condition that could compromise study participation.
26. History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th
edition) (DSM-V) criteria within 1 year before Screening or positive test result(s) for alcohol or drugs of
abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines) at
Screening.
27. Have any concurrent disease 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
Pre-numbered or coded identical Containers
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
To compare the objective response rate (ORR) following Test Pertuzumab (Cadila
Healthcare Ltd.,) plus Trastuzumab and Docetaxel versus Reference Pertuzumab (Perjeta®,
Baseline and Cycle 6
Secondary Outcome
Outcome
TimePoints
To assess the pharmacokinetics of Pertuzumab (Test Product, Cadila Healthcare Ltd.,)
compared to Reference Pertuzumab (Perjeta®, a product of Genentech, Inc).
At Pre-dose, end of infusion, 3 h, 6 h, 24 h, 48 h, 96 h, 168 h, 336 h and 504 h from the start of infusion
of cycle 1. Additionally, Pre-dose blood samples will be withdrawn at Day 43, 64, 85, 106 and Day 127 (EOS)
To assess the safety and tolerability of Pertuzumab (Test Product, Cadila Healthcare Ltd.,)
compared to reference Pertuzumab (Perjeta®, a product of Genentech, Inc).
At Baseline, Cycle 1 to Cycle 6 and EOS i.e throughout the study
To assess the immunogenicity of Pertuzumab (Test Product, Cadila Healthcare Ltd.,) compared
to Reference Pertuzumab (Perjeta®, a product of Genentech, Inc.,).
baseline and end of the study i.e Day 1, Day 64, and Day 127
Target Sample Size
Total Sample Size="268" Sample Size from India="268" Final Enrollment numbers achieved (Total)= "268" Final Enrollment numbers achieved (India)="268"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Breast cancer is the second most common cancer worldwide and the fifth cause of death from cancer overall (522,000 deaths) and it is the most frequent cause of cancer death in women in less developed regions.In developed countries between 6 and 10 % of women will have metastatic disease when diagnosed with breast cancer ; in developing countries this percentage can reach 60 %. Depending on initial stage, tumor biology, and type of treatment scheme received, between 30 and 50 % of women with early breast cancer will relapse.
Pertuzumab targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2) and, thereby, blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3, and HER4. As a result, Pertuzumab inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated protein (MAP) kinase, and phosphoinositide 3-kinase (PI3K). Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. In addition, Pertuzumab mediates antibody-dependent cell-mediated cytotoxicity (ADCC).
Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular 286 dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein 287 (HER2). Pertuzumab inhibits ligand-initiated intracellular signaling through two 299 major signal pathways, mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase 300 (PI3K).
Hence we have planned this study which is a Prospective, Randomized, Multicenter, Comparative, Double-blind, Parallel study to Evaluate the Efficacy and Safety of Test Pertuzumab (ZRC-3277, Cadila Healthcare Ltd.,) with Reference Pertuzumab (Perjeta®, Genentech Inc.,) in Previously Untreated Patients with HER2 Positive Metastatic Breast Cancer.