CTRI/2022/12/048133 [Registered on: 14/12/2022] Trial Registered Prospectively
Last Modified On:
28/08/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A study of Pertuzumab in breast cancer patients
Scientific Title of Study
Randomized, Double-Blind, Multicenter, Parallel Group, Clinical Trial to Compare Efficacy, Safety and Immunogenicity of Intas Pertuzumab with Perjeta® (In combination with Trastuzumab and Docetaxel) in Patients with HER2-Positive Metastatic Breast Cancer.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
0375-20, Version No. 1.0, Dated: 01 April 2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Prashant Modi
Designation
Sr. General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Department of Project Management & Regulatory
Affairs, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G.
Highway, Gota
Ahmadabad GUJARAT 382481 India
Phone
07940202375
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Details of Contact Person Scientific Query
Name
Dr Naman Shah
Designation
Sr. General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Department of CTM Medical Services, Plot No.
38,Survey No. 388 Near Silver Oak Club, S. G. Highway, Gota
Ahmadabad GUJARAT 382481 India
Phone
07940202389
Fax
07940202021
Email
namanshah@lambda-cro.com
Details of Contact Person Public Query
Name
Prashant Modi
Designation
Sr. General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Department of Project Management & Regulatory
Affairs, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G.
Highway, Gota
Department of Clinical Research, Room no.NA, Tosham Road, Near South Bypass Crossing Hisar -125005, Haryana Hisar HARYANA
9896539142
drlovenish@gmail.com
Dr Saroj Kumar Das Majumdar
All India Institute of Medical Sciences
Department of Clinical Research,Room no.NA,Sijua, Patrapada, Po- Dumduma, Bhubaneswar- 751019 Odisha Khordha ORISSA
9438884066
sarojmajumdar@gmail.com
Dr Sajjan Rajpurohit
Dr. B L Kapur Memorial Hospital
Department of Clinical Research,Room no.NA,Pusa Road, New Delhi- 110005 Delhi, India New Delhi DELHI
9999660200
sajjanrajpurohit@yahoo.com
Dr K Velavan
Erode Cancer Centre
Department of Clinical Research,Room no.NA,1/393, Velavan Nagar, Perundurai Road, Thindal, Erode- 638012 Erode TAMIL NADU
9842334222
kvel@rediffmail.com
Dr Vijay KumarMahobia
Government Medical College and Hospital
Department of Clinical Research,Room no.NA, Medical Square Road - 440003
Nagpur MAHARASHTRA
9881287465
drvijayct@gmail.com
Dr M Gopichand
HCG City Cancer Centre
Department of Clinical Research,Room no.NA,33-25-33-C4, Venkat Krishnyya Street, Surjerao Peth, Vijaywada- 520002 Andhra Pradesh Krishna ANDHRA PRADESH
9642611888
mgopichand@yahoo.com
Dr Rajnish Nagarkar
HCG Manavta Cancer Center
Department of Clinical Research,Room no.NA,HCG Manavta Cancer Centre, Behind Shivang Auto, Mumbai Naka, Nashik- 422002 Maharashtra Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Abhishek Kakroo
Hemato-oncology Clinic Ahmedabad Pvt Ltd
Department of Clinical Research, Room no.NA, Nirnraya Complex Ground to l-third Floor. Beside Pandit Dindayal Upadhyay Auditorium, Rajpath Club Road, Off S.G. Highway, Ahmedabad-380054, Gujarat Ahmadabad GUJARAT
9974911291
kakrooablrishek@yahoo.com
Dr Niraj Bhatt
Isha Hospital
Department of Clinical Research, Room no.NA, Sarabhai Campus, Sarabhai Main Road Behind , Atlantis Ln, Vadodara, Gujarat - 390007 Vadodara GUJARAT
9925581480
niraj.bhatt@greenashram.org
Dr Ram Krishna
Jaipur National University Institute for Medical Sciences and Research Centre
Department of Clinical Research, Room no.NA, Near New RTO Office, Agra Road, Jagatpura , Jaipur, Rajasthan - 302017 , India. Jaipur RAJASTHAN
7060924809
jnuramkrishna@gmail.com
Dr Vijith Shetty
Justice K S Hegde Charitable Hospital
Department of Clinical Research, Room no.NA, Manglore University Road, Deralakatte , Manglore, Karnataka , India -575018 Bangalore KARNATAKA
8861796017
vshettyonco@gmail.com
Dr K Shilpa
King George Hospital
Department of Clinical Research,Room no.NA,King George Hospital, Maharanipeta, Vishakhapatnam- 530002 Andhra Pradesh Visakhapatnam ANDHRA PRADESH
9440731463
shilpakandipalli@gmail.com
Dr Shanti Prakash Shrivastav
Kiran Hospital Multi Super Speciality Hospital & Research Center
Department of Clinical
Research,Room
no.NA, Near Sumul Dairy 395004 India
Surat GUJARAT
9824196910
communication@kiranhospital.com
Dr Mahesh Kumar Kalloli
KLES Dr Prabhakar Kore Hospital & Medical Research Centre,
Department of Clinical Research,Room no.NA, Nehrunagar- 590010 Belgaum KARNATAKA
9945014336
mahesh.kalloli@gmail.com
Dr Praveena Voonna
Mahatma Gandhi Cancer Hospital & Research Institute
Department of Clinical Research,Room no.NA,1/7, MVP Colony, Vishakhapatnam- 530017 Andhra Pradesh Krishna ANDHRA PRADESH
9502885780
praveena.voonna@gmail.com
Dr Subrata Chatterjee
Medical College & Hospital , Kolkata
Department of Clinical Research, Room no.NA, Medical college & Hospital Kolkata,
Department of Radiotherapy,
88, College Street, Kolkata Medical College Area,
Kolkata, West Bengal – 700073 – India. Kolkata WEST BENGAL
9831143376
chatterjeesubrata@gmail.com
Dr P K Chaithanya
MNJ Institute Of Oncology & Regional Cancer Centre
Department of Clinical Research,Room no.NA,, Red Hills, Hyderabad – 500004, Telangana, India. Hyderabad TELANGANA
8897199994
mnjiorccchaithanya@gmail.com
Dr Chandrashekhar Pethe
Mumbai Oncocare Centre
Department of Clinical Research,Room no.NA,Plot No 4 & 5, 277/1/3, Near Indrayani Lawns, Aurangabad Road, Nashik- 422003 Maharashtra Nashik MAHARASHTRA
8888736446
drcvpethe@mocindia.co.in
Dr Vashista Maniar
Mumbai Oncocare Centre
Department of Clinical Research,Room no.NA,1st Floor, Shreepati, Arcade August Kranti Marag, Nava Chowk, Mumbai- 400036 Maharashtra Mumbai MAHARASHTRA
7167009042
vpm@mocindia.co.in
Dr Rushabh Kothari
Narayana Multispeciality Hospital
Department of Clinical Research, Room no.NA, Unit of Narayana Hrudayalaya Limited, Opp. Police Station, Rakhial Cross Road, Ahmedabad-380023, Gujarat, India. Ahmadabad GUJARAT
9167196692
rushabhkothari13@yahoo.com
Dr Anil MR
Oncoville Cancer Hospital & Research Center
Department of Clinical Research, Room No. 4, 80 Feet Ring Road, 7th Block, Nagarbhavi 2nd Stage, Bangalore- 560072- Karnataka. Bangalore KARNATAKA
9739808502
dranil.onco@gmail.com
Dr Bhushan Tapiram Nemade
Sankalp Speciality Hospital
Department of Clinical Research, Room no.NA, Dhanvantari Marg, Vallabh Nagar, Behind Chhan Hotel, Mumbai, Agra Highway, Mumbai - Naka, Nashik - 422009, Maharashtra, India Nashik MAHARASHTRA
9766126162
drbtnemade@yahoo.co.in
Dr Nirali Trivedi
Shankush Hospitals Pvt. Ltd
Department of Clinical Research,Room no.NA,B/H Divine Child School, Near Shukash Water Park, Ahmedabad- Mehsana Highway, Baliyasan, Mehsana- 382732 Gujarat Mahesana GUJARAT
8980008109
nirali_baxi81@yahoo.com
Dr Alpesh Kikani
Shashwat Haemato Onco Associates
Department of Clinical Research, Room no.NA, 2nd Floor, CIGIS Hospital, Near Balaji Hall, Near 150 feet ring road, Rajkot - 360004, India. Rajkot GUJARAT
9601649096
alpesh.kikani@shashwat.com
Dr Aditi Thanky
Sterling Hospital Unit of Sterling Add life India Pvt Ltd
Department of Clinical Research, Room no.NA, Plot no: 251, 150 feet Ring Road, Nr. Raiya Circle, Rajkot - 360007, Gujarat, India Rajkot GUJARAT
9925025381
aditik2008@Yahoo.com
Dr Rajendra Singh Arora
Sujan Surgical Cancer Hospital & Amravati Cancer Foundation
Department of Clinical Research,Room no.NA,52/B, Shankar Nagar, Main Road, Amravati- 444605 Maharashtra Amravati MAHARASHTRA
9823097573
dr_rsarora@rediffmall.com
Dr Ankit Patel
Sunshine Global Hospital
Department of Clinical Research,Room no.NA,Beside Big Bazar, Dumas-Piplod Road, Surat- 395007 Gujarat, India Surat GUJARAT
9825404202
drankitoncologist@gmail.com
Dr Rakesh Taran
Taran Onco Care (A Unit of Taran Medi Care Pvt. Ltd.)
Department of Clinical Research, Room no.NA, 1, Ravindra Nagar, Near Patrakar Square, Indore – 452018, M.P. India. Indore MADHYA PRADESH
Institutional Ethics Committee, King George Hospital,Dr. K Shilpa
Approved
Institutional Ethics Committee, Sunshine Global Hospital,Dr. Ankit Patel
Approved
Institutional Ethics Committee- Erode Cancer Centre,Dr. K Velavan
Approved
Institutional Review Board Mahatma Gandhi Cancer Hospital & Research Institute, Dr. Praveena Voonna
Approved
Kiran Hospital Ethics Committee, Dr. Shanti Prakash Shrivastav
Approved
Manavata Clinical Research Institute Ethics Committee,Dr. Rajnish Nagarkar
Approved
MNJ Institute of Oncology & Regional Cancer Centre Ethics Committee, Dr. P. K. Chaithanya
Approved
Mumbai Oncocare Centre Institutional Ethics Committee, Dr. Chandrashekhar Pethe
Approved
Mumbai Oncocare Centre Institutional Ethics Committee,Dr. Vashista Maniar
Approved
Navsanjeevani Hospital Ethics Committee, Dr. Bhushan Tapiram Nemade
Approved
Rectitude Ethics Committee DNS Hospital Pvt. Ltd., Dr. Rakesh Taran
Approved
Sangini Hospital Ethics Committee, Dr. Rushabh Kothari
Approved
Sterling Institutional Ethics Committee, Dr. Aditi Thanky
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
Intervention
Intas Pertuzumab
Strength- 420 mg/14 mL single-dose vial; Dosage Form- Injection, solution, concentrate; Route of administration- Intravenous infusion; Dose- 8 mg/kg for Cycle 1, and 6 mg/kg for subsequent cycles; Frequency- every 3 weeks
Comparator Agent
Perjeta
Strength- 420 mg/14 mL single-dose vial; Dosage Form- Injection, solution, concentrate; Route of administration- Intravenous infusion; Dose- 8 mg/kg for Cycle 1, and 6 mg/kg for subsequent cycles; Frequency- every 3 weeks
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Female
Details
1.Study participants must voluntarily provide written informed consent indicating that he or she understands the purpose of, and procedures required for the study and is willing to participate in the study.
2.Female participants must be 18 years and older of age, at the time of signing the informed consent.
3.Participants who are medically stable on the basis of physical examination, medical history, and 12-lead ECG performed at screening. Any abnormalities, must be consistent with the underlying illness in the study population and this determination must be recorded in the participants source documents and initialed by the investigator.
4.Participants who are medically stable on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel including liver enzymes, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participants source documents and initialed by the investigator.
5.Histologically or cytologically confirmed adenocarcinoma of the breast with the following: -Is locally recurrent or metastatic disease, and candidate for systemic chemotherapy
-Is not amenable to resection with curative intent (curative surgery and/or radiation).-With at least one measurable lesion (based on RECIST criteria, version 1.1).Note: Particpants with de-novo Stage IV disease are eligible. Bone and skin lesions, as well as lesions that were irradiated, biopsied or had any form of local intervention or surgical manipulation are only to be assessed as non-target lesions. Baseline imaging scans must have been performed in the 4 weeks preceding randomization.
6.Documentation of HER2 gene amplification by fluorescent in situ hybridization (FISH); as defined by a ratio greater than 2.0) or documentation of HER2-overexpression by immunohistochemistry (IHC) (defined as IHC3 positive, or IHC2 positive with FISH confirmation) as assessed on primary tumor and/or metastatic site as determined in a local laboratory prior to randomization according to American Society of Clinical Oncology – College of American Pathologists (ASCO-CAP) guidelines.
7.Left Ventricular Ejection Fraction (LVEF) greater than or equal to 50 percent at baseline (within 42 days of randomization) as determined by either ECHO or MUGA. History of LVEF decline to below 50 percent during or after prior trastuzumab adjuvant or neo-adjuvant therapy will not be eligible.Note: ECHO is the preferred method. If the participant is randomized, the same method of LVEF assessment, ECHO or MUGA, must be used throughout the study, and to the extent possible, be obtained at the same institution.
8.Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
9.A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
-Is not a woman of childbearing potential (WOCBP)
OR -Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of less than 1percent per year), with low user dependency when used consistently and correctly, as described in Appendix 10.4 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 at least 7 months after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. -A WOCBP must have a negative highly sensitive serum pregnancy test within 14 days and a negative urine pregnancy test within 2 days before the first dose of study intervention.
-If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.-Additional requirements for pregnancy testing during and after study intervention.-The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
ExclusionCriteria
Details
1.History of clinically significant liver or renal insufficiency clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, metabolic disturbances, wound healing disorders, ulcers, or bone fractures as determined by the investigator.
2.Known allergies, hypersensitivity, or intolerance to study drugs or its excipients.
3.History of anticancer therapy for metastatic breast cancer or locally recurrent breast cancer (with the exception of one prior hormonal regimen for MBC).This includes any EGFR or anti-HER2 agents or vaccines, cytotoxic chemotherapy, or more than one prior hormonal regimen for MBC.
Note One prior hormonal regimen for MBC may include more than one hormonal therapy, for example, if the switch is not related to disease progression, such as toxicity or local standard practice, this will be counted as one regimen. If a participant receives hormonal therapy for MBC and is switched to a different hormonal therapy due to disease progression, this will be counted as two regimens and the participant is not eligible.
4.History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab and or or lapatinib used in the neoadjuvant or adjuvant setting.
5.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 within 12 months.
6.History of persistent Grade greater than or equal 2 hematologic toxicity as per NCI-CTCAE, Version 5.0 resulting from previous adjuvant therapy.
7.Current peripheral neuropathy of NCI-CTCAE, Version 5.0, Grade greater than or equal 3 at screening.
8.Current clinical or radiographic evidence of central nervous system metastases. Brain scan at screening or baseline is not mandatory. In case of clinical suspicion brain scan can be performed based on investigator judgment.
9.History of exposure to the following cumulative doses of anthracyclines
-doxorubicin or liposomal doxorubicin greater than 360 mg per m2
-epirubicin greater than 720 mg per m2
-mitoxantrone greater than 120 mg per m2 and idarubicin greater than 90 mg per m2
-Other (e.g., liposomal doxorubicin or other anthracycline greater than the equivalent of 360 mg per m2 of doxorubicin)
-If more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg per m2 of doxorubicin.
10.Current uncontrolled hypertension (systolic greater than 150 mmHg and or or diastolic greater than 100 mmHg).
11.Participant with known history or current symptoms of any of the following clinically significant cardiac conditions within the past 6 months prior to screening
-Unstable angina or myocardial infarction
-New York Heart Association (NYHA) functional classification for cardiac disease of Class II or greater
-High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate greater than or equal to 100 per min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block, such as second degree AV-block Type 2 (Mobitz 2) or third-degree AV-block).-Clinically significant pericardial disease -Electrocardiographic evidence of acute ischemic or active conduction system abnormalities-Any other cardiac illness that could lead to a safety risk to the participant,-Participants with known coronary artery disease, congestive heart failure not meeting the above criteria, must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
12.Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy.
13.Any of the following abnormal investigational values
-General Any laboratory abnormality which, in the opinion of the Investigator, would prevent the participant from safely completing the study or interfere with the interpretation of the study results.
-Absolute neutrophils count less than or equal to 1500 per mm3
-Platelet count less than or equal to 100,000 per mm3
-Hemoglobin less than 9.0 g per dL (With no history of transfusion within the past 2 weeks)
-Serum creatinine greater than 2.0 mg per dL and per or creatinine clearance by Cockroft-Gault formula less than 30 mL per min
-Total bilirubin greater than or equal to 1.5 in to ULN (higher level greater than or equal to 3 in to ULN acceptable for Gilberts Syndrome)
-Aspartate aminotransferase (AST) and or or alanine aminotransferase (ALT) greater than or equal to 2.5 in to ULN. (Greater than or equal 5.0 in to ULN if liver metastases are present).
-International normalized ratio (INR) and activated partial thromboplastin time or partial thromboplastin time (aPTT or PTT) greater than 1.5 in to ULN (unless on therapeutic coagulation)
14.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.
15.Receipt of IV antibiotics for infection within 14 days of randomization.
16.Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
17.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.
18.History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening.
19.History of drug or alcohol abuse within 1 year before Screening.
20.Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years; carcinoma in situ of the cervix; or malignancy, which is considered cured with minimal risk of recurrence.
21.Received an investigational intervention (including investigational live vaccines) or used an invasive investigational medical device within 30 days or 5 half-lives prior to Baseline, whichever is longer, before the signing the consent.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To establish therapeutic equivalence between Intas Pertuzumab versus Perjeta (in combination with Trastuzumab and Docetaxel) in participants with HER2-positive metastatic breast cancer.
To compare the independently assessed Objective Response Rate (i.e., CR plus PR) using Response Evaluation Criteria in Solid Tumours- Revised RECIST guideline (version 1.1) at Week 24.
Secondary Outcome
Outcome
TimePoints
To assess and compare efficacy of Intas Pertuzumab against Perjeta (in combination with Trastuzumab and Docetaxel) in participants with HER2-positive metastatic breast cancer.
Independently assessed clinical activity at Week 24 between treatment arms by measuring.
- Progression-free survival (PFS)
- Overall survival (OS)
- Duration of response (DR)
- Time to treatment failure
-Time to Progression
To compare first dose pharmacokinetics and trough level pharmacokinetics of Intas Pertuzumab and Perjeta in participants with HER2-positive metastatic breast cancer.
- To compare first dose pharmacokinetics of Intas pertuzumab against Perjeta.
-To assess trough level serum concentration of Pertuzumab
To assess and compare safety, tolerability and immunogenicity of Intas Pertuzumab against Perjeta (in combination with Trastuzumab and Docetaxel) in participants with HER2-positive metastatic breast cancer.
- Incidence and titer of anti-drug antibodies over 24 week treatment duration.
- Adverse Events (clinical and laboratory parameters, vital signs, physical examination) over treatment duration.
Target Sample Size
Total Sample Size="214" Sample Size from India="214" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
16/12/2022
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="2" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
NA
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The primary objective of the trial is to demonstrate therapeutic equivalence of Intas pertuzumab with Perjeta with respect to Objective Response Rate (i.e., CR + PR; ORR) from baseline to 24 weeks by using Response Evaluation Criteria in Solid Tumors: Revised RECIST guideline (version 1.1). Rigorous criteria have been incorporated in the design of this therapeutic equivalence trial to properly assess the effect of the interventions on treatment outcome. In general, standardization of criteria, timing of assessments, procedures and interventions have been incorporated in the design of this trial to minimize variation.